Mandell, Douglas and Bennett's principles and practice of infectious diseases

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Mandell, Douglas, and Bennett’s Principles and Practice of INFECTIOUS DISEASES Copyright page Contributors Preface to the Eighth Edition Chapter 1 1 A Molecular Perspective of Microbial Pathogenicity Keywords Diversity of Human-Microbe Relationships Attributes of Microbial Pathogens Clonal Nature of Bacterial Pathogens Genomics and the Evolution of Pathogenicity Regulation of Bacterial Pathogenicity Microbial Pathogens as Intracellular Parasites Subversion of Host Cellular Processes and Immune Defenses Identification and Characterization of Virulence Genes Molecular Microbiology at the Bedside: Pathogen Detection, Pathogen Discovery, and Genomic Profiling Key References References Chapter 2 2 The Human Microbiome of Local Body Sites and Their Unique Biology Keywords Defining the Human Microbiome Human Microbiome as a Complex Ecosystem Composed of Multiple Body Site Habitats and Niches Oral Microbiome Associations Between Oral Microbiota and Disease States Skin and Nasopharynx Airway and Pulmonary Microbiome Gastrointestinal Tract Esophagus Stomach Intestine (Small and Large) Vaginal Microbiome Bacterial Vaginosis: An Example of a Prevalent Variation in the Vaginal Microbiome Group B Streptococcus Alterations in the Vaginal (and Gut) Microbiota during Pregnancy Summary and Future Directions References Chapter 3 3 Prebiotics, Probiotics, and Synbiotics Keywords Issues Regarding the Complexity and Variability of Probiotics Clinical Studies of Probiotics Proposed Mechanisms of Action of Probiotics Potential Adverse Effects of Probiotic Therapy Summary and Future Directions Key References References Chapter 4 4 Innate (General or Nonspecific) Host Defense Mechanisms Keywords Natural Physical Barriers to the Entry of Microorganisms Into the Body Skin Mucous Membranes Respiratory Tract Intestinal Tract Genitourinary Tract Eye Innate Immunity and the Inflammatory Response Chemokines and Chemotaxis Phagocytosis and Autophagy Innate Receptor Families Pathogen Interference with Innate Immune Responses Other Host Factors Impacting the Host-Pathogen Interaction Metabolic Changes Nutrition Aging Stress Hormones Key References References Chapter 5 5 Adaptive Immunity: Keywords Short View Summary Immunoglobulin Structure Basic Antibody Structure F(ab′)2, Fab, and Fc Pieces Antigen Binding, Affinity, and Avidity Immunoglobulin Classes Immunoglobulin M Immunoglobulin G Immunoglobulin A Immunoglobulin D Immunoglobulin E Effector Functions Mediated by Antibodies Blocking or Neutralization Complement Activation Opsonization Antibody-Dependent Cellular Cytotoxicity Kinetics of Antibody Production and Diagnosis of Infections Laboratory Measurement of Antibodies Quantification of Total Immunoglobulin Serum Protein Electrophoresis for Monoclonal Gammopathies Measurement of Functional Antibody Western Blot Agglutination and Complement Fixation Immunofluorescence and Immunohistochemistry Enumeration of Antibody-Producing B Cells: The ELISPOT Assay Assays to Measure Antigen Measurement of Immune Complexes B-Cell Maturation and Immunoglobulin Production DNA Rearrangement and Generation of Diverse Antigen-Binding Sites Deletion of Autoreactive Clones Antigen Stimulation: First Signal Co-receptors Amplify or Suppress Antigen Signaling Second Signals and Interactions between B Cells and T Cells How B Cells Find and Activate T Cells T-Cell–Independent Antigens Downregulation of Antibody Production B1 Cells Antibody-Mediated Pathology Gell and Coombs Classification of Hypersensitivity Responses Type I Hypersensitivity Type II Hypersensitivity Origin of Autoreactive Antibodies Type III Hypersensitivity Hypergammaglobulinemia Immunodeficiencies Immunoglobulin A Deficiency Agammaglobulinemias Hyper-Immunoglobulin M Syndrome Common Variable Immunodeficiency Immunoglobulin G Subclass Deficiencies Selective Immunodeficiencies Combined T-Cell and B-Cell Defects Malignancies Therapeutic Uses of Antibodies Passive Immunization Intravenous Immune Globulin Replacement Monoclonal Antibodies Key References References Chapter 6 6 Cell-Mediated Defense against Infection Keywords T-Cell Subsets and Phenotypic Diversity CD4+ T Cells Th1 Cells Th2 Cells Th17 Cells T-Regulatory Cells Helper T-Follicular Cells Plasticity of Helper T-Cell Subsets In Vivo CD4+ T-Cell Responses to Microbial Infection: Lessons from Mouse Models CD8+ T Cells T-Cell Memory NKT Cells and T Cells with a Restricted TCR Response T-Cell Activation Antigen Presentation to T Lymphocytes Major Histocompatibility Complex Structure and Peptide Binding MHC Class I Structure MHC Class II Structure Mechanisms of Antigen Processing MHC Class I Antigen-Processing Pathway Viral Intervention with the MHC Class I Antigen-Processing Pathway MHC Class I Cross-Priming MHC Class II Antigen-Processing Pathway CD1 CD1 Protein Structure Antigens Presented by CD1 Cell Biology of CD1 Antigen Processing and Loading Innate Immune Recognition: Setting the Stage for T-Cell Responses Molecular Recognition of Microbial Products Toll-like and C-Type Lectin Receptors NOD-like Receptors and the Inflammasome C-Type Lectins and Other Receptors Implicated in Innate Immune Recognition Links between Innate Immune Recognition and Adaptive Immune Responses Antigen-Presenting Cells Microbial Pathogenesis and the Cellular Immune System Viral Infections Intracellular Bacteria Phagosomal Pathogens Cytoplasmic Pathogens Extracellular Bacteria CD1 Antigen Presentation and Host Defense against Infectious Diseases Mycobacteria Major Histocompatibility Complex Immunogenetics Thymic Selection of CD4+ and CD8+ T Cells Lymphoid Anatomy Lymph Nodes Spleen Chemokine-Mediated and Integrin-Mediated Trafficking to Lymphoid Tissues Immune Tissues Associated with Mucosal Surfaces Primer on Basic Immunologic Techniques: Foundation of Immunologic Models Characterizing and Measuring Pathogen-Specific Immunity Acknowledgment Key References References Chapter 7 7 Mucosal Immunity Keywords Specialization of Host Responses in Mucosal Tissues The Challenge Adaptation of Mucosal Immune Responses Induction of Mucosal Immune Responses Epithelial Cell Responses and Immunophysiology Antigen-Presenting Cells Innate Lymphoid Cells Sensing Mucosal Microbiota Sensing Metabolites Discrimination between a “Commensal” and a “Pathogen” Adaptive Immunity to Mucosal Stimulation Immunologic Homeostasis in Mucosal Tissues When Mucosal Responses Go Wrong The Mucosal Host Response Defines Pathogenicity Good Bugs, Bad Bugs, and the Hygiene Hypothesis Mucosal Immunization Role of Mucosal Immunity: Beyond the Mucosa Role of the Microbiota in Homeostatic Networks Conclusions Acknowledgment Key References References Chapter 8 8 Granulocytic Phagocytes Keywords Neutrophils Development Morphologic and Structural Characteristics Homeostasis of the Circulating Neutrophil Population Inflammatory Response Priming Step 1: Neutrophil Recruitment Selectin-Mediated Adhesion and Rolling β2-Integrin-Mediated Cell-Cell Interaction Role of Chemokines in Neutrophil Recruitment Step 2: Phagocytosis Step 3: Fate of the Ingested Microbe Oxidative Burst Degranulation Step 4: Resolution of the Inflammatory Response Microbicidal Mechanisms Intraphagosomal Killing of Microbes Extracellular Microbicidal Activity Neutrophils and Microbial Evasion of Host Defense Eosinophils Key References References Chapter 9 9 Complement and Deficiencies Keywords Complement Synthesis, Catabolism, and Distribution Complement Activation Overview: C3, the Linchpin of the Complement System Generation of the Classical-Pathway C3 Convertase Generation of the Alternative-Pathway C3 Convertase The “Tickover” Model The Properdin-Directed Model Assembly of the Membrane Attack Complex Regulation of Complement Activation Regulation of C1 Activation Regulation of the C3 Convertases Regulation of the Membrane Attack Complex Basis for Discriminating between Host and Microbial Cell Surfaces Complement Receptors Families of Complement Proteins Complement-Mediated Functions Complement and Metabolism Complement and Cancer Complement in Tissue Regeneration and Organogenesis Microbial Interactions with the Complement System Complement Deficiency States Incidence General Aspects of the Molecular Basis for Complement Deficiencies Classical-Pathway Deficiencies Clinical Aspects Immune Disorders Pathophysiologic Roles for Complement in Systemic Lupus Erythematosus. Infectious Diseases Molecular Aspects Mannose-Binding Lectin Pathway Deficiencies Deficiency of Mannose-Binding Protein Clinical Aspects Molecular Aspects Deficiency of Ficolin-3 Deficiencies of Collectin 11 (CL-K1) and MASP-1 Clinical Aspects Molecular Aspects Deficiency of Mannose-Binding Protein–Associated Serine Protease 2 Alternative-Pathway Deficiencies Clinical Aspects Molecular Aspects C3 Deficiency Clinical Aspects Molecular Aspects Late Complement Component Deficiencies Clinical Aspects Meningococcal Disease in Complement Deficiency Molecular Aspects Deficiencies of Complement Regulatory Proteins Hereditary Angioedema: C1 Inhibitor Deficiency Factor H Deficiency Clinical Aspects: Membranoproliferative Glomerulonephritis Type II Clinical Aspects: Atypical Hemolytic-Uremic Syndrome Clinical Aspects: Age-Related Macular Degeneration CD59 Deficiency: Paroxysmal Nocturnal Hemoglobinuria Complement in Disease States Infectious Diseases Rheumatologic Disorders Renal Disorders Evaluation and Treatment of Complement Disorders Evaluation Treatment Key References References Chapter 10 10 Human Genetics and Infection Keywords Magnitude of the Host Genetic Effect Approaches Diseases Malaria Mycobacterial Diseases Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome Persistent Hepatitis Other Diseases Specific Susceptibility and Resistance Genes Blood Groups Hemoglobin Gene Variants Glucose-6-Phosphate Dehydrogenase Deficiency Human Leukocyte Antigens Cytokine Genes Chemokine Receptors Mannose-Binding Lectin Toll-Like Receptor Pathway Genes Other Genes Evolutionary Perspective Applications Key References References Chapter 11 11 Nutrition, Immunity, and Infection Keywords Epidemiology of Malnutrition Malnutrition and Immune Function Specific Nutrients and Their Roles in Immunity Fat-Soluble Vitamins Vitamin A Vitamin D Vitamin E Water-Soluble Vitamins Vitamin C Vitamin B6 Folate Vitamin B12 Trace Metals Zinc Selenium Iron Fatty Acids Overnutrition: Obesity and Infectious Diseases Special Populations: Clinical Trials of Nutritional Supplementation to Reduce Infection Risk Surgical and Critically Ill Patients Total Parenteral Nutrition versus Enteral Nutrition* Immunonutrition Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Strategies to Combat Weight Loss and Wasting Associated with Human Immunodeficiency Virus Macronutrient Supplementation Micronutrient Supplementation Older Adults Nutritional Supplements in Older Adults: Effects on Immunity and Clinical Outcomes Multivitamin and Trace Mineral Supplements Vitamin E Zinc Host Nutritional Status and Pathogen Virulence Key References References Chapter 12 12 Evaluation of the Patient with Suspected Immunodeficiency Keywords Index of Suspicion Initial Evaluation Lymphocyte Immune Defects T Cells and Cell-Mediated Immunity B Cells and Humoral Immunity Phagocyte Immune Defects: Neutrophils Neutropenia Chédiak-Higashi Syndrome Leukocyte Adhesion Deficiency Neutrophil-Specific Granule Deficiency Myeloperoxidase Deficiency Chronic Granulomatous Disease Defects Affecting Phagocyte Signaling Phagocyte and Lymphocyte Defects Affecting Mononuclear Cells Hyperimmunoglobulin E–Recurrent Infection Syndrome (Job’s Syndrome) GATA2 Deficiency Complement-Mediated Immunity Acquired Immune Deficiencies Key References References Chapter 13 13 Epidemiologic Principles Keywords Epidemiologic Study Methods Goals of Epidemiologic Analysis Defining Infections, Diseases, and Populations Biology and Statistics Determining Epidemiologic Methods Appropriate to the Study Setting Types of Epidemiologic Studies Observational Studies Disease Surveillance Case Series Case-Control Studies Cohort Studies Cross-Sectional Surveys Outbreak Investigations Experimental Studies Clinical Trials Community Intervention Trials Host-Agent Relationship Agent Host Routes of Transmission Disease Prevention and Control Individual-, Institutional-, Community-, and Global-Based Strategies Assessment of Risk, Feasibility, Cost, and Effectiveness Primary, Secondary, and Tertiary Prevention Primary Prevention Secondary Prevention Tertiary Prevention Key References References Chapter 14 14 Emerging and Reemerging Infectious Disease Threats Keywords Reemerging Vaccine-Preventable Diseases Measles Mumps Pertussis Acute Respiratory Tract Infection Human Metapneumovirus Human Coronaviruses Influenza Avian Influenza Pandemic Influenza H1N1 Variant Influenza A (H3N2) Human Bocaviruses Diarrheal Disease Vector-Borne and Zoonotic Diseases Dengue Chikungunya West Nile Virus Ebola and Marburg Hemorrhagic Fevers Tick-Borne Diseases Antimicrobial Resistance Controlling the Threats Key References References Chapter 15 15 Bioterrorism: Keywords History of Biological Weapons State Actors Non–State Actors Assessing the Threat and Risk of Biological Weapons Pathogens of Greatest Concern Smallpox Anthrax Botulism Glanders and Melioidosis Ebola and Marburg Hemorrhagic Fever Tularemia Epidemic Typhus Plague Event Detection and Epidemiology Event Detection Event Epidemiology Preparing for and Responding to Biological Weapons Before 9/11/2001 After 9/11/2001 Public Health Preparedness and Response Laboratory Systems Biosurveillance Systems Clinician and Health Care System Preparedness and Response Medical Countermeasures Medical Countermeasure Research and Development Strategic National Stockpile Emergency Use Authorization Dual Use: the Two-Edged Sword of Modern Biology Acknowledgment Key References References Chapter 16 16 The Clinician and the Microbiology Laboratory Keywords Specimen Selection, Collection, Transport, and Initial Processing General Considerations Specific Specimen Guidelines and Initial Laboratory Processing Blood Specimens Intravenous Catheter Tips Cerebrospinal, Peritoneal, Pleural, Synovial, and Pericardial Fluids Respiratory Tract Specimens Urinary Tract Specimens Gastrointestinal Tract Specimens Genital Specimens Skin, Skeletal, and Soft Tissue Specimens Detection Methods Microscopy Culture Antigen Detection Nucleic Acid–Based Tests Serology Identification Methods for Bacteria Identification by Biochemical Methods Identification Using Specific Antisera Identification Using Genomic Techniques Identification Using Proteomic Methods Antimicrobial Susceptibility Testing Dilution Methods Agar Diffusion Methods Special Methods Mycobacteria Safety Issues Specimen Collection and Transport Direct Organism Detection Specimen Processing and Plating Significance of Isolation of Mycobacteria from Clinical Specimens Mycobacterial Identification Traditional Categories and Methods Molecular Identification Methods Susceptibility Testing Epidemiology Latent Tuberculosis: Laboratory Diagnosis Aerobic Actinomycetes Specimen Collection and Transport Direct Organism Detection Specimen Processing and Plating Identification of Aerobic Actinomycetes Susceptibility Testing Epidemiology Fungi Terminology Safety Issues Specimen Collection, Transport, and Processing Direct Organism Detection Significance of Isolation of Fungi from Clinical Specimens Identification of Fungi Susceptibility Testing Epidemiology Serology Viruses Virology Specimen Collection and Transport Detection and Identification Methods for Viruses Microscopy Culture Antigen Detection Nucleic Acid–Based Tests Serology Antiviral Susceptibility Testing Parasites Parasitology Specimen Collection and Transport Blood Stool Other Specimens Detection and Identification Methods for Parasites Microscopy Culture Antigen Detection Nucleic Acid–Based Tests Serology References Chapter 17 17 Principles of Anti-infective Therapy Keywords Choice of the Proper Antimicrobial Agent Identification of the Infecting Organism Determination of Antimicrobial Susceptibility of Infecting Organisms Host Factors History of Previous Adverse Reactions to Antimicrobial Agents Age Genetic or Metabolic Abnormalities Pregnancy Renal and Hepatic Function Site of Infection Antimicrobial Combinations In Vitro Results of Combination Therapy Indications for Clinical Use of Antimicrobial Combinations Initial Therapy for Treatment of Critically Ill Patients Polymicrobial Infections Prevention of the Emergence of Resistant Organisms Decreased Toxicity Antimicrobial Synergism Other Agents That Exhibit Synergism Synergism and Infections in Impaired Hosts Combinations Against Fungal Pathogens Disadvantages Associated with Inappropriate Use of Antimicrobial Combinations Antagonism Costs Adverse Effects Dosages and Evaluation of Efficacy Route of Administration Dosing Regimen Therapeutic Drug Monitoring Summary Key References References Chapter 18 18 Molecular Mechanisms of Antibiotic Resistance in Bacteria Keywords Molecular Genetics of Antibiotic Resistance Plasmids Transposable Genetic Elements DNA Integration Elements Mechanisms of Antibiotic Resistance Enzymatic Inhibition β-Lactamases Extended-Spectrum β-Lactamases TEM-Derived. SHV-Derived. CTX-M–Derived. OXA-Derived. AmpC Enzymes. Carbapenemases. Gram-Positive Bacteria Anaerobic Bacteria Contribution of β-Lactamases to β-Lactam Antibiotic Resistance Aminoglycoside Resistance–Modifying Enzymes Chloramphenicol Acetyltransferase Macrolide-, Lincosamide-, Streptogramin-Inactivating Enzymes Tetracycline Inactivation Decreased Permeability of Bacterial Membranes Outer Membrane Permeability Inner Membrane Permeability Promotion of Antibiotic Efflux Tetracyclines Macrolides and Streptogramins β-Lactams Fluoroquinolones Altered Target Sites Alteration of Ribosomal Target Sites Macrolides, Lincosamides, Streptogramins Tetracyclines Aminoglycosides Ketolides Oxazolidinones Alteration of Cell Wall Precursor Targets Alteration of Target Enzymes β-Lactams MRSA Resistance Quinolones Sulfonamides Trimethoprim Protection of Target Site Tetracyclines Fluoroquinolones Overproduction of Target Sulfonamides and Trimethoprim Bypass of Antibiotic Inhibition Resistance to Newer, Older, and Miscellaneous Agents Oxazolidinones Multidrug-Resistance Mechanisms among Bacteria Control of Antibiotic Resistance Key References References Chapter 19 19 Pharmacokinetics and Pharmacodynamics of Anti-infective Agents Keywords Pharmacokinetics Absorption Distribution Metabolism and Biotransformation Elimination Pharmacodynamics Antimicrobial Potency Pharmacodynamic Indices Methodology for Study of Pharmacodynamic Effects of Anti-infective Agents In Vitro Models Animal Models Clinical Trials Concentration-Dependent Killing Agents Time-Dependent Killing Agents Postantibiotic Effect Applied Clinical PK-PD Higher-Dose Extended-Interval Dosing Continuous-Infusion and Extended-Infusion Regimens Dose-Refinement Considerations Antiretroviral Pharmacodynamics Pharmacodynamics for Other Antiviral Drugs Conclusion Key References References Chapter 20 20 Penicillins and β-Lactamase Inhibitors Keywords Penicillins Chemistry Mechanism of Action Bacterial Resistance Classification Pharmacologic Properties Untoward Reactions Clinical Use Prophylactic Use Properties of Individual Penicillins Natural Penicillins Penicillin G Penicillin V Penicillinase-Resistant Penicillins Methicillin Nafcillin Isoxazolyl Penicillins Aminopenicillins Ampicillin Amoxicillin Carboxypenicillins Carbenicillin Ticarcillin Ureidopenicillins β-Lactamase Inhibitors And Inhibitor Combinations Clavulanic Acid Pharmacology Adverse Reactions Amoxicillin-Clavulanate Ticarcillin-Clavulanate Sulbactam Pharmacology Adverse Reactions Clinical Use Tazobactam Pharmacology Adverse Reactions Clinical Use Key References References Chapter 21 21 Cephalosporins Keywords Chemistry Classification Mechanism of Action Spectrum of Activity Mechanisms of Resistance Pharmacologic Properties Adverse Reactions and Toxicities Clinical Uses of Specific Drugs First-Generation Cephalosporins Second-Generation Cephalosporins Third-Generation Cephalosporins Fourth-Generation Cephalosporins MRSA-Active Cephalosporins Cephalosporins Plus β-Lactamase Inhibitors Key References References Chapter 22 22 Other β-Lactam Antibiotics Keywords Carbapenems Chemistry Mechanism of Action Resistance Carbapenem-Resistant Enterobacteriaceae Antibacterial Activity Pharmacology Adverse Reactions Clinical Use Monobactams Key References References Chapter 23 23 Antibiotic Allergy Keywords Pathophysiology Approach to a Patient with an Antibiotic Allergy Information to be Obtained When Taking a History of Antibiotic Allergy Clinical Manifestations Immediate (IgE-Mediated or Pseudoallergic) Drug Reactions Nonimmediate Drug Reactions Drug Rash with Eosinophilia and Systemic Symptoms Diagnosis and Management of Antibiotic Allergy Tests for IgE-Mediated Immediate Reactions Skin Testing: Prick and Intradermal Tests In Vitro Tests Drug Challenge (Drug Provocation Tests) Skin and in Vitro Tests for Nonimmediate Reactions Skin Testing: Delayed Intradermal and Patch Tests In Vitro Tests Procedures to Induce Temporary Drug Tolerance Drug Desensitization Drug Allergy to Specific Antimicrobial Agents β-Lactams Penicillins Epidemiology. Pathophysiology. Clinical Manifestations. Diagnosis. Desensitization. Cephalosporins Pathophysiology. Clinical Manifestations. Diagnosis. Desensitization. Carbapenems Monobactams Cross-Reactivity among β-Lactams Sulfonamides Pathophysiology. Clinical Manifestations. Diagnosis. Treatment. Vancomycin Fluoroquinolones Macrolides Aminoglycosides Multiple Drug Intolerance Syndrome References Chapter 24 24 Fusidic Acid Keywords Short View Summary Structure and Mechanism of Action Antimicrobial Activity Resistance Administration and Dosing Pharmacokinetics and Pharmacodynamics Adverse Reactions Clinical Uses Key References References Chapter 25 25 Aminoglycosides Keywords Short View Summary Chemistry Mechanisms of Action Mechanisms of Resistance Antimicrobial Activity Clinical Pharmacology Nephrotoxicity Experimental Nephrotoxicity Clinical Nephrotoxicity Ototoxicity Cochlear Toxicity Vestibular Toxicity Neuromuscular Blockade Clinical Indications Bacteremia Pneumonia Intra-abdominal Infections Urinary Tract Infections Cystic Fibrosis Prophylaxis Spectinomycin and Gonorrhea Aminoglycosides in Orthopedic Surgery Key References References Chapter 26 26 Tetracyclines, Glycylcyclines, and Chloramphenicol Keywords Short View Summary Tetracyclines Historical Overview and Classification Structure and Mechanism of Action Pharmacology Administration and Dosing Tetracycline Doxycycline Minocycline Absorption and Bioavailability Drug Distribution Drug Elimination Antimicrobial Activity Gram-Positive Bacteria Gram-Negative Bacteria Atypical Bacteria Spirochetes and Rickettsiae Mycobacteria and Nocardia Parasites Clinical Uses General Respiratory Tract Infections Gastrointestinal Tract Infections Genitourinary Tract Infections Spirochetal Infections Malaria Treatment and Chemoprophylaxis Other Infections Acne Vulgaris Anti-inflammatory Uses Bioterrorism Prophylaxis Mechanism of Resistance Adverse Reactions General Gastrointestinal Side Effects Photosensitivity and Hyperpigmentation Teeth and Bone Hepatotoxicity Nephrotoxicity Neurotoxicity Hypersensitivity Reactions Teratogenicity Drug and Food Interactions Glycylcyclines Tigecycline Structure and Mechanism of Action Pharmacology Administration and Dosing Absorption and Bioavailability Drug Distribution Drug Elimination Antimicrobial Activity Gram-Positive Bacteria Gram-Negative Bacteria Anaerobic Bacteria Atypical Bacteria Mycobacteria and Nocardia Clinical Uses Skin and Skin Structure Infections Intra-abdominal Infections Respiratory Tract Infections Other Uses Mechanism of Resistance Adverse Reactions Gastrointestinal Side Effects Hepatotoxicity and Pancreatitis Other Side Effects Increased Mortality Drug Interactions Chloramphenicol Structure and Mechanism of Action Pharmacology Administration and Dosing Absorption and Bioavailability Drug Distribution Drug Elimination Antimicrobial Activity Gram-Positive Bacteria Gram-Negative Bacteria Anaerobic Bacteria Other Organisms Clinical Uses Bacterial Meningitis and Brain Abscess Salmonella Infections Other Infections Mechanism of Resistance Adverse Reactions Hematologic Toxicity Bone Marrow Suppression Aplastic Anemia Gray Baby Syndrome Optic Neuritis and Neurologic Side Effects Other Reactions Drug Interactions Acknowledgment Key References References Chapter 27 27 Rifamycins Keywords Short View Summary Structure and Mechanism of Action Mechanisms of Resistance Antimicrobial Activity Pharmacokinetics Drug Interactions Adverse Drug Reactions Immune-Modulating Effects of Rifampin Rifamycins for the Treatment of Tuberculosis Rifamycins for Treatment of Latent Tuberculosis Infection Rifamycins for Nontuberculous Mycobacterial Infections Mycobacterium leprae Mycobacterium avium- intracellulare Complex Mycobacterium kansasii Other Nontuberculous Mycobacteria Rifamycins for Nontuberculous Mycobacterial Infections Staphylococcal Infections Staphylococcal Biofilms: Foreign-Body Infections and the Role of Rifampin Vancomycin-Intermediate and Vancomycin-Resistant S. aureus and Rifampin Prosthetic Joint Infections Osteomyelitis Central Nervous System Infections Infections Caused by Other Bacteria Streptococcus pneumoniae Enterococci Legionella Rhodococcus Resistant Gram-Negative Bacilli Brucella Bartonella Fungal Infections Second-Line Indications for Rifamycins Chemoprophylaxis Rifaximin: a Selective Gastrointestinal Rifamycin Rifalazil Rifamycins in Development Key References References Chapter 28 28 Metronidazole Keywords History Mechanism of Action Spectrum of Activity Effects on the Human Microbiome Pharmacology Adverse Effects, Contraindications, and Precautions Contraindications Precautions Adverse Effects Mechanisms of Resistance Clinical Uses Parasitic Infections Anaerobic Infections Other Therapeutic Uses Prophylactic Use Drug Interactions and Interference with Laboratory Tests Other Nitroimidazole Antimicrobials Key References References Chapter 29 29 Macrolides, Clindamycin, and Ketolides Keywords Short View Summary Erythromycin Derivation, Chemistry, and Preparations Mechanisms of Action Mechanisms of Resistance Decreased Microbial Entry or Export of Drug Target Site Alterations Drug Inactivation Antimicrobial Activity Other Activities of Erythromycin Clinical Pharmacology Adverse Reactions Drug Interactions Uses of Erythromycin Azithromycin and Clarithromycin Derivation, Chemistry, and Preparations Mechanisms of Action and Resistance Antimicrobial Activity Clinical Pharmacology Adverse Reactions Drug Interactions Uses of Clarithromycin and Azithromycin Ketolides Derivation, Chemistry, and Preparations Mechanisms of Action and Resistance Antimicrobial Activity Clinical Pharmacology Adverse Reactions Drug Interactions Potential Uses for Telithromycin Lincomycin and Clindamycin Derivation, Chemistry, and Preparations Mechanism of Action Mechanisms of Resistance Antimicrobial Activity Clinical Pharmacology Adverse Reactions Drug Interactions Uses of Clindamycin Key References References Chapter 30 30 Glycopeptides (Vancomycin and Teicoplanin), Streptogramins (Quinupristin-Dalfopristin), Lipopeptides (Daptomycin), and Lipoglycopeptides (Telavancin) Keywords Short View Summary Glycopeptides Vancomycin Structure and Mechanism of Action Antimicrobial Activity Mechanisms of Resistance Enterococci Staphylococcus aureus hVISA/VISA. Mechanisms of Decreased Susceptibility to Vancomycin. Laboratory Detection of hIVSA Strains. Clinical Impact of Strains with Increased Vancomycin MIC. VRSA. Coagulase-Negative Staphylococci Other Gram-Positive Bacteria Clinical Pharmacodynamics and Pharmacokinetics Distribution Excretion Administration Dosing in Renal Insufficiency Adverse Reactions Drug Interactions Clinical Uses Skin and Soft Tissue Infections Bacteremia and Endocarditis Meningitis and Ventriculitis Pneumonia Osteomyelitis Pseudomembranous Colitis Febrile Neutropenia Prophylaxis Other Uses Teicoplanin Antimicrobial Activity and Resistance Clinical Pharmacokinetics Adverse Events Clinical Uses Streptogramins Quinupristin-Dalfopristin Mechanism of Action Antimicrobial Activity Resistance Clinical Pharmacodynamics and Pharmacokinetics Distribution and Elimination Administration and Dosing Adverse Events and Drug Interactions Clinical Uses Lipopeptides Daptomycin Mechanism of Action Antimicrobial Activity Resistance CIinical Pharmacokinetics and Pharmacodynamics Distribution and Elimination Pharmacodynamics Drug Dosage and Administration Adverse Reactions and Drug Interactions Clinical Uses Skin and Soft Tissue Infections S. aureus Bacteremia and Endocarditis Staphylococcal Osteoarticular Infections Enterococcal Infections Other Clinical Uses Lipoglycopeptides Telavancin Structure and Mechanism of Action Antimicrobial Activity and Resistance Clinical Pharmacodynamics and Pharmacokinetics Adverse Reactions Clinical Uses Skin and Soft Tissue Infections Hospital-Acquired Pneumonia Dalbavancin Key References References Chapter 31 31 Polymyxins (Polymyxin B and Colistin) Keywords Structure, Source, and Available Preparations Mechanism of Action Antimicrobial Activity Pharmacokinetics Pharmacodynamics Toxicity Clinical Use Key References References Chapter 32 32 Linezolid and Other Oxazolidinones Keywords Short View Summary Chemical Structure Mechanism of Action Antimicrobial Activity Pharmacology Clinical Use Staphylococcus aureus Including MRSA Coagulase-Negative Staphylococci Vancomycin-Resistant Enterococci Streptococci Including Streptococcus pneumoniae Mycobacterial Infections and Nocardiosis Resistance Untoward Reactions Hematologic Toxicities Monoamine Oxidase Inhibition Mitochondrial Toxicity: Neuropathy and Lactic Acidosis Miscellaneous Toxicities Other Oxazolidinones Key References References Chapter 33 33 Sulfonamides and Trimethoprim Keywords Short View Summary Sulfonamides Structure Derivation and Nomenclature Short-Acting or Medium-Acting Sulfonamides Long-Acting Sulfonamides Sulfonamides Limited to the Gastrointestinal Tract Topical Sulfonamides Mechanisms of Action Antimicrobial Activity in Vitro Antimicrobial Resistance Pharmacology Routes of Administration Absorption Distribution Metabolism and Excretion Protein Binding and Blood or Tissue Levels Toxicity and Adverse Reactions Drug Interactions Major Clinical Uses Trimethoprim Structure and Derivation Mechanism of Action Antimicrobial Activity Resistance to Trimethoprim Pharmacology Routes of Administration Distribution Metabolism and Excretion Clinical Use Trimethoprim-Sulfamethoxazole Mechanism of Action and Antimicrobial Activity Trimethoprim-Sulfamethoxazole Resistance Metabolism and Excretion Toxicity and Side Effects Drug Interactions Trimethoprim Plus Other Antimicrobial Agents Clinical Uses of Trimethoprim-Sulfamethoxazole Urinary Tract Infections Respiratory Tract Infections Gastrointestinal Infections Skin and Soft Tissue Infections Sexually Transmitted Diseases Other Infections Pneumocystis jirovecii Infections Prophylactic Use in Immunocompromised Patients Trimethoprim Use in Pregnancy Key References References Chapter 34 34 Quinolones Keywords Short View Summary Chemical Structures Mechanism of Action Mechanisms of Acquired Bacterial Resistance Antimicrobial Activity Pharmacology Absorption Distribution in Tissues Elimination Dosage Adjustments in Renal and Hepatic Insufficiency Interactions with Other Drugs Clinical Uses Urinary Tract Infections Prostatitis Sexually Transmitted Diseases Gastrointestinal and Abdominal Infections Respiratory Tract Infections Bone and Joint Infections Skin and Soft Tissue Infections Other Uses Problems with Quinolone Resistance during Clinical Use Adverse Effects Key References References Chapter 35 35 Unique Antibacterial Agents Keywords Clostridium Difficile Infection LFF571 Surotomycin (CB-183,315) Multidrug-Resistant Bacteria Plazomicin (ACHN-490) Avibactam (NXL104) Omadacycline (PTK 0796) Solithromycin (CEM-101 and OP-1068) Tedizolid (TM-700; Formerly, Torezolid, DA-7157) Conclusion Key References References Chapter 36 36 Urinary Tract Agents: Keywords Short View Summary Nitrofurantoin Mechanisms of Drug Action and Bacterial Resistance Spectrum of Activity Pharmacology Absorption Distribution Excretion Dosing Indications Acute Uncomplicated Cystitis Acute Pyelonephritis and Complicated Urinary Tract Infections Prophylaxis for Recurrent Urinary Tract Infections Adverse Effects Pulmonary Reactions Gastrointestinal Reactions Cutaneous Reactions Hepatic Reactions Hematologic Reactions Peripheral Neuropathy Systemic Inflammatory Response Syndrome Drug Interactions Use in Children and during Pregnancy Fosfomycin Mechanism of Action and Antimicrobial Activity Pharmacology Dosing Indications Acute Uncomplicated Cystitis Adverse Effects Use during Pregnancy Methenamine Mechanism of Action and Antimicrobial Activity Pharmacology Absorption and Distribution Factors Affecting Formaldehyde Concentrations in Urine Acidification of Urine during Methenamine Treatment Dosing Indications Adverse Effects Key References References Chapter 37 37 Topical Antibacterials Keywords Short View Summary General Uses of Topical Antibacterials Skin Disinfection Prophylaxis of Infection in Clean Wounds Prophylaxis of Recurrent Skin and Soft Tissue Infections Prophylaxis of Infection in Operative Wounds Prophylaxis of Vascular Catheter–Related Infections Prophylaxis of Dialysis Catheter Infections Prophylaxis of Health Care–Associated Infections Prophylaxis of Infection in Burn Wounds Treatment of Pyoderma Treatment of Erythrasma and Rosacea Treatment of Acne Vulgaris Elimination of Staphylococcus aureus Nasal Carriage Specific Topical Antibacterials Bacitracin Mechanism of Action. In Vitro Spectrum of Activity. Clinical Uses. Adverse Effects. Neomycin Mechanism of Action. In Vitro Spectrum of Activity. Clinical Uses. Adverse Reactions. Polymyxin B Mechanism of Action. In Vitro Spectrum of Activity. Clinical Uses. Adverse Effects. Mupirocin Structure and Mechanism of Action. In Vitro Spectrum of Activity. Pharmacokinetics. Clinical Uses. Adverse Effects. Key References References Chapter 38 38 Antimycobacterial Agents Keywords Short View Summary First-Line Antituberculous Drugs Isoniazid Derivation and Structure. Mechanism of Action. Antimicrobial Activity and Resistance. Pharmacology. Adverse Reactions Hepatitis. Neurotoxicity. Hypersensitivity Reactions. Miscellaneous Adverse Reactions. Overdose. Significant Drug Interactions. Usage. Availability and Dosage. Rifampin (see also Chapter 27) Derivation and Structure. Mechanism of Action. Antimicrobial Activity and Resistance. Pharmacology. Adverse Reactions. Hepatitis. Effects on Immune Parameters. Hypersensitivity Reactions. Miscellaneous Adverse Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Pyrazinamide Derivation and Structure. Mechanism of Action. Antimicrobial Activity and Resistance. Pharmacology. Adverse Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Ethambutol Derivation and Structure. Mechanism of Action. Antimicrobial Activity and Resistance. Pharmacology. Adverse Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Streptomycin Derivation, Structure, and Pharmacology. Antimicrobial Activity and Resistance. Adverse Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Alternatives to Rifampin Rifabutin Derivation and Pharmacology. Adverse Reactions. Significant Drug Interactions. Usage. Rifapentine Derivation and Pharmacology. Adverse Drug Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Second-Line Antituberculous Drugs Quinolones (see Chapter 34) Mechanism of Action. Antimicrobial Activity and Resistance. Usage. Adverse Reactions. Significant Drug Reactions. Linezolid (see Chapter 32) Capreomycin, Amikacin, and Kanamycin Capreomycin Antimicrobial Activity and Resistance. Adverse Reactions. Significant Drug Interactions. Usage. Availability and Dosage. Amikacin Antimicrobial Activity and Resistance. Adverse Reactions. Usage. Kanamycin Availability and Dosage. Para-aminosalicylic Acid Derivation, Structure, and Pharmacology. Adverse Reactions. Usage. Availability and Dosage. Cycloserine Derivation and Mechanism of Action. Pharmacology. Adverse Reactions. Usage. Availability and Dosage. Ethionamide Derivation, Mechanism of Action, and Resistance. Pharmacology. Adverse Reactions. Usage. Availability and Dosage. β-Lactams Amithiozone New Drugs for Tuberculosis Major Drugs for the Treatment of Nontuberculous Mycobacterial Infections (see Chapters 253 and 254) Macrolides (see Chapter 29) Antimicrobial Activity and Resistance. Pharmacology. Adverse Reactions. Significant Drug Interactions. Dosage. Rifampin Antimicrobial Activity. Pharmacology, Adverse Events, and Significant Drug Interactions. Usage. Rifabutin Antimicrobial Activity. Pharmacology, Adverse Events, and Significant Drug Interactions. Usage. Aminoglycosides Ethambutol Less Frequently Used Miscellaneous Antimicrobial Agents for Treatment of Nontuberculous Mycobacteria Isoniazid Tetracyclines Sulfonamides Quinolones Linezolid β-Lactams Clofazimine Susceptibility Tests Drugs for Treatment of Leprosy (Hansen’s Disease) Background Dapsone Derivation and Structure. Mechanism of Action. Antimicrobial Activity. Pharmacology. Adverse Reactions. Usage. Availability and Dosage. Rifampin Mechanism of Action and Resistance. Usage. Clofazimine (Lamprene) Derivation and Structure. Mechanism of Action and Antimicrobial Activity. Pharmacology. Adverse Reactions. Usage. Availability and Dosage. Additional or Second-Line Drugs Thiacetazone (Amithiozone) Ethionamide and Protionamide Other Substituted Rifamycins Other Sulfones Acedapsone Sulfoxone Newer Agents Chemotherapy-Associated Reactions in Leprosy Key References References Chapter 39 39 Drugs Active against Fungi, Pneumocystis, and Microsporidia Keywords Short View Summary Amphotericin B–Based Preparations General Features Mechanism of Action Spectrum of Activity and Mechanisms of Resistance Available Formulations Amphotericin B Deoxycholate Formulation. Pharmacology. Nephrotoxicity. Other Chronic Toxicity. Acute Reactions. Administration. Dosage. Lipid-Associated Formulations of Amphotericin B (LFABs) General. Pharmacology and Toxicity. Amphotericin B Colloidal Dispersion. Amphotericin B Lipid Complex. Liposomal Amphotericin B. Comparison of Amphotericin B Deoxycholate and the Lipid-Associated Formulations of Amphotericin B Inhaled Amphotericin B Flucytosine Formulation and Pharmacology. Mechanisms of Action and Resistance. Administration and Dosage. Azole Antifungal Agents General Features Mechanism of Action Itraconazole (Sporanox) Formulations and Pharmacology. Adverse Effects. Interactions. Uses. Fluconazole (Diflucan) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Candidiasis. Cryptococcal Meningitis. Other Mycoses. Prophylaxis in Neutropenic Patients. Prophylaxis in Patients with Acquired Immunodeficiency Syndrome. Prophylaxis in Preterm Neonates. Voriconazole (Vfend) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Aspergillosis. Other Mycoses. Fever and Neutropenia. Posaconazole (Noxafil) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Prophylaxis of Invasive Fungal Infection during Periods of Very High Risk. Oropharyngeal Candidiasis. Therapy of Various Mold Infections. Investigational Triazoles Echinocandin Antifungal Agents General Features Caspofungin (Cancidas) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Candidiasis. Aspergillosis. Empirical Therapy of Presumed Fungal Infections in Febrile, Neutropenic Patients. Mucormycosis. Anidulafungin (Eraxis) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Candidiasis. Use in Other Settings. Micafungin (Mycamine) Formulations and Pharmacology. Drug Interactions. Side Effects. Indications Candidiasis. Prophylaxis of Candidal Infections in Hematopoietic Stem Cell Transplant Recipients. Use in Other Settings. Combination Antifungals Agents Used to Treat and Prevent Pneumocystis Jirovecii Trimethoprim-Sulfamethoxazole Pentamidine Formulations, Pharmacology, and Indications. Drug Interactions. Side Effects. Other Therapies for P. jirovecii Infection Agents Used to Treat Microsporidia Fumagillin Investigational Antifungal Agents Key References References Chapter 40 40 Antimalarial Drugs Keywords Short View Summary Artemisinin Derivatives Structures of Artemisinin Compounds Pharmacokinetics and Dynamics. Clinical Use. Severe Malaria. Resistance. Toxicity. 4-Aminoquinolines Chloroquine Pharmacokinetics. Clinical Use. Resistance. Toxicity. Amodiaquine Pharmacokinetics. Clinical Use. Toxicity. Mefloquine Pharmacokinetics. Clinical Use. Resistance. Toxicity. Quinine and Quinidine Pharmacokinetics. Clinical Use. Quinine Resistance. Quinine for Treatment of Babesiosis. Toxicity. Piperaquine Pharmacokinetics. Clinical Use. Resistance. Toxicity. Pyronaridine Pharmacokinetics. Clinical Use. Toxicity. Halofantrine Pharmacokinetics. Clinical Use. Toxicity. Lumefantrine Pharmacokinetics. Clinical Use. Toxicity. 8-Aminoquinolines Primaquine Pharmacokinetics. Clinical Use. Radical Cure. Prophylaxis. Reduction of Transmission. Toxicity. Tafenoquine Pharmacokinetics. Clinical Use. Toxicity. Atovaquone Pharmacokinetics. Clinical Use. Resistance. Toxicity. Folate Antagonists Dihydrofolate Reductase Inhibitors Proguanil (Chloroguanide) Pharmacokinetics. Pyrimethamine Pharmacokinetics. Toxicity. Trimethoprim Dihydropteroate Synthetase Inhibitors Sulfonamides Sulfadiazine and Sulfamethoxazole Sulfadoxine Pharmacokinetics. Toxicity. Sulfones Antibiotics with Antimalarial Activity Doxycycline and Tetracycline Macrolides Azithromycin Clindamycin Key References References Chapter 41 41 Drugs for Protozoal Infections Other Than Malaria Keywords Short View Summary Drugs for Leishmaniasis and Trypanosomiasis Amphotericin B Antimonials Triazoles Miltefosine (Hexadecylphosphocholine, HePC) Paromomycin Pentamidine Isethionate Benznidazole Eflornithine Melarsoprol Nifurtimox Suramin Nitazoxanide Diloxanide The Nitroimidazoles Spiramycin Atovaquone Other Drugs Rarely Used to Treat Intestinal Protozoal Infections Key References References Chapter 42 42 Drugs for Helminths Keywords Short View Summary Benzimidazoles Albendazole Mebendazole Thiabendazole Triclabendazole Ivermectin Diethylcarbamazine Piperazine Doxycycline Pyrantel Pamoate Levamisole Praziquantel Oxamniquine Metrifonate Niclosamide Bithionol Key References References Chapter 43 43 Antiviral Agents: Keywords Activity of Antiviral Agents Mechanisms of Action Inhibition of Viral Nucleic Acid Synthesis RNA Antisense Nucleotides Viral Entry Inhibition Protease Inhibition Integrase Inhibition Inhibition of Uncoating of Virus Inhibition of Virus Release Host Defense Modifiers Interferons Innate Immunity Stimulators Sialidase Inhibitors Resistance to Antiviral Agents Combinations of Antiviral Agents Virus Load Assays Pharmacodynamics References Chapter 44 44 Antiviral Drugs for Influenza and Other Respiratory Virus Infections Keywords Short View Summary Amantadine and Rimantadine Spectrum Mechanism of Action Resistance Pharmacokinetics Amantadine Rimantadine Interactions Toxicity Clinical Studies Influenza A Other Viruses DAS181 (Fludase) Laninamivir Octanoate Spectrum Mechanism of Action Resistance Pharmacokinetics Toxicity Clinical Studies Oseltamivir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Peramivir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Ribavirin Spectrum Mechanism of Action Resistance Pharmacokinetics Toxicity Interactions Clinical Studies Respiratory Syncytial Virus Other Respiratory Viruses RSV604 Zanamivir Spectrum Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Polymeric Zanamivir Conjugates Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions and Toxicity Clinical Studies Key References References Chapter 45 45 Antivirals against Herpes Viruses Keywords Acyclovir and Valacyclovir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Herpes Simplex Virus Varicella-Zoster Virus Infections Cytomegalovirus Other Viruses Brivudin Cidofovir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies CMX001 Docosanol Famciclovir and Penciclovir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Fomivirsen Foscarnet Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Ganciclovir and Valganciclovir Spectrum Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Idoxuridine Letermovir (AIC246) Trifluridine Vidarabine Maribavir Helicase-Primase Inhibitors (Amenamevir, Pritelivir) Amenamevir (ASP2151) Pritelivir (AIC316) Key References References Chapter 46 46 Antiviral Drugs against Hepatitis Viruses Keywords Short View Summary Hepatitis B Overview Adefovir Spectrum Mechanism of Action Resistance Pharmacology Interactions Toxicity Clinical Studies Entecavir Spectrum and Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Interferons Lamivudine Resistance Toxicity Clinical Studies Telbivudine Spectrum and Mechanism of Action Resistance Pharmacokinetics Interactions Toxicity Clinical Studies Tenofovir Spectrum and Mechanism of Action Resistance Pharmacokinetics Toxicity Clinical Studies in Hepatitis B Virus Infection Other Agents of Potential Interest Emtricitabine Clevudine The Future Hepatitis C Overview Interferons Ribavirin Boceprevir Spectrum Mechanism of Action Resistance Pharmacology Interactions Toxicity Clinical Studies Telaprevir Spectrum Mechanism of Action Resistance Pharmacology Interactions Toxicity Clinical Studies Simeprevir Spectrum Mechanism of Action Resistance Pharmacology Interactions Toxicity Clinical Studies Sofosbuvir Spectrum Mechanism of Action Resistance Pharmacology Interactions Toxicity Clinical Studies Future Therapies Key References References Chapter 47 47 Miscellaneous Antiviral Agents (Interferons, Imiquimod, Pleconaril) Keywords Short View Summary Interferons Classification Mechanisms of Action Pharmacokinetics Interactions Toxicity Clinical Studies Herpesviruses Human Immunodeficiency Virus Papillomavirus Respiratory Viruses Imiquimod and Resiquimod Pleconaril Key References References Chapter 48 48 Immunomodulators Keywords Colony-Stimulating Factors Granulocyte Colony-Stimulating Factor Adverse Effects Granulocyte-Macrophage Colony-Stimulating Factor Adverse Effects Macrophage Colony-Stimulating Factor Interferons Interferon-α Interferon-γ Interleukins Interleukin-1 Interleukin-2 Interleukin-7 Interleukin-10 Interleukin-12 Immunoglobulins and Monoclonal Antibodies Glucocorticosteroids Anti-Inflammatory Strategies for the Treatment of Sepsis Other Immunomodulatory Agents Infection Risk Associated with Anticytokine Therapy Key References References Chapter 49 49 Hyperbaric Oxygen Keywords Short View Summary Physiologic Effects in Animal Models Modulation of Inflammation and Immune Function Angiogenesis and Improved Wound Healing Antibacterial Properties Increased Activity of Antimicrobial Agents Administration Indications Diabetic Foot Ulcerations Necrotizing Soft Tissue Infections Clostridial Myonecrosis (Gas Gangrene) Refractory Osteomyelitis Bacterial Intracranial Abscess Mucormycosis Side Effects and Complications Cost Controversy Certification in Hyperbaric Medicine Conclusions Key References References Chapter 50 50 Complementary and Alternative Medicines for Infectious Diseases Keywords Specific Alternative Agents Artemisinins to Treat Malaria Cranberry to Prevent Urinary Tract Infection Vitamin A for Pneumonia Zinc for Diarrhea in Children of the Developing World Treatment of the Common Cold Zinc Echinacea Milk Thistle for Chronic Hepatitis Green Tea Extract for Warts Caused by Human Papillomavirus Probiotics for Gastrointestinal Diseases Summary Key References References Chapter 51 51 Antimicrobial Stewardship Keywords Antimicrobial Stewardship Philosophy of Antimicrobial Use Antimicrobial Stewardship Strategies Educational Strategies Antimicrobial Formulary Restriction Strategies Prior-Approval and Justification Strategies Prospective Audit and Feedback Strategies Computer-Assisted Stewardship Programs Multidisciplinary and Multistrategy Approaches Outcomes of Antimicrobial Stewardship Programs Clinical Outcomes Economic Outcomes Do Antimicrobial Stewardship Programs Alter Resistance in the Hospital? Design and Implementation The Future Acknowledgment Key References References Chapter 52 52 Designing and Interpreting Clinical Studies in Infectious Diseases Keywords History Defining Terms Choosing a Research Question and Defining Goals of a Study Types of Analytical Study Designs Comparison with a control group Types of Hypotheses Design of Noninferiority Trials Selection of Study Participants Minimizing error in studies Baseline Comparability Between Study Groups Outcome Assessments Analysis of Study Results Analysis of Populations Calculating Differences between Groups Examining the Evidence: P Values and Confidence Intervals Measurement of Harms Subgroup Analyses Examining the Conclusions Key References References Chapter 53 53 Outpatient Parenteral Antimicrobial Therapy Keywords Short View Summary Decision Making in Choosing Patients for OPAT Evidence-Based Data for OPAT Antimicrobial Considerations in OPAT The Infectious Diseases Physician Role and OPAT The Future of OPAT Acknowledgment References Chapter 54 54 Tables of Anti-infective Agent Pharmacology Keywords Dosing Guidelines Dosage Adjustment for Renal Impairment Dosage Adjustment for Hepatic Impairment Dosage Adjustment for Body Size (Obese and Underweight) Drug-Drug Interactions Acknowledgment Suggested Readings Chapter 55 55 Temperature Regulation and the Pathogenesis of Fever Keywords Terminology Clinical Thermometry Anatomic Variability Physiologic Variables “Normal Body Temperature” Thermoregulation The Generation of Fever Acute-Phase Response Endogenous Antipyretics Risk-Benefit Considerations Antipyretic Therapy Diagnostic Considerations Benefits versus Risks Indications Pharmacologic Agents Physical Methods of Antipyresis Key References References Chapter 56 56 Fever of Unknown Origin Keywords Short View Summary Terminology and Definitions Classic Fever of Unknown Origin Infants and Children Elderly Persons Returned Travelers Nosocomial (Health Care–Associated) Fever of Unknown Origin Postoperative Patients Intensive Care Unit Patients Stroke Patients Neutropenic (Immune-Deficient) Fever of Unknown Origin Human Immunodeficiency Virus–Related Fever of Unknown Origin Diagnosis History Verification of Fever and Fever Pattern Physical Examination Laboratory Investigations Imaging Studies Invasive Diagnostic Procedures Therapy Therapeutic Trials Management Prognosis Key References References Chapter 57 57 The Acutely Ill Patient with Fever and Rash Keywords Short View Summary Approach to the Patient Pathogenesis of Rash Differential Diagnosis in Rash Characteristics of the Lesion Maculopapular Rash Nodular Lesions Diffuse Erythema Vesiculobullous Eruptions Petechial and Purpuric Eruptions Enanthems Sweet’s Syndrome Pathogens or Infectious Conditions Strongly Associated with Rash Sepsis Infections due to Neisseria Species Neisseria meningitidis Infection Neisseria gonorrhoeae Infection Pseudomonas Infection Bacterial Endocarditis Infections due to Staphylococcus aureus and Streptococcus pyogenes Staphylococcal Scalded Skin Syndrome Staphylococcal Toxic Shock Syndrome Streptococcal Infections Rickettsial Infections Capnocytophaga canimorsus Infection Borrelia burgdorferi Infection Candidiasis New and Emerging Infectious Diseases Infections due to New Herpesviruses Viral Hemorrhagic Fever Bacterial Diseases due to Bartonella Species Tick-borne Bacterial Diseases due to Ehrlichia and Anaplasma Species Orthopoxviruses Skin Lesions in Immunocompromised Patients Key References References Chapter 58 58 The Common Cold Keywords Short View Summary Etiology Epidemiology Seasonal Incidence Attack Rate Transmission Immunity and Factors Predisposing to Infection or Illness Pathogenesis Clinical Manifestations Differential Diagnosis Laboratory Findings Complications of the Common Cold Therapy Symptomatic Therapies Nasal Congestion Rhinorrhea Sneezing Sore Throat Cough Other Remedies Prevention Key References References Chapter 59 59 Pharyngitis Keywords Short View Summary Etiology Epidemiology Pathogenesis Clinical Manifestations Group A Streptococcus Non–group A Streptococcus Fusobacterium necrophorum Arcanobacterium haemolyticum Corynebacterium diphtheriae Neisseria gonorrhoeae Atypical Bacteria Epstein-Barr Virus Human Immunodeficiency Virus Enteroviruses Adenovirus Herpes Simplex Virus Diagnosis THERAPY Complications Key References References Chapter 60 60 Acute Laryngitis Keywords Short View Summary Key References References Chapter 61 61 Croup in Children (Acute Laryngotracheobronchitis) Keywords Short View Summary History Nomenclature Incidence Etiology Epidemiology Pathophysiology Clinical Manifestations Diagnosis Radiographic Findings Differential Diagnosis Therapy Outcome Acknowledgment Key References References Chapter 62 62 Otitis Externa, Otitis Media, and Mastoiditis Keywords Short View Summary Otitis Externa Pathogenesis Clinical Manifestations and Management Otitis Media Epidemiology Pathogenesis Microbiology Bacteria Viruses Mycoplasma, Chlamydia, and Unusual Organisms Immunology Diagnosis and Clinical Course Management Acute Otitis Media Antimicrobial Agents Treatment of Otalgia Decongestants, Antihistamines, and Corticosteroids Prevention of Acute Otitis Media Chemoprophylaxis Pneumococcal Vaccines Respiratory Virus Vaccines Surgical Management Mastoiditis Pathogenesis Clinical Manifestations Diagnosis Management Key References References Chapter 63 63 Sinusitis Keywords Short View Summary Anatomy and Physiology of the Paranasal Sinuses Pathogenesis Microbiology Chronic Sinusitis Epidemiology Clinical Manifestations Diagnosis Clinical Diagnosis Imaging Therapy Antimicrobial Adjunctive Treatment Corticosteroids Antihistamines/Decongestants Saline Sinus Surgery Complications Prevention Key References References Chapter 64 64 Epiglottitis Keywords Short View Summary Epidemiology and Etiology Clinical Manifestations Diagnosis Differential Diagnosis Therapy Initial Management Antibiotic Therapy Prevention Key References References Chapter 65 65 Infections of the Oral Cavity, Neck, and Head Keywords Short View Summary Microbiologic Considerations Unique Niches of the Indigenous Oral Flora Microbial Specificity in Odontogenic Infections Pathogenetic Mechanisms Mucosal Immunity of the Oral Cavity Anatomic Considerations Clinical Manifestations and Management Orofacial Odontogenic Infections Dentoalveolar Infections Gingivitis and Periodontal Infections Gingivitis Periodontitis Periodontal Abscess Pericoronitis Deep Fascial Space Infections Space Infections around the Face Masticator Spaces. Buccal, Canine, and Parotid Spaces. Suprahyoid Space Infections Submandibular and Sublingual Spaces. Ludwig’s Angina. Lateral Pharyngeal Space. Infrahyoid Space Infections Retropharygeal and Danger Spaces. Pretracheal Space. Complications of Odontogenic Infections Suppurative Jugular Thrombophlebitis (Lemierre Syndrome) and Carotid Artery Erosion Septic Cavernous Sinus Thrombosis Maxillary Sinusitis Osteomyelitis of the Jaws Association with Cardiovascular Risk Orofacial Nonodontogenic Infections Infections of the Oral Mucosa Noma (Gangrenous Stomatitis) Aphthous Stomatitis Mucositis and Stomatitis in the Severely Immunocompromised Patient Infections of the Salivary Gland Suppurative Parotitis Chronic Bacterial Parotitis Viral Parotitis Miscellaneous Infections of the Neck and Head Suppurative Cervical Adenitis Infected Embryologic Cysts Suppurative Thyroiditis Infections from Bites, Irradiation, and Surgical Wounds Human and Animal Bites Irradiation and Postsurgical Wounds Diagnostic Approaches Microbiologic Investigation Imaging Techniques for the Localization of Infection Therapeutic Considerations Dental Caries and Periodontitis Suppurative Soft Tissue Infections Osteomyelitis Key References References Chapter 66 66 Acute Bronchitis Keywords Short View Summary Microbial etiology Pathogenesis Clinical Manifestations Diagnosis Therapy Prevention Key References References Chapter 67 67 Acute Exacerbations of Chronic Obstructive Pulmonary Disease Keywords Short View Summary Epidemiology Clinical Manifestations Diagnosis Acute Exacerbations of COPD Radiology Pathophysiology Mucosal Inflammation Microbes in Stable COPD Microbes in Acute Exacerbations of COPD Nonantimicrobial Therapy for Steady-State COPD Nonantimicrobial Therapy for Acute Exacerbations of COPD Antibiotic Therapy for Acute Exacerbations of COPD Rationale for Antibiotics Whom to Treat Choice of Antibiotic Duration of Antibiotic Therapy Therapy for Viral Infection Prevention of Acute Exacerbations of COPD Antibiotic Prophylaxis in Steady-State COPD Vaccination Key References References Chapter 68 68 Bronchiolitis Keywords Short View Summary Etiology Epidemiology Pathophysiology Clinical Manifestations Complications Diagnosis Therapy Prevention Key References References Chapter 69 69 Acute Pneumonia Keywords Short View Summary Host Defenses and Pathogenesis Pulmonary Defense Systems Impairment of Pulmonary Defenses Clinical Evaluation History Physical Examination Diagnostic Testing Sputum Examination and Examination of Other Respiratory Tract Samples Fiberoptic Bronchoscopy Other Techniques Lung Biopsy Examination of Pleural Effusions Blood Culture, Serologic Studies, and Urine Studies, Including Antigen Detection Radiologic Examination Pneumonia Syndromes Acute Community-Acquired Pneumonia Community-Acquired Pneumonia in the Older Adult Nursing Home Pneumonia Severe Community-Acquired Pneumonia Health Care–Associated Pneumonia Atypical Pneumonia Syndrome Pneumonia in the Setting of Aspiration Eosinophilic Pneumonias Hospital-Acquired Pneumonia Pneumonia in the Immunosuppressed Host Therapy Antimicrobial Therapy Timing of Antibiotics Duration of Treatment and Use of Clinical Practice Guidelines Adjunctive Therapy Prevention Key References References Chapter 70 70 Pleural Effusion and Empyema Keywords Short View Summary Pathophysiology Microbiology Clinical Manifestations Imaging Studies Laboratory Diagnosis Treatment Antimicrobial Therapy Drainage Fibrinolytic Therapy Empyema Complicating Bronchopleural Fistula Surgical Intervention for Drainage Key References References Chapter 71 71 Bacterial Lung Abscess Keywords Short View Summary Classification Pathophysiology Microbiology Clinical Manifestations Diagnosis Differential Diagnosis Therapy Antimicrobial Therapy Duration of Therapy Bronchoscopy Surgical Intervention Response to Therapy Prognosis References Chapter 72 72 Chronic Pneumonia Keywords Short View Summary Causes Epidemiology Age, Gender, and Race Occupation and Hobbies Residence and Travel Contacts, Habits, and Drugs Underlying Disease Clinical Features Symptoms Signs Diagnostic Procedures Initial Laboratory Studies Additional Studies Chest Radiographic Studies Patients with Radiographic Evidence of Localized Infiltrates or Cavitation Invasive Procedures Patients with Radiographic Evidence of Diffuse Pulmonary Infiltration and Fibrosis Therapy Antimicrobial Agents Corticosteroids Bronchoscopy and Surgery Key References References Chapter 73 73 Cystic Fibrosis Keywords Short View Summary Clinical Disease: Acute Pulmonary Exacerbations Pathogenesis of Cystic Fibrosis–Related Lung Disease Cystic Fibrosis Microbiome Major Cystic Fibrosis Pathogens Staphylococcus aureus Methicillin-Resistant Staphylococcus aureus Pseudomonas aeruginosa Burkholderia cepacia Complex Other Bacteria Nontuberculous Mycobacteria Respiratory Viruses Fungal Disease Therapy Antimicrobial Therapy Azithromycin Inhaled Antibiotics Cystic Fibrosis–Specific Antibiotic Treatment Approaches and Dosing Nonantibacterial-Based Treatments CFTR Modulators Infection Control Lung Transplantation Key References References Chapter 74 74 Urinary Tract Infections Keywords Short View Summary Terminology Pathologic Characteristics Acute Pyelonephritis Chronic Pyelonephritis (Chronic Interstitial Nephritis) Papillary Necrosis Caused by Infection Pathogenesis of Urinary Tract Infection Ascending Route Hematogenous Route Lymphatic Route Urovirulence in Bacteria Adhesins Fimbriae P Fimbriae Type I Fimbriae Other Adhesins Expression and Selection of Virulence Factors Other Virulence Factors of Uropathogenic E. coli Host Defense of the Urinary Tract Innate Immunity Urine and Bladder Defenses Adherence and Colonization Humoral and Cellular Immunity Genetic Factors Structural Abnormalities Epidemiology and Natural History of Urinary Tract Infection Infecting Organisms Asymptomatic Bacteriuria versus Symptomatic Infection Urinary Tract Infection in Children Urinary Tract Infection in Adults Urinary Tract Infection in the Elderly Urinary Tract Infection in Other Conditions Clinical Manifestations Symptoms Alterations in Renal Function Diagnosis Presumptive Diagnosis of Urinary Tract Infection Diagnosis of Urinary Tract Infection by Culture General Considerations Urinary Tract Infection with Low Numbers of Organisms Localization of Site of Infection Management of Urinary Tract Infection General Considerations Nonantimicrobial Therapy and Prevention Hydration Urinary pH Analgesics Prevention of Urinary Tract Infection Principles of Antimicrobial Therapy Serum, Tissue, and Urine Concentrations of Antimicrobial Agents Response to Therapy Bacteriologic Cure Bacteriologic Persistence Bacteriologic Relapse Reinfection Considerations in Choice of Therapy Classification and Antimicrobial Therapy for Different Groups Infection in Children Acute Uncomplicated Pyelonephritis in Women Oral Therapy Parenteral Therapy Uncomplicated Cystitis in Women Complicated Urinary Tract Infection Including Infection in Men Asymptomatic Bacteriuria Relapsing Urinary Tract Infection Reinfection of the Urinary Tract and Antimicrobial Prophylaxis Fungal Infections Urinary Tract Infection in Pregnancy Physiologic Alterations in the Urinary Tract Epidemiology Management of Bacteriuria of Pregnancy Perinephric Abscess and Intrarenal Abscess Perinephric Abscess Intrarenal Abscess Diagnosis and Therapy Imaging Studies Surgical Management Summary of Treatment Approaches Key References References Chapter 75 75 Sepsis, Severe Sepsis, and Septic Shock Keywords Short View Summary Introduction and Definitions Epidemiology Pathogenesis Early Host Responses to Infection Local Defenses: Walling Off and Killing Invading Microbes Early Systemic Responses: Keeping Infection and Inflammation Localized Central Nervous System Regulation of Systemic Responses The Liver: Essential Roles in Systemic Responses to Infection Acute Phase Responses Anti-infective Responses Anti-inflammatory Responses Metabolic Responses Procoagulant Responses Thermoregulatory Responses Summary Harmful Responses to Infection: Severe Sepsis and Septic Shock Severe Sepsis Cytokines and Other Mediators Other Candidate Triggers Complement Activation Coagulopathy Activation or Injury of the Vascular Endothelium Mitochondrial and Microcirculatory Dysfunction Immunosuppression Septic Shock Infection Susceptibility and Outcome: Genetic Influences Microbial Triggers for Severe Sepsis Bacteremia Endotoxemia Other Bacterial Toxins Summary Recovery Mechanisms Clinical Manifestations Nervous and Neuroendocrine Systems Cerebral Function Hypothalamic-Pituitary-Adrenal Axis Adrenal Insufficiency Autonomic Dysfunction Peripheral Nerves, Muscles Blood Compartment Blood Cells Plasma Lipids Glucose Lactate Clotting Factors Dysfunction of Other Organs Acute Lung Injury Renal Dysfunction Gastrointestinal Tract Injury Hepatic Dysfunction Immune Dysfunction Cutaneous Manifestations Septic Shock Severe Sepsis and Septic Shock: Is There a “Tipping Point”? Diagnosis Differential Diagnosis Cultures Diagnostic Imaging Cytokine and Biomarker Levels Adrenal Insufficiency in Patients with Septic Shock Therapy Antimicrobial Drugs Antimicrobial Chemotherapy for Specific Etiologies of Severe Sepsis Surgical Drainage (Source Control) Intravenous Fluids and Vasopressors Other Therapies Glucocorticoids Anti-inflammatory Drugs Antagonists to Gram-Negative Bacterial Endotoxin and Related Molecules Anticoagulants Boosting Host Defenses Summary Nutrition and Other Supportive Measures Preventing Secondary Infections Prognosis Key References References Chapter 76 76 Peritonitis and Intraperitoneal Abscesses Keywords Short View Summary Anatomy and Physiology Peritonitis Primary Peritonitis Etiology Bacteriologic Characteristics Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Prognosis Therapy Prevention Secondary and Tertiary Peritonitis Etiology Microbiologic Characteristics Pathogenesis Pathophysiologic Responses Local Response Systemic Response Gastrointestinal. Cardiovascular. Respiratory. Renal. Metabolic. Clinical Manifestations Symptoms Physical Findings Diagnostic Studies Prognosis Therapy Antimicrobial Therapy Chloramphenicol. Clindamycin. Metronidazole. Tetracyclines. Cephalosporins. Penicillins. Other β-Lactams. Aminoglycosides. Fluoroquinolones. Tigecycline. Pharmacodynamic Considerations Duration of Antimicrobial Therapy. Hyperbaric Oxygen Gastrointestinal Drainage Water and Electrolyte Administration Blood and Plasma Transfusion Respiratory Support Operative Approach Prevention Peritonitis during Peritoneal Dialysis Long-Term Peritoneal Dialysis Acute Peritoneal Dialysis Intraperitoneal Abscesses Etiology Bacteriologic Findings Pathogenesis Clinical Manifestations Diagnosis Prognosis Therapy Key References References Chapter 77 77 Infections of the Liver and Biliary System (Liver Abscess, Cholangitis, Cholecystitis) Keywords Short View Summary Liver Abscess Epidemiology/Etiology Amebic Liver Abscess Pyogenic Liver Abscess Pathogenesis and Pathophysiology Amebic Liver Abscess Pyogenic Liver Abscess Microbiology Amebic Liver Abscess Pyogenic Liver Abscess Epidemic Klebsiella pneumoniae Pyogenic Liver Abscess Clinical Manifestations Amebic Liver Abscess Pyogenic Liver Abscess Diagnosis Therapy Amebic Liver Abscess Pyogenic Liver Abscess Infection of the Biliary System Pathogenesis Cholecystitis Acalculous Cholecystitis Cholangitis Clinical Manifestations Diagnosis Imaging Studies Microbiology AIDS Cholangiopathy (AIDS-Related Sclerosing Cholangitis) Therapy Acute Cholangitis Key References References Chapter 78 78 Pancreatic Infection Keywords Short View Summary Infectious Causes of Acute Pancreatitis Pancreatitis and Human Immunodeficiency Virus Infection Infection Complicating Acute Pancreatitis Background Significance of Infection in Acute Pancreatitis Defining Pancreatic Infections Diagnosis of Pancreatic Infection Microbiology of Pancreatic Infection Management of Pancreatic Infection Prevention of Pancreatic Infection Early Enteral Feeding Selective Gut Decontamination Preemptive Systemic Antibiotic Therapy Additional Data Review Article Recommendations Guidelines General Practice Conclusions Key References References Chapter 79 79 Splenic Abscess Keywords Short View Summary Epidemiology Pathogenesis Microbiology Clinical Manifestations Diagnosis Ultrasonography Computed Tomography Magnetic Resonance Imaging Therapy References Chapter 80 80 Appendicitis Keywords Short View Summary Epidemiology Pathogenesis Microbiology Clinical Manifestations Diagnosis Therapy Key References References Chapter 81 81 Diverticulitis and Typhlitis Keywords Short View Summary Diverticulitis Epidemiology Pathogenesis Microbiology Clinical Manifestations Diagnosis Therapy Typhlitis (Neutropenic Enterocolitis) Pathogenesis Clinical Manifestations Diagnosis Therapy Key References References Chapter 82 82 Endocarditis and Intravascular Infections Keywords Short View Summary Infective Endocarditis Epidemiology Pathogenesis and Pathophysiology Nonbacterial Thrombotic Endocarditis Hemodynamic Factors Transient Bacteremia Microorganism–Nonbacterial Thrombotic Endocarditis Interaction Immunopathologic Factors Pathologic Changes Heart Kidney Mycotic Aneurysms Central Nervous System Spleen Lung Skin Eye Clinical Manifestations Infective Endocarditis in Drug Addicts Laboratory Findings Special Diagnostic Tests Etiologic Agents Streptococci Staphylococci Gram-Negative Bacilli Unusual Gram-Negative Bacteria Gram-Positive Bacilli Anaerobic Bacteria Other Bacteria Etiology of Infective Endocarditis in Injection Drug Users Fungi Other Bacteria Viruses Culture-Negative Endocarditis Polymicrobial Endocarditis Therapy for Infective Endocarditis Tests Useful for Antimicrobial Treatment Monitoring Antimicrobial Therapy Penicillin-Sensitive Streptococcal Endocarditis Endocarditis Caused by Streptococci with Penicillin MIC Greater Than 0.5 µg/mL or by Enterococci Alternatives to Full-Course Aminoglycoside Therapy for Enterococcal Infective Endocarditis Staphylococcal Endocarditis Endocarditis Due to Enterobacteriaceae or Pseudomonas Species Endocarditis Due to Anaerobic Bacilli Pneumococcal, Gonococcal, and Meningococcal Endocarditis Fungal Endocarditis Q Fever Endocarditis Infective Endocarditis Due to Chlamydiae Culture-Negative Endocarditis Surgical Therapy Suppurative Thrombophlebitis Epidemiology Pathogenesis Pathologic Changes Clinical Manifestations Laboratory Findings Etiologic Agents Presumptive Therapy Prevention Infective Endarteritis and Mycotic Aneurysms Epidemiology Pathogenesis Pathologic Changes Clinical Manifestations Laboratory Findings Etiologic Agents Therapy Key References References Chapter 83 83 Prosthetic Valve Endocarditis Keywords Short View Summary Epidemiology Microbiology Early- and Late-Onset Prosthetic Valve Endocarditis Health Care–Associated Prosthetic Valve Endocarditis Community-Acquired Prosthetic Valve Endocarditis Pathogenesis Microbial Adherence Formation and Growth of Vegetations Persistence and Growth of Microorganisms Tissue Destruction and Invasion Pathology Clinical Presentation Diagnosis Echocardiography Identification of the Pathogen Blood Cultures Valve Culture Serologic Methods Broad-Range Bacterial rDNA Polymerase Chain Reaction Histology Evaluation of Bloodstream Infection in Patients with a Prosthetic Valve Management Antimicrobial Therapy Staphylococcal Prosthetic Valve Endocarditis Streptococcal Prosthetic Valve Endocarditis Enterococcal Prosthetic Valve Endocarditis HACEK Prosthetic Valve Endocarditis Diphtheroid Prosthetic Valve Endocarditis Enteric Gram-Negative Bacillary Prosthetic Valve Endocarditis Fungal Prosthetic Valve Endocarditis Culture-Negative Prosthetic Valve Endocarditis Indications for Surgical Intervention Severe Heart Failure Due to Prosthetic Valve Dysfunction Perivalvular Extension of Infection Virulent Pathogens Multiple Emboli Timing of Surgery Timing of Surgery in Patients with Central Nervous System Embolism Surgical Treatment Outcome of Patients Treated Surgically for PVE Duration of Antimicrobial Therapy Postoperatively Anticoagulation Therapy Prevention Key References References Chapter 84 84 Infections of Nonvalvular Cardiovascular Devices Keywords Short View Summary Cardiovascular Implantable Electronic Devices Epidemiology Pathogenesis Risk Factors Microbiology Clinical Manifestations Diagnosis Role of Echocardiography Complications Management Prevention Left Ventricular Assist Devices Epidemiology Pathogenesis Risk Factors Clinical Manifestations Microbiology Management Prevention Prosthetic Vascular Grafts Epidemiology Pathogenesis Risk Factors Microbiology Clinical Manifestations Diagnosis Management Prevention Hemodialysis Prosthetic Vascular Grafts Epidemiology Clinical Manifestations Management Prevention Invasive Nonsurgical Cardiologic Procedures Epidemiology Risk Factors Clinical Manifestations Microbiology Treatment Prevention Coronary Artery Stents Peripheral Vascular Stents Epidemiology Diagnosis Management and Outcome Prevention Vascular Closure Devices Epidemiology and Clinical Manifestations Microbiology Management Prevention Intra-Aortic Balloon Pumps Vena Cava Filters Dacron Carotid Patches Clinical Manifestations Management Cardiac Suture Line Infections Clinical Manifestations Management Closure Device Treatment of Patent Ductus Arteriosus, Atrial Septal Defect, and Ventricular Septal Defect Key References References Chapter 85 85 Prophylaxis of Infective Endocarditis Keywords Short View Summary Pathogenesis of Infective Endocarditis in the Context of Prevention Potential Interventions to Prevent Endocarditis Correction of Predisposing Cardiac Conditions Minimization of Portals of Entry for Microorganisms Prevention of Health Care–Associated Infections Immunization against Bacteria That Can Cause Infective Endocarditis Inhibition of Bacterial Adherence to Endocardium Administration of Systemic Antibiotics Estimation of Risk for Infective Endocarditis Procedures Causing Bacteremia Preexisting Cardiac Conditions Indirect Evidence on Efficacy of Prophylaxis Anecdotal Clinical Observations Case-Control Studies In Vitro Antibiotic Susceptibility Studies Experimental Infective Endocarditis Cost-Benefit and Cost-Effectiveness Analyses Evolution of Clinical Practice in Prevention of Infective Endocarditis Early Results of Changed Guidelines for Infective Endocarditis Prevention Specific Issues in Prevention of Infective Endocarditis Cardiac Catheters, Pacemakers, and Intravascular Devices Valvuloplasty and Valve Replacement Prosthetic Heart Valves Cardiac Assist Devices and Artificial Hearts Cardiac Transplantation Medical Diagnostic Procedures Invasive Procedures Involving Infected Sites Timing of Prophylaxis Duration of Prophylaxis Prevention of Rheumatic Fever versus Prevention of Infective Endocarditis Prophylaxis of Infective Endocarditis for Children Anticoagulant Therapy Medicolegal Liability Issues Summary of Current Recommendations Key References References Chapter 86 86 Myocarditis and Pericarditis Keywords Short View Summary Myocarditis Etiologic Agents Nonviral Pathogens That Cause Myocarditis Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Pericarditis Etiologic Agents Pathology, Pathogenesis, and Pathophysiology Clinical Manifestations Diagnosis Treatment Key References References Chapter 87 87 Mediastinitis Keywords Short View Summary Anatomic Considerations Acute Mediastinitis Epidemiology and Pathogenesis Mediastinitis Secondary to Esophageal Perforation Mediastinitis Secondary to Head and Neck Infections or from Other Sites Mediastinitis Secondary to Cardiothoracic Surgery Bacteriology Clinical Manifestations and Diagnosis Therapy Prevention Complications and Prognosis Chronic/Fibrosing Mediastinitis Key References References Chapter 88 88 Approach to the Patient with Central Nervous System Infection Keywords Clinical Manifestations Meningitis Encephalitis Focal Central Nervous System Syndromes Lumbar Puncture Opening Pressure and Appearance Cell Count Glucose and Protein Other Cerebrospinal Fluid Tests Neuroimaging Studies Management Antimicrobial Therapy Surgical Therapy Adjunctive Therapy References Chapter 89 89 Acute Meningitis Keywords Short View Summary Epidemiology and Etiology Viral Meningitis Enteroviruses Mumps Virus Herpesviruses Other Viruses Bacterial Meningitis Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Listeria monocytogenes Streptococcus agalactiae (Group B Streptococcus) Aerobic Gram-Negative Bacilli Staphylococci Other Bacteria Spirochetal Meningitis Treponema pallidum Borrelia burgdorferi Protozoal and Helminthic Meningitis Amebas Angiostrongylus cantonensis Pathogenesis and Pathophysiology Viral Meningitis Initiation of Infection Viremia and Central Nervous System Invasion Virus Spread within the Central Nervous System Bacterial Meningitis Mucosal Colonization and Systemic Invasion Intravascular Survival Meningeal Invasion Bacterial Survival within the Subarachnoid Space Induction of Subarachnoid Space Inflammation Alterations of the Blood-Brain Barrier Increased Intracranial Pressure and Cerebral Edema Alterations in Cerebral Blood Flow Neuronal Injury Clinical Manifestations Viral Meningitis Enteroviruses Mumps Virus Herpesviruses Bacterial Meningitis Neonates, Infants, and Children Adults Older Adults Underlying Conditions Pathogen-Specific Findings Spirochetal Meningitis Treponema pallidum Borrelia burgdorferi Protozoal and Helminthic Meningitis Amebas Angiostrongylus cantonensis Diagnosis Viral Meningitis Cerebrospinal Fluid Examination Bacterial Meningitis Cerebrospinal Fluid Examination Differentiation of Bacterial from Viral Meningitis Radiography Spirochetal Meningitis Treponema pallidum Borrelia burgdorferi Protozoal and Helminthic Meningitis Amebas Angiostrongylus cantonensis Initial Management of Patients with Acute Meningitis Adjunctive Corticosteroids Experimental Data Clinical Studies in Infants and Children Clinical Studies in Adults Antimicrobial Therapy Viral Meningitis Bacterial Meningitis Principles of Therapy Specific Antimicrobial Therapy Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Listeria monocytogenes Streptococcus agalactiae Aerobic Gram-Negative Bacilli Staphylococci Other Bacteria Duration of Therapy Spirochetal Meningitis Treponema pallidum Borrelia burgdorferi Protozoal and Helminthic Meningitis Amebas Angiostrongylus cantonensis Adjunctive Therapy Viral Meningitis Bacterial Meningitis Anti-inflammatory Agents Reduction of Intracranial Pressure Surgery Helminthic Meningitis Prevention Bacterial Meningitis Haemophilus influenzae Chemoprophylaxis Neisseria meningitidis Chemoprophylaxis Streptococcus pneumoniae Chemoprophylaxis Streptococcus agalactiae Chemoprophylaxis Basilar Skull Fracture Haemophilus influenzae Immunoprophylaxis Neisseria meningitidis Immunoprophylaxis Streptococcus pneumoniae Immunoprophylaxis Key References References Chapter 90 90 Chronic Meningitis Keywords Short View Summary Myelitis, Myeloradiculitis, and Polyradiculitis Encephalitis Brain Abscess Chronic Meningitis Clinical Manifestations Diagnosis Physical Examination History Imaging Laboratory Findings Cerebrospinal Fluid Peripheral Blood Brain Biopsy Differential Diagnosis Cryptococcus Meningitis Coccidioides Meningitis Histoplasma Meningitis Candida Meningitis Sporothrix Meningitis Blastomyces Meningitis Phaeohyphomycotic Meningitis Other Molds Causing Meningitis Mycobacterium tuberculosis Meningitis Treponema pallidum Meningitis Borrelia burgdorferi Tropheryma whipplei Meningitis Nocardia and Actinomyces Meningitis Brucella Meningitis Acanthamoeba Granulomatous Meningitis Angiostrongylus cantonensis Meningitis Taenia solium Meningitis Enteroviral Meningitis Postneurosurgical Meningitis Sarcoidosis Meningitis Vogt-Koyanagi-Harada Syndrome Meningitis Behçet’s Syndrome Meningitis Neoplastic Meningitis Empirical Therapy for Presumed Tuberculous Meningitis References Chapter 91 91 Encephalitis Keywords Short View Summary General Clinical Approach Clinical Manifestations Diagnostic Tests Neuroimaging Cerebrospinal Fluid Analysis Cerebrospinal Fluid Profile Polymerase Chain Reaction and Antibody Studies Electroencephalography Other Diagnostic Studies Management Viral Etiologies of Encephalitis Herpesviruses Herpes Simplex Virus Types 1 and 2 Varicella-Zoster Virus Cytomegalovirus Epstein-Barr Virus Human Herpesvirus Type 6 Herpesvirus B Vector-Borne Viral Infections Pathogenesis West Nile Virus St. Louis Encephalitis Eastern Equine Encephalitis Virus Western Equine Encephalitis Venezuelan Equine Encephalitis California Encephalitis Group Japanese Encephalitis Influenza Colorado Tick Fever Virus Enteroviruses Poliovirus Nonpoliovirus Enteroviruses Rabies Virus Measles Virus Key References References Chapter 92 92 Brain Abscess Keywords Short View Summary Epidemiology and Etiology Bacterial Brain Abscess Fungal Brain Abscess Protozoal and Helminthic Brain Abscess Pathogenesis and Pathophysiology Pathogenesis Initiation of Infection Natural History of Infection Host Defense Mechanisms Clinical Presentation Diagnosis Initial Management of the Patient with Brain Abscess Therapy Bacterial Brain Abscess Antimicrobial Therapy Surgical Therapy Fungal Brain Abscess Key References References Chapter 93 93 Subdural Empyema, Epidural Abscess, and Suppurative Intracranial Thrombophlebitis Keywords Short View Summary Subdural Empyema Epidemiology and Etiology Clinical Features Diagnosis Management and Outcome Epidural Abscess Epidemiology and Etiology Clinical Features Diagnosis Management and Outcome Suppurative Intracranial Thrombophlebitis Epidemiology and Etiology Clinical Features Diagnosis Management and Outcome Key References References Chapter 94 94 Cerebrospinal Fluid Shunt and Drain Infections Keywords Short View Summary Epidemiology Etiology Pathogenesis Clinical Features Diagnosis Therapy Antimicrobial Therapy Shunt Removal Duration of Antimicrobial Therapy and Shunt Reimplantation Prevention Antimicrobial Prophylaxis Antimicrobial-Impregnated Catheters Combined Interventions Key References References Chapter 95 95 Cellulitis, Necrotizing Fasciitis, and Subcutaneous Tissue Infections Keywords Short View Summary Cellulitis and Superficial Infections Primary Pyodermas Impetigo Pathologic Characteristics and Pathogenesis. Clinical Manifestations. Laboratory Findings. Etiologic Agents. Differential Diagnosis. Presumptive Therapy. Bullous Impetigo Clinical Manifestations. Presumptive Therapy. Staphylococcal Scalded Skin Syndrome Clinical Manifestations. Presumptive Therapy. Staphylococcal Scarlet Fever Toxic Shock Syndrome Folliculitis Furuncles and Carbuncles Definition and Pathologic Characteristics. Clinical Manifestations. Presumptive Therapy. Ecthyma Clinical Manifestations. Chancriform Lesions: Anthrax Pathogenesis. Clinical Manifestations. Presumptive Therapy. Erysipelas Clinical Manifestations. Differential Diagnosis. Presumptive Therapy. Cellulitis Clinical Manifestations. Presumptive Therapy. Membranous Ulcers Cutaneous Diphtheria Clinical Manifestations. Laboratory Findings. Differential Diagnosis. Presumptive Therapy. Infectious Gangrene (Gangrenous Cellulitis) Pathologic Characteristics and Pathogenesis. Clinical Manifestations Streptococcal Gangrene. Progressive Bacterial Synergistic Gangrene. Gas Gangrene, Anaerobic Cellulitis, and Other Forms of Crepitant Cellulitis. Gangrenous Cellulitis in Immunocompromised Hosts. Differential Diagnosis. Presumptive Therapy. Erythrasma Clinical Manifestations. Secondary Bacterial Infections Complicating Preexisting Skin Lesions Diabetic Foot and Other Chronic Superficial Skin Ulcers Decubitus Ulcers Diabetic Ulcers Occupation-Related Ulcers Post-traumatic Opportunistic Skin Infections in Immunocompromised Patients Bacillary Angiomatosis in Patients with Acquired Immunodeficiency Syndrome Hidradenitis Suppurativa Infected Epidermal Cysts Self-Induced Skin Infections Cutaneous Involvement in Systemic Bacterial and Mycotic Infections Bacteremias Staphylococcus aureus Pseudomonas aeruginosa Neisseria meningitidis Neisseria gonorrhoeae Salmonella enterica serotype Typhi Haemophilus influenzae Helicobacter cinaedi Infective Endocarditis Fungemias: Candida albicans Subcutaneous Tissue Infections and Abscesses Clostridial Anaerobic Cellulitis Pathologic Characteristics and Pathogenesis. Clinical Manifestations. Etiologic Agents. Differential Diagnosis. Presumptive Therapy. Nonclostridial Anaerobic Cellulitis Necrotizing Fasciitis Clinical Manifestations. Fournier’s Gangrene. Other Special Anatomic Forms of Necrotizing Fasciitis. Other Microbial Causes of Necrotizing Fasciitis. Differential Diagnosis. Presumptive Therapy. Synergistic Necrotizing Cellulitis Clinical Manifestations. Etiologic Agents. Presumptive Therapy. Miscellaneous Infections Secondary to Trauma Bite Infections Burn Infections Injection Site Abscesses Factitial Disease (Self-Induced Abscesses) Subcutaneous Infections Originating in Contiguous Foci Osteomyelitis Actinomycosis Primary Pyodermas Subcutaneous Abscesses in the Course of Bacteremic Infections Mycetoma Key References References Chapter 96 96 Myositis and Myonecrosis Keywords Short View Summary Pyomyositis Pathogenesis and Pathologic Characteristics Clinical Manifestations Etiologic Agents Differential Diagnosis Diagnosis Empirical Therapy Group a Streptococcal Necrotizing Myositis Gas Gangrene (Clostridial Myonecrosis) Pathogenesis and Pathologic Characteristics Clinical Manifestations Laboratory Findings Etiologic Agents Differential Diagnosis Empirical Therapy Nonclostridial (Crepitant) Myositis Anaerobic Streptococcal Myonecrosis Synergistic Nonclostridial Anaerobic Myonecrosis Infected Vascular Gangrene Aeromonas hydrophila Myonecrosis Psoas Abscess Other Specific Sites of Muscle Abscesses Myalgias Influenza Infective Endocarditis Toxoplasmosis Other Causes Pleurodynia Syndromes Myalgias with Eosinophilia (Parasitic Myositis) Trichinosis Cysticercosis (Cysticercus cellulosae Myositis) Muscle Degeneration Associated with Infections at Other Sites Acute Rhabdomyolysis Muscle Proteolysis and Mediators of Fever in Patients with Sepsis Key References References Chapter 97 97 Lymphadenitis and Lymphangitis Keywords Short View Summary Lymphadenitis Pathogenesis and Pathologic Changes Acute Lymphadenitis Chronic Lymphadenitis Clinical Manifestations Acute Regional Lymphadenitis Due to Pyogenic Bacteria Syndromes Due to Suppurative Lymphadenitis at Specific Anatomic Sites Cervical Lymphadenitis Acute Axillary Lymphadenitis Subpectoral Lymphadenitis Deep Neck Space Lymphadenitis Acute Mediastinal Lymphadenitis Acute Suppurative Epitrochlear Lymphadenitis Suppurative Iliac Lymphadenitis Acute Regional Lymphadenitis Due to Infecting Agents Other Than Pyogenic Bacteria Specific Types of Nonpyogenic Regional Lymphadenitis Scrofula (Tuberculous Cervical Lymphadenitis) Granulomatous Lymphadenitis Caused by Nondiphtheria Corynebacteria Oculoglandular (Parinaud’s) Syndrome Cat-Scratch Disease Mediastinal Lymphadenopathy Inguinal Buboes of Sexually Transmitted Disease Inguinal Buboes of Other Than Sexually Transmitted Disease Origin Generalized Lymphadenitis Associated with Systemic Infections Recurrent Lymphadenitis Periodic Fever, Aphthous Ulcers, Pharyngitis, and Adenitis Syndrome Filarial Lymphangitis Etiologic Agents and Differential Diagnosis Generalized Lymphadenopathy with Acquired Immunodeficiency Syndrome Presumptive Treatment of Lymphadenitis Lymphangitis Pathologic Changes and Pathogenesis Clinical Findings Acute Lymphangitis Chronic Granulomatous Lymphangitis Pseudolymphangitis Etiologic Agents Differential Diagnosis Presumptive Therapy Key References References Chapter 98 98 Syndromes of Enteric Infection Keywords Occurrence and Scope of Gastrointestinal Infections in Developing Countries Occurrence and Scope of Gastrointestinal Infections in Developed Countries Pathogens Associated with Gastrointestinal Infections Behavioral and Environmental Factors in Gastrointestinal Infection Host Factors in Gastrointestinal Infection Age Gastric Acidity and Physical Barriers Intestinal Microbiome Immunocompromise Genetic Determinants Nutritional Status Microbial Factors in Gastrointestinal Infection Inoculum Size Adherence/Attachment Invasion Toxins Neurotoxins Enterotoxins Cytotoxins Major Clinical Syndromes Acute Vomiting Acute Watery Diarrhea Invasive Diarrhea Persistent Diarrhea Enteric Fever Complications of Acute Enteric Infection Asymptomatic Passage of Enteropathogens Diagnostic Approach to Enteric Infections Therapy for Enteric Infections Prevention and Control of Enteric Infections Key References References Chapter 99 99 Esophagitis Keywords Short View Summary Clinical Manifestations Specific Etiologic Agents Candida Esophagitis Cytomegalovirus Esophagitis Herpes Simplex Virus Esophagitis Aphthous (Idiopathic) Ulceration of the Esophagus Management of Esophageal Infection General Considerations in Therapy Esophagitis in Patients with Acquired Immunodeficiency Syndrome Key References References Chapter 100 100 Nausea, Vomiting, and Noninflammatory Diarrhea Keywords Short View Summary Epidemic Diarrhea in Newborn Nurseries Weanling Diarrhea Diarrhea Caused by Rotavirus Acute Nausea and Vomiting (Winter Vomiting Disease) Acute Noninflammatory Diarrhea in Adults Treatment of Acute Noninflammatory Diarrhea Diarrhea in HIV-Infected Patients Diarrhea in Institutions Hospitals Long-term Care Facilities Daycare Centers Traveler’s Diarrhea (Turista) Differential Diagnosis of Acute Noninflammatory Diarrhea Chronic Noninflammatory Diarrhea Bacterial Overgrowth Syndromes Other Bacterial Overgrowth Syndromes Key References References Chapter 101 101 Bacterial Inflammatory Enteritides Keywords Short View Summary Definition Epidemiology Microbiology Shigella spp. and Enteroinvasive Escherichia coli Enterohemorrhagic Escherichia coli Diarrhea Campylobacter Enteritis Clostridium difficile Colitis Vibriosis Salmonellosis and Typhoid Fever Yersiniosis Gonococcal Proctitis Unusual Causes of Dysentery Diagnosis, Therapy, and Prevention Necrotizing Enterocolitis in the Newborn Darmbrand, Pig-Bel, Necrotizing Enteritis in Adults (Enteritis Necroticans) Chronic Inflammatory Processes Enteropathogenic and Enteroaggregative Escherichia coli Syphilis Gastrointestinal Tuberculosis Key References References Chapter 102 102 Enteric Fever and Other Causes of Fever and Abdominal Symptoms Keywords Short View Summary Enteric Fever (Typhoid and Paratyphoid Fever) History Etiologic Agents of Enteric Fever Nomenclature and Classification of Typhoidal Salmonella enterica Clinical Distinction between Typhoidal and Nontyphoidal Salmonella enterica Genomic Features Epidemiology Burden and Distribution Severity Source of Infection Mode of Transmission Acquisition of Disease in Areas Where Enteric Fever Occurs Sporadically Antibiotic Resistance and Emergence of Pandemic S. Typhi Host Factors and Susceptibility to Infection Pathogenesis Overview Invasion Latency and Dissemination Intestinal and Other Local Pathology Relapse and Chronic Carriage Clinical Manifestations Uncomplicated Typhoid Fever Laboratory Findings in Uncomplicated Infection Severe Illness Gastrointestinal Complications Neurologic Complications Metastatic Pyogenic Complication Diagnosis Culture-Based Diagnostics Serologic Management Chloramphenicol, Ampicillin, and Trimethoprim-Sulfamethoxazole Fluoroquinolones Cephalosporins Azithromycin Adjunctive Therapy Supportive Care and Management of Complications Treatment of Relapse and Chronic Carriage Prevention Differential Diagnosis of Enteric and Typhoidal Fevers Bacteremia Associated with Nontyphoidal Salmonella Typhoidal Fever Additional Causes of Prolonged or Persistent Fever Assessing an Individual with an Acute Febrile Illness in a Resource-Limited Area or after International Travel Fever and Mesenteric Adenitis or Ileocecitis Fever, Abdominal Pain, and Peripheral Eosinophilia Key References References Chapter 103 103 Foodborne Disease Keywords Short View Summary Pathogenesis and Clinical Manifestations Foodborne Syndromes Caused by Microbial Agents or Their Toxins Nausea and Vomiting within 1 to 8 Hours. Abdominal Cramps and Diarrhea within 8 to 16 Hours. Fever, Abdominal Cramps, and Diarrhea within 6 to 48 Hours. Abdominal Cramps and Watery Diarrhea within 16 to 72 Hours. Vomiting and Nonbloody Diarrhea within 10 to 51 Hours. Fever and Abdominal Cramps within 1 to 11 Days, with or without Diarrhea. Bloody Diarrhea with Minimal Fever within 3 to 8 Days. Paralysis within 18 to 36 Hours. Persistent Diarrhea within 1 to 3 Weeks. Systemic Illness. Postinfection Syndromes. Foodborne Syndromes Caused by Nonbacterial Toxins Nausea, Vomiting, and Abdominal Cramps within 1 Hour. Diarrhea within 30 Minutes to 12 Hours. Paresthesias within 1 to 3 Hours. Paresthesias within 3 to 30 Hours. Vomiting and Diarrhea in Less Than 24 Hours or Neurologic Symptoms in Less Than 48 Hours. Miscellaneous Mushroom Poisoning Syndromes with Onset within 2 Hours. Abdominal Cramps and Diarrhea within 6 to 24 Hours, Followed by Hepatorenal Failure. Vomiting and Diarrhea within 4 to 48 Hours, Followed by Renal Failure. Epidemiology Foods Nonfoodborne Transmission Vulnerable Populations Seasonality Geographic Location Epidemiologic Assessment Laboratory Diagnosis Therapy Surveillance Prevention Key References References Chapter 104 104 Tropical Sprue: Keywords Short View Summary Epidemiology Causes Clinical Manifestations Intestinal Abnormalities Histopathology Diagnosis Therapy References Chapter 105 105 Infectious Arthritis of Native Joints Keywords Short View Summary Acute Bacterial Arthritis Nongonococcal Arthritis Pathophysiology Microbiology Clinical Manifestations Radiographic Features Gonococcal Arthritis Pathogenesis Clinical Manifestations Management Initial Approach to the Patient Differential Diagnosis Therapy Viral Arthritis Chronic Infectious Arthritis Fungal Arthritis Therapy Mycobacterial Arthritis Septic Bursitis Key References References Chapter 106 106 Osteomyelitis Keywords Short View Summary Classification Lessons From Experimental Models General Principles Osteomyelitis after a Contaminated Open Fracture Vertebral Osteomyelitis and Spondylodiskitis Osteomyelitis in Patients with Diabetes Mellitus or Vascular Insufficiency Acute Hematogenous Osteomyelitis SAPHO Syndrome and Chronic Recurrent Multifocal Osteomyeltis Other Forms of Osteomyelitis: Specific Hosts, Unusual Locations, or Unusual Organisms Osteitis Pubis Osteomyelitis of the Clavicle Osteomyelitis in Hemodialysis Patients Osteomyelitis in Patients with Sickle Cell Disease Gaucher’s Disease Osteomyelitis in Injection Drug Users Skeletal Mycobacterial Infection Fungal Osteomyelitis Brodie’s Abscess Culture-Negative Osteomyelitis Summary Key References References Chapter 107 107 Orthopedic Implant–Associated Infections Keywords Short View Summary Periprosthetic Joint Infection Definition Pathogenesis Classification Risk Factors Patient Characteristics Surgery-Related Risk Factors Postoperative-Related Factors Risk during Bacteremia Microbiology Clinical Manifestations and Differential Diagnosis Acute Periprosthetic Joint Infection Chronic Periprosthetic Joint Infection Diagnostic Procedures Blood Tests Synovial Fluid Cell Counts Synovial Fluid Culture Intraoperative Samples for Culture and Histopathology Novel Diagnostic Procedures Sonication Molecular Diagnostics Bead Mill Processing Imaging Procedures Positron Emission Tomography Treatment Concepts General Aspects Surgical Interventions Débridement with Retention of Implant One-Stage Exchange Two-Stage Exchange Antimicrobial Therapy Internal Fixation–Associated Infection Definition Incidence of Infection Pathogenesis and Classification Microbiology Clinical Manifestations Diagnostic Procedures Microbiology and Histopathology Imaging Treatment Concepts General Aspects Systemic Antimicrobial Therapy Local Antimicrobial Therapy Surgical Interventions Plate-Associated Osteomyelitis Intramedullary Nail–Associated Osteomyelitis Pin-Tract Infection Prevention in Orthopedic Surgery Perioperative Antimicrobial Prophylaxis Arthroplasty and Closed Fractures Open Fractures Prevention of Hematogenous Infection Key References References Chapter 108 108 Genital Skin and Mucous Membrane Lesions Keywords Short View Summary History of Presentation Clinical Manifestations Location Pain, Dysesthesias, and Systemic Symptoms Lymphadenopathy Lesion Morphology Duration Epidemiology Genital Lesions in Patients with Human Immunodeficiency Virus Laboratory Testing Therapy Other Management Issues Nonvenereal Genital Lesions Key References References Chapter 109 109 Urethritis Keywords Short View Summary Examination of the Urethra Examination of the Urethral Specimen Noninfectious Urethritis Infectious Urethritis Gonococcal and Nongonococcal Urethritis Etiology of Nongonococcal Urethritis Postgonococcal Urethritis Asymptomatic Urethral Infection Urethral Syndrome and Related Diseases of Women Complications of Urethritis Therapy Therapy for Sexual Partners of Men with Nongonococcal Urethritis Reactive Arthritis Clinical Manifestations Laboratory Findings Therapy Key References References Chapter 110 110 Vulvovaginitis and Cervicitis Keywords Short View Summary Vaginal Secretions Approach to the Patient History Age Mode of Onset Quantity of Discharge External Irritation Odor Abdominal Pain Sexual History Other Diseases Medications Examination Trichomoniasis Etiology and Pathogenesis Diagnosis Therapy Vulvovaginal Candidiasis Etiology and Pathogenesis Clinical Manifestations Diagnosis Therapy Bacterial Vaginosis Epidemiology Pathophysiology Diagnosis Therapy Desquamative Inflammatory Vaginitis Etiology and Pathogenesis Diagnosis Therapy Cervicitis Etiology and Pathogenesis Diagnosis Therapy Estrogen-Deficiency Vaginitis Etiology and Pathogenesis Diagnosis Therapy Vulvitis and Vestibulitis Vulvitis Etiology and Pathogenesis Diagnosis Therapy Vestibulitis Etiology and Pathogenesis Diagnosis Therapy Key References References Chapter 111 111 Infections of the Female Pelvis Keywords Short View Summary Intrapartum, Postpartum, and Postabortal Infections Postpartum Endometritis Refractory Postpartum Fever of Undetermined Origin Infections after Perineal Lacerations Postabortal Infections Surgical Site Infection after Gynecologic Surgery Pathogenesis Risk Factors Cuff Cellulitis Pelvic Abscess Osteomyelitis Pubis Pelvic Inflammatory Disease Risk Factors Diagnosis Management of Acute Pelvic Inflammatory Disease Management of Suspected Tubo-ovarian Abscess Sequelae Key References References Chapter 112 112 Prostatitis, Epididymitis, and Orchitis Keywords Short View Summary Anatomy and Physiology of the Testes and Male Accessory Sex Organs Host Defenses of the Male Lower Urogenital Tract Prostatitis Classification Acute Bacterial Prostatitis Chronic Bacterial Prostatitis Chronic Prostatitis/Chronic Pelvic Pain Syndrome Asymptomatic Inflammatory Prostatitis Granulomatous Prostatitis Prostatic Abscess Epididymitis Nonspecific Bacterial Epididymitis Sexually Transmitted Epididymitis Follow-up Orchitis Viral Orchitis Bacterial Orchitis Prostatitis, Epididymitis, and Orchitis in Men with HIV-1 Infection Urologic Manifestations Semen as a Vector for Human Immunodeficiency Virus Key References References Chapter 113 113 Introduction to Eye Infections Keywords Anatomy Types of Eye Infections Conjunctivitis Keratitis Endophthalmitis Uveitis Periorbital Infections Understanding the Ophthalmologist’s Note Visual Acuity and Measuring Low Vision Intraocular Pressure Ophthalmology Examination Case Example 1 Ophthalmologist’s Examination Discussion Case Example 2 Ophthalmologist’s Examination Discussion Conclusion Chapter 114 114 Microbial Conjunctivitis Keywords Short View Summary Conjunctivitis Anatomy and Physiology Clinical Presentation History and Physical Examination Eye Pain Itching Visual Acuity Periocular and Periorbital Skin Conjunctival Hyperemia Discharge Conjunctival Edema (Chemosis) and Conjunctivochalasis Conjunctival Papillae Conjunctival Follicles Membranes and Pseudomembranes Conjunctival Phlyctenules and Granulomas Corneal Involvement Preauricular Adenopathy Laboratory Evaluation Viral Conjunctivitis Adenoviral Conjunctivitis Pharyngoconjunctival Fever Epidemic Keratoconjunctivitis Acute Hemorrhagic Conjunctivitis Herpes Simplex Conjunctivitis Varicella and Herpes Zoster Conjunctivitis Variola (Smallpox) Conjunctivitis Vaccinia Conjunctivitis Other Viral Etiologies Chlamydial Conjunctivitis Chlamydia trachomatis Infection Chlamydia pneumoniae Infection Trachoma Adult Inclusion Conjunctivitis Treatment of Adult Inclusion Conjunctivitis Lymphogranuloma Venereum Bacterial Conjunctivitis Pathogenesis Acute (Mucopurulent) Bacterial Conjunctivitis Treatment of Acute Bacterial Conjunctivitis Hyperacute (Purulent) Bacterial Conjunctivitis Treatment of Hyperacute Bacterial Conjunctivitis Chronic Bacterial Conjunctivitis Treatment of Chronic Bacterial Conjunctivitis Neonatal Conjunctivitis Neonatal Chemical Conjunctivitis Neonatal Chlamydial Conjunctivitis Neonatal Gonococcal Conjunctivitis Nongonococcal Neonatal Bacterial Conjunctivitis Neonatal Viral (Herpetic) Conjunctivitis Parinaud’s Oculoglandular Conjunctivitis Parasitic Conjunctivitis Leishmaniasis and Microsporidia Other Parasites and Ectoparasites Fungal Conjunctivitis Noninfectious Vision-Threatening Conditions Associated with “Red Eye” Key References References Chapter 115 115 Microbial Keratitis Keywords Short View Summary Etiologic Agents and Risk Factors Microbial Agents Anatomic Protection Risk Factors Contact Lenses Laboratory Data and Clinical Response Clinical Presentation Eye Pain Conjunctival Injection and Discharge Corneal Infiltrate Epithelial Defect Stromal Suppuration Corneal Edema Corneal Neovascularization Intraocular Inflammatory Reaction Stromal Melting (Keratolysis) Laboratory Evaluation Stains and Media Inoculation Viral Cultures Bacterial Keratitis Etiology Pathogenesis Geographic Variation Gram-Positive Bacteria Gram-Negative Bacteria Mycobacteria Therapy for Bacterial Keratitis Immediate, Aggressive Therapy Hospital Admission Antibiotic Solutions Local and Systemic Administration Contact Lenses and Collagen Shields Unique Pharmacokinetics with Topical Antibiotics Initial Therapy Topical Fluoroquinolones Comparison of Fluoroquinolones and Fortified Antibiotics Proposed Therapy Guidelines Topical Corticosteroids Supportive Measures Chlamydial and Syphilitic Keratitis Ocular Associations with Chlamydia Syphilitic Keratitis (Interstitial Keratitis) Therapy for Chlamydial and Syphilitic Keratitis Therapy for Interstitial Keratitis (Syphilitic and Lyme Associated) Viral Keratitis Herpes Simplex Virus Primary Herpes Simplex Virus Keratitis Recurrent Keratitis Stromal Inflammation and Intraocular Reaction Neurotrophic Keratitis Varicella-Zoster Virus Herpes Zoster Ophthalmicus Clinical Manifestations of Herpes Zoster Ophthalmicus Corneal Anesthesia Ocular Complications with Vaccinia (Smallpox) Vaccination Vaccinia Keratitis Adenoviral Keratitis Differential Diagnosis of Epidemic Keratoconjunctivitis Therapy for Viral Keratitis Self-Limited Cases Therapy for Herpes Simplex Virus and Varicella-Zoster Virus Therapy for Ocular Vaccinia Therapy for Viral Keratoconjunctivitis Fungal Keratitis Mild Early Clinical Presentation Fusarium Keratitis Candida Keratitis Therapy for Fungal Keratitis Limited Therapy Options Parasitic Keratitis Acanthamoeba Keratitis Clinical Signs and Symptoms with Amebic Keratitis Onchocerciasis Leishmaniasis Microsporidia and Trypanosomes Therapy for Parasitic Keratitis Key References References Chapter 116 116 Endophthalmitis Keywords Short View Summary Categories Acute Postcataract Endophthalmitis Chronic Postcataract Endophthalmitis Postinjection Endophthalmitis Bleb-Related Endophthalmitis Post-traumatic Endophthalmitis Endogenous Bacterial Endophthalmitis Fungal Endophthalmitis Endogenous Candida Endophthalmitis Exogenous Candida Endophthalmitis Mold Endophthalmitis Diagnosis Therapy Acute Bacterial Endophthalmitis Chronic Postcataract Endophthalmitis Fungal Endophthalmitis Endogenous Candida Endophthalmitis Exogenous Candida Endophthalmitis Mold Endophthalmitis Visual Outcome Key References References Chapter 117 117 Infectious Causes of Uveitis Keywords Short View Summary Epidemiology Etiology and Pathophysiology General Clinical MANIFESTATIONS Clinical MANIFESTATIONS of Major Infectious Etiologies Anterior Uveitis Due to Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus Acute Retinal Necrosis Progressive Outer Retinal Necrosis Cytomegalovirus Retinitis Ocular Syphilis Ocular Tuberculosis Ocular Toxoplasmosis Ocular Toxocariasis Ocular Lyme Disease Chronic Endophthalmitis Due to Propionibacterium acnes or Candida Species Clinical MANIFESTATIONS of Uncommon Infectious Etiologies Cat-Scratch Disease West Nile Virus Leptospirosis Chikungunya Virus Brucellosis Whipple’s Disease Leprosy Presumed Ocular Histoplasmosis Syndrome Diagnosis of Infectious Uveitis Approach to the Patient with Uveitis Therapy Key References References Chapter 118 118 Periocular Infections Keywords Short View Summary Eyelid Infections Anatomy Hordeolum Chalazion Marginal Blepharitis Infections of the Lacrimal System Anatomy Dacryoadenitis Canaliculitis Dacryocystitis Preseptal Cellulitis and Orbital Infections Anatomy Epidemiology Etiology and Bacteriology Clinical Manifestations Preseptal and Orbital Cellulitis Orbital and Subperiosteal Abscesses Orbital Apex, Superior Orbital Fissure, and Cavernous Sinus Syndromes Cavernous Sinus Thrombophlebitis Laboratory and Radiologic Studies Therapy Key References References Chapter 119 119 Viral Hepatitis Keywords Short View Summary Acute Viral Hepatitis Clinical Manifestations Laboratory Features Prognosis of Acute Hepatitis Fulminant Hepatitis Complications of Acute Hepatitis Agents of Viral Hepatitis Hepatitis A Virus (also see Chapter 176) Hepatitis B Virus (also see Chapter 148) Hepatitis C Virus (also see Chapter 156) Hepatitis D Virus (also see Chapter 148) Hepatitis E Virus (also see Chapter 180) Diagnosis Differential Diagnosis Treatment Prevention Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Chronic Viral Hepatitis Chronic Hepatitis B Distinctions Based on Relative Levels of HBV Replication Distinctions Based on Epidemiologic Considerations Distinctions Based on Viral Variants Pathophysiology and Natural History Clinical Manifestations Treatment Interferon-Based Therapy for Chronic Hepatitis B Direct Oral Antiviral Agents Lamivudine. Adefovir Dipivoxil. Entecavir. Telbivudine. Tenofovir. Other Agents for Chronic Hepatitis B Optimal Use of Available Agents for Hepatitis B Recommendations for Therapy Choice of Antiviral Agents Special Patient Populations Pregnancy Liver Transplantation HIV Coinfection (also see Chapter 126) Immune-Complex Disease Oncology Patients Who Need Cytotoxic Chemotherapy Chronic Hepatitis D Treatment Chronic Hepatitis C Pathophysiology and Natural History Clinical Manifestations Hepatitis C Virus–HIV Coinfection (also see Chapter 126) Treatment Pegylated Interferon and Ribavirin: Standard of Care 2001 to 2011—Treatment Principles Established Tailored Therapy Clinical Benefits of Therapy First-Generation NS3-4A Protease Inhibitors for Chronic Hepatitis C: Boceprevir and Telaprevir—The New Standard of Care for Genotype 1, 2011 to 2013 Second-Generation NS3-4A Protease Inhibitor and First-Generation Nucleoside Polymerase Inhibitor for Chronic Hepatitis C: Simeprevir and Sofosbuvir—The New Standard of Care, 2014 Candidates for Therapy Special Patient Populations Liver Transplantation HIV Coinfection (also see Chapter 126) Immune-Complex Disease B-cell Lymphoma Future Therapies Chronic Hepatitis E Treatment Key References References Chapter 120 120 Global Perspectives on Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome Keywords Size of the Problem Western Europe Eastern Europe and Central Asia Sub-Saharan Africa Middle East and North Africa Asia Latin America and the Caribbean Dynamics of the Spread of Human Immunodeficiency Virus Modes of Transmission Determinants That Influence the Spread of Human Immunodeficiency Virus Sexual Behavior Male Circumcision Antiretroviral-Based Prevention Treatment as Prevention Combination Prevention Demography and Social Context Gender Stigma and Discrimination Impact of Prevention and Care Programs Impact of the AIDS Epidemic Global Responses to AIDS Key References References Chapter 121 121 Epidemiology and Prevention of Acquired Immunodeficiency Syndrome and Human Immunodeficiency Virus Infection Keywords HIV and AIDS Surveillance in the United States HIV Infection and AIDS in Adults Incidence and Prevalence of AIDS and HIV in the United States Serologic Monitoring of the HIV Epidemic Exposure Categories AIDS Trends Demographic Characteristics Geographic Distribution of AIDS Cases Clinical Manifestations of HIV Infection Spectrum and Progression of HIV Infection AIDS-Indicator Diseases HIV Infection and Tuberculosis Mortality of Persons with HIV Infections and AIDS AIDS in Children Modes of Transmission Sexual Transmission Infectiousness of the Source Partner Susceptibility of the Recipient Partner Transmission through Injection Drug Use Transmission by Blood and Other Tissues Perinatal Transmission Transmission of HIV in Health Care Settings Other Modes of Transmission HIV Infection and AIDS outside the United States HIV-2 Prevention of HIV Infection in the Community Prevention of Sexual Transmission Prevention of Transmission by Injection Drug Use Prevention of Transmission through Blood and Other Tissues Prevention of Transmission in the Health Care Setting Prevention of Perinatal Infection Counseling and HIV Antibody Testing Guidelines for HIV Counseling and Testing Key References References Chapter 122 122 Diagnosis of Human Immunodeficiency Virus Infection Keywords Short View Summary Background/Perspective Advances in Laboratory Science Advances in Guidelines, Recommendations, and Regulation HIV Diagnostic Terminology and Performance Characteristics Specific Laboratory Methods for Detection of HIV Infection Immune Responses to HIV HIV Screening Assays Serologic Techniques to Detect Anti-HIV Antibody Standard ELISA Assays Particle Agglutination Assays Alternative ELISA Formats: Simple/Rapid Tests Saliva as Source of Patient Material for ELISA Assay Urine as Source of Patient Material for ELISA Serologic Techniques to Screen for HIV Antigens Combined Antigen-Antibody Detection: Fourth-Generation Assays False-Positive and false-Negative Results in Serologic Screening Tests for HIV Antibody Nonserologic Techniques to Screen for HIV Hybridization and Amplification Assays to Detect HIV Nucleic Acids HIV Confirmatory Assays Western Blot HIV-1/2 ELISA Immunofluorescence Indirect Immunofluorescence Practical Implementation of HIV Diagnosis Test Setting, Consent, and Pretest Counseling HIV-1/2 Screening Phase HIV-1/2 Confirmation Phase Test Counseling Alternative Strategies for Screening/Confirmation HIV Detection Post-test Counseling and Linkage to Care Specific Circumstances and Special Populations HIV Testing in the Setting of Acute Retroviral Syndrome or Other Acute Illness Detection of HIV-2 and HIV-1/2 Dual Infections Detecting Non-B HIV-1 Types and Subtypes Other Than Subtype B Detecting HIV-1 Dual Infections HIV Testing during Pregnancy or at Delivery HIV in Perinatal Diagnosis (also see Chapter 129) HIV Testing for Blood Donor Screening HIV Testing in Tissue Procurement for Transplantation HIV Testing in Vaccine, Prevention, Postexposure, and Gene Therapy Studies HIV Infection but Viral RNA Less Than 50 Copies/mL: HIV Elite Controllers HIV Testing in Occupational Exposure HIV Testing in Idiopathic CD4 Lymphopenia Factitious HIV Infection and AIDS Phobia HIV Testing to Estimate Duration of Infection and Incidence Home Collection and Home Testing for HIV Other Human Retroviral Infections and New Retroviral Zoonoses Regulatory and Distribution Issues Conclusion Acknowledgments Key References References Chapter 123 123 The Immunology of Human Immunodeficiency Virus Infection Keywords Human Immunodeficiency Virus Entry and Dissemination Human Immunodeficiency Virus Receptors and Entry into Cells Dissemination of Human Immunodeficiency Virus Infection Human Immunodeficiency Virus–Specific Immune Responses Humoral Immune Responses Cellular Immune Responses Cytotoxic T Lymphocytes Soluble CD8+ T-Cell–Secreted Factors CD4+ T-Cell Responses Host Genetic Factors Long-Term Nonprogressors/Elite Controllers Host Immune Response Factors Virologic Factors Reservoirs of Human Immunodeficiency Virus Infection Latent Reservoirs of Human Immunodeficiency Virus Lymphoid Tissues Strategies for HIV Eradication Immune Dysfunction Caused by Human Immunodeficiency Virus Infection Lymphoid Tissues CD4+ T Cells Mechanisms of CD4+ T-Cell Depletion Increased Destruction Direct Infection. Apoptosis. Lymphocyte Turnover. Decreased Production Redistribution. CD8+ T Cells B Cells Natural Killer Cells Monocytes and Macrophages Dendritic Cells Role of Immune Activation in the Pathogenesis of Human Immunodeficiency Virus Infection Cytokines and Human Immunodeficiency Virus Disease: Dysregulation of Cytokine Production Role of Cytokines as Therapeutic Agents in Human Immunodeficiency Virus Infection Conclusions Key References References Chapter 124 124 General Clinical Manifestations of Human Immunodeficiency Virus Infection (Including Acute Retroviral Syndrome and Oral, Cutaneous, Renal, Ocular, Metabolic, and Cardiac Diseases) Keywords Short View Summary History Classification of HIV Infection Natural History of HIV Infection Effect of Antiretroviral Therapy on Natural History of HIV Infection Clinical Manifestations Acute Retroviral Syndrome Persistent Generalized Lymphadenopathy Constitutional Disease and Wasting Metabolic and Endocrine Abnormalities Oral Disease Oral Candidiasis Oral Hairy Leukoplakia Gingivitis and Periodontitis Oral Ulcers Other Oral Lesions Musculoskeletal Complications Cutaneous Manifestations Viral Infections of the Skin and Mucous Membranes Bacillary Angiomatosis Kaposi Sarcoma Other Cutaneous Manifestations Scabies Renal Disease Ocular Complications Cardiac Manifestations Hematologic Manifestations Immune Reconstitution Syndromes Tuberculosis Mycobacterium avium Complex Disease Cytomegalovirus Disease Infection with Varicella-Zoster Virus Viral Hepatitis Other Diseases Key References References Chapter 125 125 Pulmonary Manifestations of Human Immunodeficiency Virus Infection Keywords Short View Summary Epidemiology Differential Diagnosis Clinical or Laboratory Stage of Immunosuppression Tempo of the Illness Receipt and Type of Pneumocystis Prophylaxis Receipt of Antiretroviral Therapy History of Opportunistic Processes Injection Drug Use and Smoking Local Epidemiology or Past Residence Characteristic Radiographic Findings Triage of Patients: Infection Control Issues Diagnostic Tests Specific Pathogens Pneumocystis jirovecii Pneumonia Bacterial Pneumonia Mycobacterial Pneumonia Fungal Pneumonia Viral Pneumonia Parasitic Pneumonia Neoplastic and Other Noninfectious Pulmonary Complications of Human Immunodeficiency Virus Infection Treatment Key References References Chapter 126 126 Gastrointestinal, Hepatobiliary, and Pancreatic Manifestations of Human Immunodeficiency Virus Infection Keywords Short View Summary Disorders of the Esophagus Disorders of the Stomach Disorders of the Biliary Tree and Gallbladder Disorders of the Liver Disorders of the Pancreas Disorders of the Small and Large Intestine References Chapter 127 127 Neurologic Diseases Caused by Human Immunodeficiency Virus Type 1 and Opportunistic Infections Keywords Short View Summary Principal Neurologic Manifestations of HIV Type 1 Infection Meningeal Syndrome Patient Otherwise Asymptomatic, CD4+ T-Lymphocyte Counts Greater Than 200 cells/µL: Aseptic Meningitis Clinical Presentation. Laboratory Investigations. Treatment. Patient at Any Stage of HIV Type 1 Infection and CD4+ T-Lymphocyte Counts at Any Level: Syphilitic Meningitis Clinical Presentation. Laboratory Investigations. Treatment. Patient with AIDS, CD4+ T-Lymphocyte Counts of Less Than 200 Cells/µL: Cryptococcal Meningitis Clinical Presentation. Laboratory Investigations. Treatment. Differential Diagnosis of Meningitis Cognitive and Motor Syndromes HIV Type 1 Associated Neurocognitive Disorder Clinical Presentation. Laboratory Investigations. Imaging Studies. Brain Biopsy and Histologic Analysis. Treatment. Central Nervous System Mass Lesions Toxoplasma Encephalitis Clinical Presentation. Laboratory Investigations. Imaging Studies. Brain Biopsy. Treatment. Secondary Prophylaxis. Primary Central Nervous System Lymphoma Clinical Presentation. Laboratory Investigations. Imaging Studies. Brain Biopsy. Treatment. Progressive Multifocal Leukoencephalopathy Clinical Presentation. Laboratory Investigations. Imaging Studies. Brain Biopsy. Treatment. Inflammatory Progressive Multifocal Leukoencephalopathy Cytomegalovirus Encephalitis Clinical Presentation. Laboratory Investigations. Imaging Studies. Brain Biopsy. Treatment. Miscellaneous Mass Lesions and Rationale for Brain Biopsy Spinal Syndrome Vacuolar Myelopathy Clinical Presentation. Laboratory Investigations. Imaging Studies. Histologic Studies. Treatment. Differential Diagnosis of a Noncompressive Myelopathy Peripheral Nervous System Syndromes HIV-Associated Neuropathies Inflammatory Demyelinating Polyneuropathy Laboratory Investigations. Electrophysiologic Studies. Nerve Biopsy. Treatment. Distal Sensory Polyneuropathy HIV Associated. Clinical Presentation. Laboratory Investigations. Electrophysiologic Studies. Nerve and Skin Biopsy. Nucleoside Neuropathy Clinical Presentation. Laboratory Investigations. Treatment. Mononeuritis Multiplex Clinical Presentation. Laboratory Investigations. Electrophysiologic Studies. Nerve Biopsy. Treatment. Progressive Polyradiculopathy Clinical Presentation. Laboratory Investigations. Electrophysiologic Studies. Nerve Biopsy. Treatment. Diffuse Infiltrative Lymphocytosis Syndrome-Associated Neuropathy Clinical Presentation. Electrophysiologic Studies. Nerve Biopsy. Treatment. Amyotrophic Lateral Sclerosis-Like Syndrome Musculoskeletal Syndromes Myopathy Clinical Presentation. Laboratory Investigations. Electrophysiologic Studies. Muscle Biopsy. Treatment. Other Musculoskeletal Conditions Associated with HIV Seizures Temporal Trends and Aging in Neurologic Manifestations of HIV Infection Key References References Chapter 128 128 Human Immunodeficiency Virus Infection in Women Keywords Epidemiology United States Worldwide Transmission Heterosexual Transmission Efficiency of Transmission Associated Factors HIV Infection within the Genital Tract Strategies to Prevent Heterosexual Transmission Perinatal Transmission Preconception Counseling and Care for HIV-Infected Women of Childbearing Age Timing of Transmission Risk Factors Impact of Pregnancy on HIV Infection Impact of HIV Infection on Pregnancy Outcome Use of Antiretroviral Drugs in Pregnancy for Maternal Health and to Reduce Perinatal Transmission Use of Antiretroviral Drugs to Decrease Perinatal Transmission Potential Mechanisms of Antiretroviral Drugs to Reduce Perinatal Transmission Recommended Guidelines on the Use of Antiretroviral Agents in HIV-Infected Adults and in Pregnancy Management of Pregnant HIV-Infected Women Antepartum Care HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy Stopping Antiretroviral Therapy during Pregnancy HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment but Are Not Currently Receiving Medication Monitoring of the Woman and Fetus during Pregnancy Teratogenicity Intrapartum Antiretroviral Therapy/Prophylaxis Postpartum Follow-up of HIV-Infected Women Clinical Manifestations and Natural History of HIV Infection in Women Opportunistic Processes and Nongynecologic Malignancies Gynecologic Infections and Disease Human Papillomavirus Infections and Disease Vaginal Infections Bacterial Vaginosis Vulvovaginal Candidiasis Trichomonal Vaginitis Pelvic Inflammatory Disease Genital Ulcer Disease Cervicovaginal HIV-1 RNA Shedding Sex Hormones, Ovulation, and Menstrual Function Fertility Issues Contraception and Sexually Transmitted Infection Protection Sex Differences in HIV-1 RNA Levels, HIV Progression, and Antiretroviral Treatment Response Sex Influence on Antiretroviral Pharmacokinetics and Adverse Events Metabolic Complications Management Issues Key References References Chapter 129 129 Pediatric Human Immunodeficiency Virus Infection Keywords Short View Summary Current Epidemiology of Domestic Pediatric and Adolescent HIV Infection Remaining Challenges in Domestic Pediatric HIV Infection Elimination of New Pediatric HIV Infection Maternal Determinants of Mother-to-Child Transmission Postpartum Mother-to-Child Transmission Elimination of Mother-to-Child Transmission Prevention of Adolescent HIV Infection Issues in the Care of Aging HIV-Infected Youth Disclosure of the HIV Diagnosis Care Refusal and Low Adherence among HIV-Infected Youth Transition of HIV-Infected Youth from the Pediatric Care Model to the Adult Care Model Adult Complications of Perinatal HIV Infection Key References References Chapter 130 130 Antiretroviral Therapy for Human Immunodeficiency Virus Infection Keywords Short View Summary Antiretroviral Agents Nucleoside and Nucleotide Reverse-Transcriptase Inhibitors Zidovudine Stavudine Didanosine Lamivudine/Emtricitabine Abacavir Tenofovir Non-nucleoside Reverse-Transcriptase Inhibitors Nevirapine Efavirenz Delavirdine Etravirine Rilpivirine Protease Inhibitors Ritonavir Saquinavir Indinavir Nelfinavir Fosamprenavir Lopinavir/Ritonavir Atazanavir Tipranavir Darunavir Entry Inhibitors Enfuvirtide Maraviroc Integrase Strand Transfer Inhibitors Raltegravir Elvitegravir Dolutegravir Initiating Antiretroviral Therapy When to Begin Therapy? What to Begin With? The Dual-NRTI Backbone Initial NNRTI-Based versus PI-Based Therapy versus INSTI-Based Therapy Initial PI-Based Regimens Initial NNRTI-Based Regimens Initial Integrase Inhibitor-Based Therapy Triple NRTI and Four-Drug Therapy Interrupting Therapy Laboratory Testing during Antiretroviral Therapy CD4 T-cell Counts HLA-B*5701 Screening Plasma Viral Load Monitoring HIV Drug Resistance Testing Determining HIV Co-receptor Usage Changing Therapy Special Circumstances Preexposure Prophylaxis Postexposure Prophylaxis Occupational HIV Exposures Nonoccupational HIV Exposures Conclusions and Future Directions Key References References Chapter 131 131 Management of Opportunistic Infections Associated with Human Immunodeficiency Virus Infection Keywords Short View Summary Prospective Monitoring Spectrum of Opportunistic Pathogens Management of Antiretroviral Therapy for Patients with Acute Opportunistic Infection Infections Due to Pathogens That are Not Opportunistic Drug Interactions General Principles of Management Opportunistic Infections Pneumocystis jirovecii Pneumonia Toxoplasma gondii Herpes Simplex Virus and Varicella-Zoster Virus Cytomegalovirus Epstein-Barr Virus and Human Herpesvirus 6 and 7 Progressive Multifocal Leukoencephalopathy Candida Species Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis/posadasii Bacterial Pneumonia Mycobacterium Species Infection Mycobacterium tuberculosis Mycobacterium avium Complex Enteric Pathogens: Salmonella, Shigella, and Campylobacter Species and Clostridium difficile Cryptosporidium, Cystoisospora, cyclospora, and Microsporida Species Treponema pallidum Bartonella Species Kaposi Sarcoma and Human Herpesvirus 8 Viral Hepatitis Key References References Chapter 132 132 Vaccines for Human Immunodeficiency Virus Type 1 Infection Keywords Immune Responses to HIV Infection Cell-Mediated Immune Responses Neutralizing Antibody Responses Types of Candidate HIV-1 Vaccines Live Attenuated Virus Vaccines Whole Killed Virus Vaccines Envelope Proteins Synthetic Peptides Internal or Core Proteins Live Vectors DNA Vaccines Animal Models Human Trials Phase I Studies Envelope Proteins Synthetic Peptides Poxvirus Vectors Adenovirus Vectors DNA Vaccines Phase II Clinical Studies Phase IIb and III Efficacy Studies Summary Key References References Chapter 133 133 Chronic Fatigue Syndrome Keywords Short View Summary History Epidemiology Etiology and Pathogenesis Role of Infection Role of the Autonomic Nervous System Role of the Immune System Role of the Central Nervous System Role of the Genome Clinical Manifestations Laboratory Findings Management General Principles Pharmacologic Therapy Nonpharmacologic Therapy Summary Key References References Chapter 134 134 Biology of Viruses and Viral Diseases Keywords History Virus Structure and Classification Virus–Cell Interactions Attachment Penetration and Disassembly Genome Replication Cell Killing Antiviral Drugs Virus–Host Interaction Entry Spread Tropism Persistent Infections Viruses and Cancer Viral Virulence Determinants Host Responses to Infection Key References References Chapter 135 135 Orthopoxviruses: Keywords Short View Summary Background Morphology and Chemical Structure Pathogenesis Vaccinia (Smallpox Vaccine) Immunity Resulting from Vaccination Complications Resulting from Vaccination Vaccinia Virus as a Zoonosis Variola (Smallpox) Monkeypox Pathogenesis Clinical Manifestations Diagnosis Epidemiology and Control Cowpox Clinical Manifestations Orthopoxvirus Laboratory Diagnostics Therapy: Orthopoxviruses Key References References Chapter 136 136 Other Poxviruses That Infect Humans: Keywords Short View Summary Parapoxviruses Morphology and Composition of the Agent Pathogenesis and Immune Response Clinical Manifestations Diagnosis Epidemiology Therapy Molluscum Contagiosum Description of the Agent Pathogenesis and Pathology Clinical Manifestations Diagnosis Epidemiology and Control Therapy Yatapoxviruses Tanapox Pathophysiology and Clinical Manifestations Diagnosis Epidemiology and Control Yaba Monkey Tumor Virus Clinical Manifestations Key References References Chapter 137 137 Introduction to Herpesviridae Keywords Classification Genome Structure and Proteins Virus Replication Virus Latency and Reactivation Pathogenesis Epidemiology Clinical Syndromes Immunity Oncogenesis Diagnosis Therapy Prevention Key References References Chapter 138 138 Herpes Simplex Virus Keywords Short View Summary Description of the Virus Structure Replication Molecular Features of Latency Epidemiology HSV-1 HSV-2 HSV-2 Risk Factors Transmission Pathogenesis Primary Infection Ganglionic Immunity Mucosal Immunity Viral and Host Factors Impacting Pathogenesis and Disease Severity Spectrum of Diseases Caused by HSV Orofacial HSV Infection Genital HSV Infection Complications of Genital HSV Infection Aseptic Meningitis/Transverse Myelitis/Sacral Radiculopathy Extragenital Lesions Disseminated Infection Superinfection Recurrent Mucocutaneous HSV Infections Frequency of Reactivation and Recurrence Herpetic Whitlow Herpes Gladiatorum Eye Infections HSV Encephalitis Visceral and Pulmonary HSV Infections Interactions between Genital HSV Infection and HIV Infection HSV Infections in Immunocompromised Hosts Not Infected with HIV Neonatal Herpes HSV Infection in Pregnancy Clinical Course of Genital Herpes in Pregnancy Prevention of HSV Acquisition in Pregnancy by Use of Antiviral Agents Diagnosis of HSV Infections Therapy for HSV Infections Counseling and Prevention Key References References Chapter 139 139 Chickenpox and Herpes Zoster (Varicella-Zoster Virus) Keywords Short View Summary Historical Overview The Pathogen and Its Replication Epidemiology of Varicella-Zoster Virus Infections Chickenpox Herpes Zoster Pathogenesis Clinical Manifestations Chickenpox Chickenpox in the Immunocompromised Patient Herpes Zoster Diagnosis Therapy Prevention Key References References Chapter 140 140 Cytomegalovirus (CMV) Keywords Short View Summary Description of the Pathogen Laboratory Diagnosis Cultivation of Cytomegalovirus Cytomegalovirus Mononucleosis Associated Complications Interstitial Pneumonia Hepatitis Guillain-Barré Syndrome Meningoencephalitis Myocarditis Thrombocytopenia and Hemolytic Anemia Skin Eruptions Cytomegalovirus Infection in Patients with Acquired Immunodeficiency Syndrome Central Nervous System Gastrointestinal Tract Antiviral Therapy Ganciclovir Valganciclovir Resistance to Ganciclovir Foscarnet Cidofovir Cross-Resistance to Antiviral Drugs in Cytomegalovirus Clinical Isolates Investigational Antiviral Agents Maribavir Letermovir CMX001 Prevention of Cytomegalovirus Disease Cytomegalovirus Infection in Transplantation Patients Cytomegalovirus Infection Acquired from Donated Organs Immunosuppressive Therapy Hematopoietic Stem Cell Transplantation Liver Transplantation Kidney Transplantation Drug Resistance in Solid-Organ Recipients Cytomegalovirus Infection and Cardiovascular Disease Congenital Cytomegalovirus Infection Cytomegalovirus Infection in Pregnant Women Cytomegalovirus Vaccine Prospects Key References References Chapter 141 141 Epstein-Barr Virus (Infectious Mononucleosis, Epstein-Barr Virus–Associated Malignant Diseases, and Other Diseases) Keywords Short View Summary History Description of Epstein-Barr Virus Physical Properties Life Cycle Latent Infection and Growth Transformation Lytic Infection Epidemiology Serum Antibody Prevalence Incidence of Infection Methods of Spread Public Health Impact Pathogenesis Host Immune Response Histopathologic Findings Clinical Manifestations Infectious Mononucleosis (Primary Infection) Spectrum of Illness Symptoms and Signs Complications Hematologic Splenic Rupture Neurologic Hepatic Renal Cardiac Pulmonary Death Clinical Course X-Linked Lymphoproliferative Disease Other Genetic Predispositions to Severe Epstein-Barr Virus Infection Chronic Active Epstein-Barr Virus Infection Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis Oral Hairy Leukoplakia Epstein-Barr Virus–Associated Malignant Diseases Lymphoproliferative Disease Burkitt’s Lymphoma Hodgkin’s Lymphoma Nasopharyngeal Carcinoma Gastric Carcinoma Other Malignant Diseases Multiple Sclerosis and Other Autoimmune Diseases Laboratory Diagnosis Infectious Mononucleosis Hematologic Findings Heterophile Antibodies Epstein-Barr Virus–Specific Antibodies Culture of Epstein-Barr Virus Epstein-Barr Virus Viral Load Other Laboratory Abnormalities Post-Transplant Lymphoproliferative Disease Nasopharyngeal Carcinoma Central Nervous System Lymphoma in Acquired Immunodeficiency Syndrome Differential Diagnosis of Infectious Mononucleosis Therapy Infectious Mononucleosis Supportive Antiviral Agents Corticosteroids Lymphoproliferative Disease Epstein-Barr Virus Targeted Therapy in Associated Malignant Diseases Oral Hairy Leukoplakia Prevention Public Health Measures Vaccine Key References References Chapter 142 142 Human Herpesvirus Types 6 and 7 (Exanthem Subitum) Keywords Short View Summary Human Herpesvirus Type 6 History Description of the Virus Epidemiology Pathogenesis Clinical Manifestations Infantile Fever and Seizures Exanthem Subitum (Roseola Infantum or Sixth Disease) Other Neurologic Symptoms Associated with HHV-6 Infectious Mononucleosis Other Complications in Healthy Persons Congenital Infection Infection in the Immunocompromised Host Laboratory Diagnosis Healthy Persons Immunocompromised Persons Therapy Human Herpesvirus Type 7 History Description of the Virus Epidemiology Pathogenesis Clinical Manifestations Laboratory Diagnosis Therapy Key References References Chapter 143 143 Kaposi’s Sarcoma–Associated Herpesvirus (Human Herpesvirus 8) Keywords Short View Summary History Classification and Biology Pathogenesis Epidemiology Clinical Manifestations Primary Infection Kaposi’s Sarcoma Primary Effusion Lymphoma Multicentric Castleman’s Disease Other Syndromes Therapy and Prevention Key References References Chapter 144 144 Herpes B Virus Keywords Short View Summary History Description of the Virus Epidemiology Pathogenesis Clinical Manifestations Laboratory Diagnosis After Exposure Postexposure Evaluation and Prophylaxis Diagnosis of Herpes B Virus Disease Therapy Prevention References Chapter 145 145 Adenoviruses Keywords Short View Summary Description of the Pathogen Interactions with the Host Epidemiology Clinical Syndromes Respiratory Tract Disease Ocular Disease Gastrointestinal Tract Disease Genitourinary Tract Disease Central Nervous System Disease Other Clinical Syndromes Infections in Immunocompromised Patients Hematopoietic Stem Cell Transplant Recipients Solid Organ Transplant Recipients HIV/AIDS Patients Diagnosis Therapy Prevention Adenoviruses as Vectors for Gene Therapy and Vaccination Key References References Chapter 146 146 Papillomaviruses Keywords Short View Summary Virology Epidemiology Incidence and Prevalence Transmission Association between Human Papillomavirus and Malignant Diseases Pathogenesis Clinical Manifestations Cutaneous Warts Epidermodysplasia Verruciformis Anogenital Warts Recurrent Respiratory Papillomatosis Other Human Papillomavirus Infections Diagnosis Therapy Cutaneous Warts Anogenital Warts Other Warts Prevention Key References References Chapter 147 147 JC, BK, and Other Polyomaviruses: Keywords Short View Summary Virology History Epidemiology Genome Receptors and Cell Entry JC Virus BK Virus New Human Polyomaviruses Progressive Multifocal Leukoencephalopathy and Other JC Virus–Associated Syndromes Epidemiology Pathogenesis Clinical Manifestations Classic Progressive Multifocal Leukoencephalopathy Progressive Multifocal Leukoencephalopathy–Immune Reconstitution Inflammatory Syndrome JC Virus Granule Cell Neuronopathy JC Virus Encephalopathy JC Virus Meningitis Diagnosis Imaging Brain Biopsy Cerebrospinal Fluid Polymerase Chain Reaction Assay Prognosis Therapy Nephropathy and Other BK Virus–Associated Diseases Epidemiology Pathogenesis Clinical Manifestations Nephropathy Ureteral Stenosis Hemorrhagic Cystitis Infections Outside the Renal System Diagnosis Urine Polymerase Chain Reaction Assay Renal Biopsy Plasma Polymerase Chain Reaction Assay Prognosis Therapy Nephropathy Ureteral Stenosis Hemorrhagic Cystitis Key References References Chapter 148 148 Hepatitis B Virus and Hepatitis Delta Virus Keywords Short View Summary Introduction Historical Background and Classification Biology Attachment, Entry, and Hepatotropism Viral Genome Transcription Translation Replication HBx Morphogenesis and Assembly Natural History and Pathogenesis of Disease Natural History Pathogenesis Acute Hepatitis B Chronic Hepatitis B Hepatocellular Carcinoma Epidemiology of Hepatitis B Routes of Transmission Clinical Manifestations and Prognosis Acute Hepatitis B Fulminant Hepatitis Chronic Hepatitis B Pre-core or HBE-Negative Mutants Prognosis of Untreated Chronic Hepatitis B Extrahepatic Manifestations of Hepatitis B Clinical Manifestations and Natural History in Special Hosts Individuals with HIV Infection Hepatitis B after Liver Transplantation Hepatitis B after Other Types of Transplantation Coinfection with Hepatitis C Screening and Diagnosis of HBV Infection Acute Hepatitis Past Hepatitis B Infection and Vaccination Chronic Hepatitis B Infection Measures of Hepatitis B Replication Isolated Anti-HBc Management of Hepatitis B Acute Hepatitis B Chronic Hepatitis B Selection of Patients for Treatment Interferon Nucleoside and Nucleotide Analogues Lamivudine Adefovir Entecavir Telbivudine Tenofovir Disoproxil Fumarate Other Agents and Combination Therapy Viral Resistance Monitoring and Treatment Duration of Nucleos(t)ide Therapy Management in Special Populations Liver Transplantation Human Immunodeficiency Virus Recipients of Immunosuppressive Therapies Treatment of HBV during Pregnancy Other Management Issues in Chronic Hepatitis B Hepatitis A Vaccination Screening and Vaccination of Contacts Surveillance for Hepatocellular Carcinoma Prevention of Hepatitis B Virus Infection Active Immunization Indications for Vaccination Dose Regimen Efficacy Durability of Response Postexposure Immunoprophylaxis Prevention of Perinatal Transmission Hepatitis B Surface Antigen Escape Mutants Hepatitis Delta Virus Hepatitis Delta Antigen Hepatitis D Virus RNA Genome and Replication Pathogenesis Epidemiology of Delta Hepatitis Clinical Manifestations of Hepatitis D Treatment of Hepatitis D Acknowledgments Key References References Chapter 149 149 Human Parvoviruses, Including Parvovirus B19V and Human Bocaparvoviruses Keywords Short View Summary Parvovirus B19 The Virus Pathogenesis Epidemiology Prevalence and Incidence Mechanism and Routes of Transmission Clinical Manifestations Erythema Infectiosum Arthropathy Transient Aplastic Crisis Pure Red Cell Aplasia Virus-Associated Hemophagocytic Syndrome Fetal Infection (Hydrops Fetalis and Miscarriage) Other Disease Manifestations Immune Response Diagnosis Therapy Prevention and Vaccination Other Human Parvoviruses Human Dependoparvoviruses Human Bocaparvoviruses Parv4 Key References References Chapter 150 150 Orthoreoviruses and Orbiviruses Keywords Short View Summary Orthoreoviruses Background and Epidemiology Clinical Disease Respiratory Tract Manifestations Gastrointestinal and Hepatobiliary Manifestations Central Nervous System Manifestations Reovirus as an Oncolytic Agent Orbiviruses Background and Epidemiology Clinical Disease Clinical Manifestations of Specific Agents Kemerovo Virus Antigenic Complex Oklahoma Tick Fever Orungo Virus Lebombo Virus Changuinola Virus African Horse Sickness Virus Diagnosis Key References References Chapter 151 151 Coltiviruses and Seadornaviruses Keywords Short View Summary Coltiviruses Colorado Tick Fever Virus Epidemiology Clinical Features Laboratory and Diagnostic Findings Therapy Salmon River Virus Eyach Virus Seadornaviruses Banna Virus Epidemiology and Clinical Features Key References References Chapter 152 152 Rotaviruses Keywords Short View Summary History and Overview Viral Structure and Replication Clinical Manifestations Pathogenesis Serologic Classification Epidemiology Immunity Diagnosis Therapy Immunization Acknowledgment Key References References Chapter 153 153 Alphaviruses Keywords Short View Summary History Pathogens Epidemiology Encephalitis-Causing Alphaviruses Alphaviruses Causing Fever, Rash, and Polyarthritis Chikungunya Virus O’nyong-nyong Virus Sindbis Virus Ross River Virus Mayaro Virus Pathogenesis Encephalitis Clinical Manifestations Alphaviruses Causing Encephalitis Alphaviruses Causing Fever, Rash, and Polyarthritis Diagnosis Therapy and Prevention Key References References Chapter 154 154 Rubella Virus (German Measles) Keywords Short View Summary Epidemiology Transmission of Rubella Maintenance of Immunity to Rubella Pathogenesis Clinical Manifestations Postnatal Rubella Complications of Postnatal Rubella Congenital Rubella Syndrome Diagnosis Therapy Vaccination Against Rubella Complications of Vaccination Efficacy of Vaccination Effects of Rubella Vaccine on the Fetus Key References References Chapter 155 155 Flaviviruses (Dengue, Yellow Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-Borne Encephalitis, Kyasanur Forest Disease, Alkhurma Hemorrhagic Fever, Zika) Keywords Short View Summary History Yellow Fever Dengue Japanese Encephalitis West Nile St. Louis Encephalitis Tick-Borne Encephalitis Alkhurma Hemorrhagic Fever Virus Kyasanur Forest Disease Virus Zika Virus Pathogens Epidemiology Yellow Fever Dengue Japanese Encephalitis West Nile St. Louis Encephalitis Tick-Borne Encephalitis Alkhurma Hemorrhagic Fever Virus Kyasanur Forest Disease Virus Zika Virus Pathogenesis Yellow Fever Dengue and Dengue Hemorrhagic Fever Flavivirus Encephalitis Clinical Manifestations Yellow Fever Dengue Fever and Dengue Hemorrhagic Fever Japanese Encephalitis West Nile St. Louis Encephalitis Tick-Borne Encephalitis Alkhurma Hemorrhagic Fever Virus Kyasanur Forest Disease Virus Zika Virus Laboratory Diagnosis Prevention and Therapy Yellow Fever Dengue and Dengue Hemorrhagic Fever Flavivirus Encephalitis Other Flavivirus Infections Murray Valley Encephalitis Rocio Encephalitis Omsk Hemorrhagic Fever Less Commonly Recognized Flavivirus Infections Acknowledgments Key References References Chapter 156 156 Hepatitis C Keywords Short View Summary Non-A, Non-B Viral Hepatitis and Hepatitis C Hepatitis C Virus Virion Properties and Classification Organization of the HCV Genome Nontranslated RNA Segments Polyprotein Structural Proteins p7 and NS2 Proteins Nonstructural Proteins Involved in RNA Replication Replication Genetic Diversity Quasispecies Variation HCV Genotypes Viral Tropism Experimental Models Autonomously Replicating Viral Replicons and Genome-Length RNAs Propagation of Virus in Cell Cultures Animal Models Natural History and Pathogenesis Viral Persistence Innate Immunity Humoral Immunity Cellular Immunity Disease Progression Hepatic Fibrosis Hepatocellular Carcinoma Clinical Manifestations of HCV Infection Acute Hepatitis C Fulminant Hepatitis C Chronic Hepatitis C Hepatocellular Carcinoma Extrahepatic Manifestations of HCV Infection Laboratory Assessment of HCV Infection Screening Serology RNA Detection Genotype Other Laboratory Testing Clinical Application of Tests for HCV Liver Staging Liver Biopsy Noninvasive Blood Markers of Hepatic Fibrosis Radiographic Tests Approach to Staging Liver Disease Epidemiology of Hepatitis C Prevalence of HCV Incidence and Transmission of HCV Biologic Basis of Transmission Percutaneous Transmission Nosocomial Infection Sexual Transmission Maternal-Infant Transmission Transmission Cofactors Treatment of Chronic Hepatitis C Treatment Responses Virologic Responses Histologic and Clinical Responses to Therapy Medications Interferon-α λ1 Interferon Ribavirin HCV Protease Inhibitors Nucleos(t)ide and Non-nucleoside Polymerase Inhibitors NS5A Targeting Drugs Other Antiviral Targets Treatment of Chronic Hepatitis C History and Progress Initial Treatment of Chronic HCV Infection in 2013 Response Indicators Re-treatment of Chronic HCV Infection in 2013 Adverse Reactions Antiviral Resistance Treatment Trends Anticipated Interferon-Based Treatments Interferon-Sparing HCV Treatment Recommended Treatments for Chronic Hepatitis C as of January 2014 Selection of Patients for Treatment Initial Treatment and Re-treatment of Chronic Hepatitis C Treatment of Acute Hepatitis C Prevention Preexposure Prevention Postexposure Prevention HIV Coinfection Epidemiology and Natural History Epidemiology of Coinfection Impact of HIV on the Course of Hepatitis C Infection Impact of HCV on the Course of HIV Infection HCV Infection and Antiretroviral Therapy Pathogenesis Diagnosis and Treatment of HCV in HIV-Infected Persons Serologic Testing Treatment of HCV Infection in HIV-Infected Persons Selection of Patients Treatment Trends for HIV/ HCV-Coinfected Persons Acknowledgment Key References References Chapter 157 157 Coronaviruses, Including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) Keywords Short View Summary History Respiratory Coronaviruses and Severe Acute Respiratory Syndrome Gastrointestinal Coronaviruses and Toroviruses Description of the Pathogens Epidemiology Community-Acquired Respiratory Coronaviruses Middle East Respiratory Syndrome Coronavirus Severe Acute Respiratory Syndrome Coronavirus Gastrointestinal Coronaviruses Pathogenesis Community-Acquired Respiratory Coronaviruses SARS-CoV and MERS-CoV Clinical Manifestations Community-Acquired Respiratory Coronaviruses Middle East Respiratory Syndrome Coronavirus Severe Acute Respiratory Syndrome Coronavirus Gastrointestinal Coronaviruses Neurologic Syndromes Laboratory Diagnosis Respiratory Coronaviruses Middle East Respiratory Syndrome Coronavirus Severe Acute Respiratory Syndrome Coronavirus Gastrointestinal Coronaviruses Therapy Prevention Key References References Chapter 158 158 Parainfluenza Viruses Keywords Short View Summary Microbiology Pathogenesis Epidemiology Clinical Manifestations Pediatric Disease Adult Disease Parainfluenza Virus in Immunocompromised Patients Diagnosis Therapy Prevention Key References References Chapter 159 159 Mumps Virus Keywords Short View Summary History Virology Epidemiology Pathogenesis Pathology Clinical Manifestations Complications Immunology Diagnosis Differential Diagnosis Therapy Prevention Key References References Chapter 160 160 Respiratory Syncytial Virus (RSV) Keywords Short View Summary History Description Classification Viral Structure and Characteristics Laboratory Properties Infection in Animals Epidemiology Distribution Seasonal Occurrence Antigenic Variation Epidemiologic Manifestations Prevalence and Incidence Pathogenesis Immunity and Pathogenesis of Disease Innate Immunity Adaptive Immunity Clinical Manifestations Infection among Young Children Otitis Media Infections among Older Children Infections among Adults Complications Patients at High Risk for Severe Infection Immunocompromised Patients Acute Complications in Infants Long-term Complications Diagnosis Therapy Prevention Infection Control Prophylaxis Immunization Key References References Chapter 161 161 Human Metapneumovirus Keywords Short View Summary Virus Pathogenesis and Host Response Epidemiology Clinical Manifestations Children Adults Immunocompromised Hosts Diagnosis Viral Culture Immunofluorescence Assay Reverse-Transcriptase Polymerase Chain Reaction Serology Therapy and Prevention Key References References Chapter 162 162 Measles Virus (Rubeola) Keywords Short View Summary Description of the Pathogen Morphology Chemical and Antigenic Composition Growth of Measles Virus in Tissue Culture Host Range Epidemiology Spread of Infection Other Diseases Associated with Measles Virus Pathogenesis Immunity Clinical Manifestations Complications Special Considerations Modified Measles Atypical Measles Immunocompromised Patients Pregnant Women and Their Offspring Persons with Tuberculosis Occurrence in Adults Diagnosis Prevention Therapy Key References References Chapter 163 163 Zoonotic Paramyxoviruses: Keywords Short View Summary Virology Classification Structure and Molecular Biology Nipah and Hendra Viruses Menangle Virus Emergence of Henipaviruses Nipah Virus Epidemiology Reservoirs and Intermediate Hosts Clinical Manifestations Laboratory Abnormalities Diagnostic Tests Pathology Therapy Prevention Hendra Virus Epidemiology Reservoirs and Intermediate Hosts Clinical Manifestations Laboratory Abnormalities Diagnostic Tests Pathology Therapy Prevention Menangle Virus Epidemiology Pathogenesis Clinical Manifestations and Diagnostic Tests Key References References Chapter 164 164 Vesicular Stomatitis Virus and Related Vesiculoviruses Keywords Short View Summary Classification and Morphology Molecular Biology Epidemiology Epizootic Enzootic Animal Disease Human Disease Diagnosis Host Response and Therapy Prevention and Vaccination Key References References Chapter 165 165 Rabies (Rhabdoviruses) Keywords Short View Summary Virology Classification Composition Replication Strategy Epidemiology Human Rabies Animal Rabies Pathogenesis Pathology Immune Responses Clinical Manifestations Human Rabies Incubation Period Prodromal Symptoms Encephalitic (Furious) Rabies Paralytic (Dumb) Rabies Non-neurologic Findings Animal Rabies Diagnosis Differential Diagnosis Prevention Preexposure Prophylaxis Postexposure Prophylaxis Therapy Key References References Chapter 166 166 Marburg and Ebola Hemorrhagic Fevers (Filoviruses) Keywords Short View Summary Virus Characterization Epidemiology Marburg Hemorrhagic Fever Ebola Hemorrhagic Fever Natural History Clinical Manifestions and Diagnosis Pathogenesis Countermeasures Prevention Treatment Key References References Chapter 167 167 Influenza (Including Avian Influenza and Swine Influenza) Keywords Short View Summary History The Viruses Classification Virology Epidemiology Disease Impact Epidemic Influenza Transmission Pandemic Influenza Antigenic Variation Antigenic Drift Antigenic Shift Emergence of Pandemic Viruses from Birds Human Infections with H7 Viruses Human Infections with H9 Viruses Human Infections with H5 Viruses Factors Controlling Host Range Emergence of Pandemic Viruses from Swine Pathogenesis Cellular Pathogenesis Virus Shedding Histopathology Pathophysiology Host Response Antibody Responses Systemic Antibody Responses Mucosal Antibody Responses Cellular Responses Clinical Manifestations Uncomplicated Influenza Complications of Influenza Pulmonary Complications Primary Influenza Viral Pneumonia Secondary Bacterial Pneumonia Pulmonary Complications in Immunosuppressed Patients Other Pulmonary Complications Nonpulmonary Complications Myositis Cardiac Complications Toxic Shock Syndrome Central Nervous Complications Reye Syndrome Diagnosis Clinical Diagnosis Rapid Influenza Diagnostic Tests Molecular Diagnostic Tests Serology Virus Isolation Role of Viral Diagnosis in Clinical Decision Making Therapy M2 Inhibitors: Amantadine and Rimantadine Mechanism of Action and Activity Pharmacology and Side Effects Efficacy Drug Resistance Neuraminidase Inhibitors: Zanamivir and Oseltamivir Mechanism of Action and Activity Pharmacology and Side Effects Efficacy Drug Resistance Recommendations for Use of Antiviral Agents Investigational Antiviral Agents Prevention Vaccines Inactivated Influenza Vaccine Safety Immune Response Efficacy and Effectiveness Adjuvants Live-Attenuated Influenza Vaccine Safety Immune Response Efficacy and Effectiveness Comparisons of Inactivated Influenza Vaccine and Live-Attenuated Influenza Vaccine Herd Immunity Recommendations for Vaccine Use Vaccines for Pandemic Influenza Chemoprophylaxis Seasonal Prophylaxis Family Prophylaxis Outbreak Prophylaxis Key References References Chapter 168 168 California Encephalitis, Hantavirus Pulmonary Syndrome, and Bunyavirus Hemorrhagic Fevers Keywords Short View Summary Microbiology Structure, Genetics, and Antigenic Relationships Morphogenesis Epidemiology Basic Ecology and Distribution California Encephalitis Viruses Rift Valley Fever Crimean-Congo Hemorrhagic Fever Hantaviruses Transmission to Humans California Encephalitis Viruses Rift Valley Fever Crimean-Congo Hemorrhagic Fever Hantaviruses Clinical Manifestations California Encephalitis Viruses Rift Valley Fever Crimean-Congo Hemorrhagic Fever Hantaviruses Hemorrhagic Fever with Renal Syndrome Hantavirus Pulmonary Syndrome Diagnosis Prevention and Therapy Other Bunyaviridae of Concern Jamestown Canyon Virus Oropouche Virus Toscana Virus Ngari Virus Severe Fever with Thrombocytopenia Syndrome Virus Heartland Virus Acknowledgment Key References References Chapter 169 169 Lymphocytic Choriomeningitis, Lassa Fever, and the South American Hemorrhagic Fevers (Arenaviruses) Keywords Short View Summary Viral Characterization Epidemiology Lymphocytic Choriomeningitis Lassa Fever Other African Arenaviruses South American Hemorrhagic Fevers Other Old World and New World Group Arenaviruses Pathogenesis Rodents Nonhuman Primates Humans Clinical Manifestations Lymphocytic Choriomeningitis Virus Lassa Fever South American Hemorrhagic Fevers Intrauterine Infection Diagnosis Prevention and Treatment Acknowledgment Key References References Chapter 170 170 Human T-Lymphotropic Virus (HTLV) Keywords Short View Summary Structure and Molecular Organization gag, pro, pol, and env TAX REX Proteins Proteins Encoded by the pX Region Biology Laboratory Detection Virus Isolation Serologic Assays and Antigen Detection Nucleic Acid Detection Serologic Epidemiology Geographic Distribution Demographic Patterns Molecular Epidemiology HTLV-1 HTLV-2 HTLV-3 and HTLV-4 Routes of Transmission Mother-to-Child Transmission Sexual Transmission Parenteral Transmission Immunology of HTLV Infection Humoral Immune Responses Cellular Immunity Clinical Manifestations of HTLV Infections HTLV-1–Associated Malignancies HTLV-Associated Myelopathy Other Diseases Associated with HTLV-1 Diseases Associated with HTLV-2 Therapy Asymptomatic HTLV-1 and HTLV-2 Carriers Adult T-Cell Leukemia HTLV-1–Associated Myelopathy and Tropical Spastic Paraparesis Prevention Conclusion Acknowledgments Key References References Chapter 171 171 Human Immunodeficiency Viruses Keywords Short View Summary Origin and Classification of Human Retroviruses Viral Transmission and Life Cycle Biology of Transmission Life Cycle The Pathogen Genetic Organization Virion Structural Proteins Gag Proteins Viral Enzymes pol Gene Products Protease Reverse Transcriptase Integrase Envelope Glycoproteins and Viral Fusion Virus-Cell Fusion Viral Regulatory and Accessory Genes Virus Regulation and the Long Terminal Repeat Virus-Host Interactions Viral Receptors, Chemokines, Receptors, and Tropism Pathogenesis, T-Cell Depletion, and Viral Load Viral Variation: Genetic and Phenotypic Variation Malignancies and Human Immunodeficiency Virus Conclusion Acknowledgment Key References References Chapter 172 172 Introduction to the Human Enteroviruses and Parechoviruses Keywords Enteroviruses Virology Physical Characteristics Molecular Biology Pathogenesis and Immunity in Enteroviral Infections Pathogenesis Viral Mutation during Natural Infection Immunity and the Immune Response Epidemiology of Enteroviral Infections Age and Socioeconomic Status Molecular Epidemiology Transmission Incidence of Infection and Illness Incubation Period and Period of Communicability Laboratory Diagnosis of Enteroviral Infections Viral Isolation Nucleic Acid Amplification and Genomic Sequencing Serology Treatment and Prevention of Enteroviral Infections Parechoviruses Virology Virus Types Viral Diagnosis Epidemiology Key References References Chapter 173 173 Poliovirus Keywords Short View Summary History Pathophysiology Virology Pathogenesis Clinical Manifestations Incubation Period Clinical Manifestations of Infection Spinal Paralytic Poliomyelitis Bulbar Paralytic Poliomyelitis Polioencephalitis Complications Risk Factors Differential Diagnosis Laboratory Diagnosis Prognosis Therapy Postpoliomyelitis Syndrome Poliovirus Immunization Poliovirus Vaccines Inactivated Poliovirus Vaccine Live-Attenuated Poliovirus Vaccine Monovalent and Bivalent Oral Poliovirus Vaccines Vaccine-Associated Paralytic Poliomyelitis Use of Poliomyelitis Vaccines in the Developing World Poliomyelitis in Developing Nations and Global Eradication Vaccine-Derived Poliomyelitis Viruses Key References References Chapter 174 174 Coxsackieviruses, Echoviruses, and Numbered Enteroviruses Keywords Short View Summary Central Nervous System Infections Acute Viral Meningitis Clinical Manifestations Laboratory Diagnosis Differential Diagnosis Management and Prognosis Encephalitis Acute Flaccid Paralysis and Other Neurologic Complications Exanthems Rubelliform and Morbilliform Exanthems Roseoliform Exanthems Herpetiform Exanthems Hand-Foot-and-Mouth Disease Petechial Exanthems and Other Cutaneous Manifestations Acute Respiratory Disease Herpangina Clinical Manifestations Differential Diagnosis Myositis Pleurodynia Epidemiology Pathogenesis Clinical Manifestations Diagnosis Management and Prognosis Other Skeletal Myositis Myopericarditis Etiology and Pathogenesis Clinical Manifestations Diagnostic Virology Management Course and Prognosis Dilated Cardiomyopathy Coxsackievirus and Echovirus Disease in the Newborn Epidemiology Pathophysiology Clinical Manifestations Myocarditis Hepatitis Pneumonia Diagnosis and Differential Diagnosis Management Chronic Meningoencephalitis in Agammaglobulinemic and Other Immunocompromised Patients Clinical Manifestations Prophylaxis and Therapy Infections in Other Immunocompromised Patients Acute Hemorrhagic Conjunctivitis Epidemiology Patterns of Transmission Clinical Manifestations Complications Differential Diagnosis Laboratory Diagnosis Treatment and Prevention Illnesses in Which the Etiologic Role of Enteroviruses Is Minor or Poorly Defined Gastrointestinal Diseases Other Diseases Diabetes Mellitus Enterovirus A71 Infections Key References References Chapter 175 175 Human Parechoviruses Keywords Short View Summary Historical Background Virology Epidemiology Clinical Manifestations Undifferentiated Febrile Illness/Sepsis Syndrome Central Nervous System Infections Meningitis Encephalitis Acute Flaccid Paralysis Gastrointestinal Disease Hemorrhage-Hepatitis Syndrome Necrotizing Enterocolitis Acute Gastroenteritis Respiratory Disease Miscellaneous Clinical Associations Diagnosis Therapy and Prevention Key References References Chapter 176 176 Hepatitis A Virus Keywords Short View Summary History Classification and Physicochemical and Biologic Properties of Hepatitis a Virus Structure Resistance to Physical and Chemical Agents Genome and Proteins Antigenic Composition and Viral Diversity Biology of Hepatitis A Virus in Cell Culture Host Range Epidemiology Modes of Transmission Person to Person Foodborne and Waterborne Bloodborne Vertical Worldwide Disease Patterns Epidemiology in the United States Prevaccine Era Vaccine Era Variation by Age, Race or Ethnicity, and Region Potential Sources of Infection Specific Groups and Settings Child Care Centers, Schools, and Institutions Users of Illicit Drugs Men Who Have Sex with Men Transfusions and Other Health Care Settings International Travel Foodborne and Waterborne Pathogenesis Incubation Period Site of Viral Replication Pathology Clinical Manifestations Symptoms Complications Therapy and General Management Laboratory Diagnosis Immunity Prevention Passive Immunization Active Immunization Recommendations for Prevention Postexposure Prophylaxis Preexposure Prophylaxis Disease Control Strategies Routine Vaccination of Children Vaccination of Persons at Increased Risk of Hepatitis A Infection or Severe Consequences Men Who Have Sex with Men Users of Illicit Drugs International Travelers Close Contacts of Newly Arriving International Adoptees Recipients of Blood or Plasma-Derived Products Persons with Chronic Liver Disease Other Groups and Settings Hepatitis A Vaccination during Outbreaks Directions for the Future Key References References Chapter 177 177 Rhinovirus Keywords Short View Summary Virology Classification Morphology and Structure Replication Host Range Inactivation by Physical and Chemical Agents Epidemiology Geographic Distribution and Prevalence Seasonality Transmission Pathogenesis in Humans Immune Response and Protection from Infection Clinical Manifestations Complications Acute Bacterial Sinusitis Acute Bacterial Otitis Media Exacerbations of Chronic Bronchitis Asthma Other Lower Respiratory Syndromes Infections in Immunocompromised Patients Diagnosis Laboratory Diagnosis Virus Isolation Antigen Detection Nucleic Acid Detection Serologic Assays Prevention and Therapy Vaccines Interferon Blockade of ICAM-1 Receptor Capsid-Binding Agents 3C Protease Inhibitors Virucidal Treatments Key References References Chapter 178 178 Noroviruses and Sapoviruses (Caliciviruses) Keywords Short View Summary History Virology Epidemiology Pathogenesis Immune Response Clinical Manifestations Diagnosis Therapy and Prevention Key References References Chapter 179 179 Astroviruses and Picobirnaviruses Keywords Short View Summary Astroviruses Virology Epidemiology Pathogenesis Clinical Manifestations Diagnosis, Therapy, and Prevention Picobirnaviruses Key References References Chapter 180 180 Hepatitis E Virus Keywords Short View Summary History Virus Molecular Virology Classification Geographic Distribution and Genetic Variation Antigenic Composition Epidemiology Developing Countries Developed Countries Modes of Transmission Host Range: Experimental Transmission to Animals Hepatitis E Virus Infection in Animals Pathogenesis Incubation Period Viral Replication Pathology Immune Response Clinical Manifestations Acute Infection Chronic Infection Solid-Organ Transplant Recipients Coinfection with HIV Complications Extrahepatic Manifestations of Hepatitis E Virus Neurologic Complications Other Complications Associated With Hepatitis E Virus Laboratory Diagnosis Serologic Tests Molecular Tests Immunity Prevention General Sanitation Immunoprophylaxis Therapy Acute Hepatitis E Virus Chronic Hepatitis E Virus Acknowledgment Key References References Chapter 181 181 Prions and Prion Diseases of the Central Nervous System (Transmissible Neurodegenerative Diseases) Keywords Short View Summary Molecular Biology of Prion Diseases Prion Protein Infectious Prions Yeast Prions Human Prion Diseases Sporadic Creutzfeldt-Jakob Disease Genetic Creutzfeldt-Jakob Diseases Gerstmann-Straüssler-Scheinker Syndrome Fatal Familial Insomnia Long-Duration Disease Polymorphisms in PRNP Infectiously Transmitted Human Prion Disease Kuru Variant Creutzfeldt-Jakob Disease Iatrogenic Creutzfeldt-Jakob Disease Prion Disease in Ruminants Laboratory Diagnosis of Prion Disease Prion Disease Therapy Key References References Chapter 182 182 Chlamydia trachomatis (Trachoma, Genital Infections, Perinatal Infections, and Lymphogranuloma Venereum) Keywords Short View Summary Chlamydial Biology Antigenic and Genetic Diversity Pathogenesis Immunity Laboratory Diagnosis Nucleic Acid Amplification Tests Antigen Detection and Nucleic Acid Hybridization Isolation in Cell Culture Cytologic Diagnosis Rapid Tests Serology Clinical Manifestations Trachoma Treatment Oculogenital Disease in Adults Inclusion Conjunctivitis Urogenital Infections Urogenital Infections in Men Urethritis Epididymitis and Prostatitis Proctitis Sexually Reactive Arthritis Urogenital Infections in Women Cervicitis and Urethritis Endometritis and Salpingitis Infertility and Ectopic Pregnancy Pregnancy Complications Other Infections Treatment of Genital and Ocular Infections in Adults Perinatal Infections Neonatal Inclusion Conjunctivitis Infant Pneumonia Prevention and Treatment of Infant Infections Lymphogranuloma Venereum Treatment of Lymphogranuloma Venereum Prevention Strategies Acknowledgment Key References References Chapter 183 183 Psittacosis (Due to Chlamydia psittaci) Keywords Short View Summary Epidemiology Clinical Manifestations and Differential Diagnostic Considerations Laboratory Findings Pathologic Findings Diagnosis Therapy Prevention Key References References Chapter 184 184 Chlamydia pneumoniae Keywords Short View Summary History Microbiology Laboratory Testing for C. Pneumoniae Cell Culture Antigen Detection Nucleic Acid Amplification Tests Serologic Testing Epidemiology Clinical Manifestations Therapy C. pneumoniae and Chronic Disease in Humans C. pneumoniae and Asthma Therapy C. pneumoniae and Other Chronic Diseases C. pneumoniae and Atherosclerosis C. pneumoniae and Multiple Sclerosis Key References References Chapter 185 185 Mycoplasma pneumoniae and Atypical Pneumonia Keywords Short View Summary History Microbiology Epidemiology Immunology and Resistance Innate Immunity Adaptive Immunity Cold Agglutinins Resistance and Susceptibility to Infection Pathology Disease Syndromes Respiratory Illnesses Other Illnesses Dermatologic Syndromes Raynaud’s Phenomenon Cardiac Syndromes Neurologic Syndromes Musculoskeletal, Renal, and Hematologic Syndromes Diagnosis Cold Agglutinins Culture Detection of M. pneumoniae–Specific Antibodies Detection of M. pneumoniae–Specific Antigens Detection of M. pneumoniae–Specific Nucleic Acids Treatment Prevention Infection Control Vaccination Key References References Chapter 186 186 Genital Mycoplasmas: Keywords Short View Summary Taxonomy and Microbiology Epidemiology Clinical Manifestations Ureaplasmas Mycoplasma hominis Mycoplasma genitalium Laboratory Diagnosis Therapy Key References References Chapter 187 187 Introduction to Rickettsioses, Ehrlichioses, and Anaplasmosis Keywords Bacteriology History and Emerging Diseases Pathophysiology Genetics Epidemiology Clinical Findings Diagnosis Treatment Remaining Questions and Perspectives References Chapter 188 188 Rickettsia rickettsii and Other Spotted Fever Group Rickettsiae (Rocky Mountain Spotted Fever and Other Spotted Fevers) Keywords Short View Summary Rocky Mountain Spotted Fever The Pathogen Virulence Factors Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Other Spotted Fever Group Rickettsioses Key References References Chapter 189 189 Rickettsia akari (Rickettsialpox) Keywords Short View Summary Etiology Epidemiology Clinical Manifestations Diagnosis Therapy References Chapter 190 190 Coxiella burnetii (Q Fever) Keywords Short View Summary The Pathogen Epidemiology History Zoonotic Sources Transmission between Humans Incidence Outbreaks Pathogenesis Clinical Manifestations Self-Limited Febrile Illness Pneumonia Clinical Manifestations Radiologic Findings Outcome Laboratory Findings Treatment of Q Fever Pneumonia Diagnosis of Q Fever Pneumonia Follow-up Studies Endocarditis Incidence Clinical Manifestations Diagnosis Treatment of Q Fever Endocarditis Hepatitis Neurologic Manifestations Q Fever in the Immunocompromised Host Other Manifestations of Q Fever Q Fever In Pregnancy Post–Q Fever Fatigue Syndrome Prevention Vaccination Risk Reduction Key References References Chapter 191 191 Rickettsia prowazekii (Epidemic or Louse-Borne Typhus) Keywords Short View Summary Microbiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Key References References Chapter 192 192 Rickettsia typhi (Murine Typhus) Keywords Short View Summary Microbiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Signs and Symptoms Laboratory Features Diagnosis Treatment and Prevention Key References References Chapter 193 193 Orientia tsutsugamushi (Scrub Typhus) Keywords Short View Summary Etiology Epidemiology Clinical Manifestations Diagnosis Therapy Prevention References Chapter 194 194 Ehrlichia chaffeensis (Human Monocytotropic Ehrlichiosis), Anaplasma phagocytophilum (Human Granulocytotropic Anaplasmosis), and Other Anaplasmataceae Keywords Short View Summary Etiology Epidemiology and Epizootiology of Human Monocytotropic Ehrlichiosis Epidemiology and Epizootiology of Human Granulocytic Anaplasmosis Pathogenesis and Pathology Human Monocytotropic Ehrlichiosis Human Granulocytotropic Anaplasmosis Clinical Manifestations Human Monocytotropic Ehrlichiosis Signs and Symptoms Course Diagnosis Differential Diagnosis Ehrlichiosis Caused by Ehrlichia ewingii and Ehrlichia muris Human Granulocytotropic Anaplasmosis Signs, Symptoms, and Course Diagnosis Treatment and Prevention Neoehrlichia Mikurensis Human Infections Prevention of Ehrlichiosis and Anaplasmosis Sennetsu Neorickettsiosis Key References References Chapter 195 195 Introduction to Bacteria and Bacterial Diseases Keywords Classification of Bacteria Variation in Bacterial Infections Polymorphism and Bacterial Infection Bacteria as “New” Causes for “Old” Diseases Bacterial Evolution Bacteria as Therapeutics References Chapter 196 196 Staphylococcus aureus (Including Staphylococcal Toxic Shock Syndrome) Keywords Short View Summary The Microorganism Habitat Culture and Identification Morphology Variants Molecular Diagnosis Molecular Typing Pulsed-Field Gel Electrophoresis Multilocus Sequence Typing Spa Typing and Double-Locus Spa-Clfb Typing Pathogenesis Regulation and Virulence Determinants Regulation agr and Other Two-Component Regulatory Systems DNA-Binding Proteins Small RNAs and Endoribonuclease III Role in Pathogenesis Ecologic and Epidemiologic Implication of agr Cell Surface Determinants Involved in Pathogenesis Biofilm Capsule Surface Adhesins Teichoic Acids and Lipoteichoic Acids Peptidoglycan Secreted Enzymes and Hemolysins Hemolysins Panton-Valentine Leukocidin Exfoliative Toxins and Staphylococcal Scalded Skin Syndrome Molecular Pathogenesis of Staphylococcal Scalded Skin Syndrome Clinical Aspects Superantigens Toxic Shock Syndrome Menstrual Toxic Shock Syndrome Nonmenstrual Toxic Shock Syndrome Predisposing Factors Diagnosis Therapy and Prevention Enterotoxins and Food Poisoning Other Implications of Superantigens Genomics and Mobile Genetic Elements Comparative Genomics and Evolution S. aureus Cross-Species Jump between Humans and Animals Pathogenicity and Genomic Islands Resistance Island Staphylococcal Cassette Chromosome mec Antibiotic Resistance β-Lactams Resistance to Penicillin Methicillin-Resistant S. aureus Health Care–Acquired versus Community-Acquired Methicillin-Resistant S. aureus Mechanism of Methicillin Resistance Glycopeptides Therapeutic Monitoring of Vancomycin in Adult Patients Intermediate Resistance to Glycopeptides Full Resistance to Glycopeptides Daptomycin Protein Synthesis Inhibitors Ribosome Modification Drug Efflux Linezolid Quinolones Mechanisms of Resistance Alternative Treatments Quinupristin-Dalfopristin and Tigecycline β-Lactams with Improved Penicillin-Binding Protein 2A Affinity Lipoglycopeptides Prevention and Prospective Strategies Clinical Aspects and Epidemiology Clinical Spectrum Risk Factors for S. aureus Infection The Burden of Antibiotic Resistance Carriage of S. aureus Carriage of Methicillin-Resistant S. aureus Decolonization of Individual Carriers Clinical Syndromes Skin and Soft Tissues Infections Classification Impetigo Folliculitis Furuncles and Carbuncles Hidradenitis Suppurativa Mastitis Surgical Site Infection Erysipelas, Cellulitis, and Fasciitis Management of Skin and Soft Tissue Infection Bloodstream Infection Community-Onset Bacteremia Nosocomial and Health Care–Associated Bloodstream Infection Management of S. aureus Bloodstream Infection Infective Endocarditis Epidemiology Pathogenesis Role of Bacterial Adhesins Role of Platelets Host Defenses and Prevention Clinical Manifestations Vascular Complications Neurologic Complications Diagnosis Management of S. aureus Endocarditis Management of Right-Sided Endocarditis in Injection Drug Users Meningitis Pericarditis Pulmonary Infections Epidemiology Clinical Spectrum Therapy Osteomyelitis Epidemiology Pathogenesis Clinical Manifestations Prosthetic Joint Infections Diagnosis Therapy Septic Arthritis, Septic Bursitis, and Pyomyositis Septic Arthritis Septic Bursitis Pyomyositis Acknowledgment Key References References Chapter 197 197 Staphylococcus epidermidis and Other Coagulase-Negative Staphylococci Keywords Short View Summary Microbiology and Ecology Antibiotic Resistance Molecular Epidemiology Pathogenesis Virulence Factors Biofilm Adherence Maturation Dispersal Other Virulence Factors Poly-Gamma-dl-Glutamic Acid Antimicrobial Peptide Resistance Lantibiotics Other Coagulase-Negative Species Epidemiology and Clinical Syndromes Colonization and Transmission Bacteremia Intravascular Catheter Infections Endocarditis Cardiac Devices Vascular Grafts Orthopedic Prosthetic Device Infections Cerebrospinal Fluid Shunt Infections Surgical Site Infections Peritoneal Dialysis Catheter-Associated Infections Endophthalmitis Urinary Tract Infection Infections of Genitourinary Prostheses Mastitis and Infections of Breast Implants Miscellaneous Prosthetic Device Infections, Implant Infections, and Other Infections Patient Populations at Increased Risk of Infection by Coagulase-Negative Staphylococci Transplant Patients and Neutropenic Hosts Neonates Burn Patients Non–S. Epidermidis Species of Coagulase-Negative Staphylococci Staphylococcus haemolyticus Staphylococcus lugdunensis Staphylococcus saprophyticus Other Species of Coagulase-Negative Staphylococci Novel Therapeutic Options for Infections Due to Coagulase-Negative Staphylococci Key References References Chapter 198 198 Classification of Streptococci Keywords References Chapter 199 199 Streptococcus pyogenes Keywords Short View Summary History Description of the Pathogen Somatic Constituents Extracellular Products Streptococcal Pharyngitis Epidemiology Clinical Manifestations Scarlet Fever Suppurative Complications Nonsuppurative Complications Diagnosis Throat Culture Rapid Antigen Detection Tests Therapy Streptococcal Pyoderma Epidemiology Bacteriology and Immunology Clinical Manifestations Therapy and Prevention Complications Invasive Streptococcal Infections of Skin and Soft Tissues Erysipelas Streptococcal Cellulitis Necrotizing Fasciitis (Streptococcal Gangrene) Diagnosis and Differential Diagnosis Myositis and Myonecrosis Streptococcal Toxic Shock Syndrome Pathogenesis Mechanisms of Shock and Organ Failure: Cytokine Induction Clinical Manifestations Management Source Control Fluid Resuscitation Antimicrobial Therapy Management in the Intensive Care Unit Dialysis and Hemoperfusion Intravenous Immune Globulin Bacteremia Other Streptococcal Infections Prophylaxis and Risk for Secondary Cases of Streptococcal Toxic Shock Syndrome Key References References Chapter 200 200 Nonsuppurative Poststreptococcal Sequelae: Keywords Short View Summary Rheumatic Fever History Etiology and Pathogenesis Pathologic Findings Epidemiology Clinical Manifestations Diagnosis Therapy and Prognosis Prevention Glomerulonephritis History Etiology and Pathogenesis Pathologic Characteristics Epidemiology Clinical and Laboratory Features Diagnosis Therapy Prevention Prognosis Key References References Additional Reading Chapter 201 201 Streptococcus pneumoniae Keywords Short View Summary History Microbiology Epidemiology Pathogenetic Mechanisms Colonization Pneumococcal Capsular Serotypes and Progression from Colonization to Disease Immunologic Mechanisms of Defense against and Susceptibility to the Pneumococcus Factors That Predispose to Pneumococcal Infection HIV Infection Clinical Syndromes Otitis Media Sinusitis Meningitis Acute Exacerbation of Chronic Bronchitis Pneumonia Overview Pathogenesis Predisposing Factors Symptoms and Physical Findings Radiographic Findings General Laboratory Findings Diagnostic Microbiology Complications Other Infectious Syndromes Noninfectious Syndromes Antibiotic Susceptibility Prevalence of Resistance Therapy Otitis Media Sinusitis Pneumonia Outpatient Therapy Inpatient Therapy Meningitis Miscellaneous Prevention Antibody Responses to Pneumococcal Capsular Polysaccharides Pneumococcal Conjugate Vaccine Efficacy in Children Efficacy of 23-Valent Pneumococcal Polysaccharide Vaccine in Adults Impact of Infant Immunization on Adult Disease Vaccine Protection during HIV Infection Vaccine Recommendations Key References References Chapter 202 202 Enterococcus Species, Streptococcus gallolyticus Group, and Leuconostoc Species Keywords Short View Summary Historical Remarks Microbiology and Taxonomy Colonization, Virulence, and Genomics Epidemiology of Enterococcal Infections Clinical Manifestations of Enterococcal Disease Bacteremia and Endocarditis Urinary Tract Infections Meningitis Intra-abdominal and Pelvic Infections Neonatal Infections Skin, Soft Tissue, and Other Infections Therapy and Antimicrobial Resistance Combination of β-Lactam and Aminoglycosides or Cephalosporins Glycopeptides and Lipoglycopeptides Daptomycin Linezolid Tigecycline Quinupristin-Dalfopristin (Q/D) Other Antienterococcal Antimicrobials Streptococcus Gallolyticus (Bovis) Group Leuconostoc Species Key References References Chapter 203 203 Streptococcus agalactiae (Group B Streptococcus) Keywords Short View Summary Historical Perspective Description Classification and Morphologic Characteristics Identification Serologic Typing Epidemiology and Transmission Asymptomatic Colonization Transmission Incidence and Serotype Distribution of Isolates Pathogenetic Mechanisms Adherence Invasion Bacterial Virulence Factors Host Factors Clinical Manifestations Primary Bacteremia Infections of the Female Genital Tract Infections in Infants Pneumonia Endocarditis Arthritis Osteomyelitis Skin and Soft Tissue Infections Meningitis Urinary Tract Infections Uncommon Manifestations of Infection Recurrent Invasive Group B Streptococcal Infection Diagnosis Treatment Prevention Group B Streptococcal Vaccines Key References References Chapter 204 204 Viridans Streptococci, Nutritionally Variant Streptococci, Groups C and G Streptococci, and Other Related Organisms Keywords Short View Summary Viridans Group Streptococci Microbiology Species Identification Epidemiology Pathogenicity Clinical Manifestations and Therapy Endocarditis Bacteremia Meningitis Pneumonia Endophthalmitis Miscellaneous Infections Antimicrobial Resistance and Principles of Therapy Nutritionally Variant (Deficient) Streptococci (Abiotrophia and Granulicatella) β-Hemolytic Streptococci (Groups C And G) Microbiology Group C Streptococci Group G Streptococci Epidemiology Group C Streptococci Group G Streptococci Clinical Manifestations Pharyngitis Complications of Pharyngitis Skin and Soft Tissue Infection Arthritis Osteomyelitis Respiratory Tract Infections Endocarditis Meningitis Puerperal Infection Neonatal Sepsis Bacteremia Miscellaneous Infections Treatment Group C Streptococci Group G Streptococci Streptococcus Iniae Streptococcus Suis Rothia and Pediococcus Key References References Chapter 205 205 Streptococcus anginosus Group Keywords Short View Summary Bacteriologic Characteristics Taxonomy Normal Habitat Pathogenicity Clinical Manifestations Head and Neck Infections Bacteremia and Endocarditis Central Nervous System Infections Abdominal Infections Thoracic Infections Miscellaneous Infections Antimicrobial Therapy Key References References Chapter 206 206 Corynebacterium diphtheriae (Diphtheria) Keywords Short View Summary History Pathogen Epidemiology Pathogenesis Clinical Manifestations Respiratory Tract Diphtheria Anterior Nasal Faucial Laryngeal and Tracheobronchial Cardiac Toxicity Neurologic Toxicity Other Complications Cutaneous Diphtheria Invasive Disease Other Sites Diagnosis Therapy Prevention Key References References Chapter 207 207 Other Coryneform Bacteria and Rhodococci Keywords Short View Summary Coryneform Bacteria Other Than Corynebacterium Diphtheriae Taxonomy Microbiology Nonlipophilic, Fermentative Corynebacteria Corynebacterium ulcerans and Corynebacterium pseudotuberculosis Corynebacterium xerosis Corynebacterium striatum Corynebacterium minutissimum Corynebacterium amycolatum Corynebacterium glucuronolyticum Other Nonlipophilic, Fermentative Corynebacteria Nonlipophilic, Nonfermentative Corynebacteria Corynebacterium afermentans subsp. afermentans Corynebacterium auris Corynebacterium pseudodiphtheriticum Corynebacterium propinquum Lipophilic Corynebacteria Corynebacterium jeikeium Microbiology Pathogenicity Treatment Corynebacterium urealyticum Microbiology Pathogenicity Treatment Other Lipophilic Corynebacteria Arcanobacteria Arcanobacterium haemolyticum Microbiology Infections in Humans Treatment Arcanobacterium (Actinomyces) pyogenes Arcanobacterium bernardiae Miscellaneous Coryneform Bacteria Turicella otitidis Arthrobacter Species Brevibacterium Species Dermabacter hominis Rothia dentocariosa and Rothia mucilaginosa Oerskovia Species Microbacterium Species Leifsonia aquatica Rhodococci Rhodococcus equi Other Rhodococcus Species and Related Genera Key References References Chapter 208 208 Listeria monocytogenes Keywords Short View Summary Microbiology Epidemiology Pathogenesis Immunity Clinical Syndromes Infection in Pregnancy Neonatal Infection Bacteremia Central Nervous System Infection Meningitis Encephalitis (Cerebritis) Brainstem Encephalitis (Rhombencephalitis) Brain Abscess Spinal Cord Infection Endocarditis Localized Infection Febrile Gastroenteritis Complications Diagnosis Treatment Prevention Key References References Additional Reading Chapter 209 209 Bacillus anthracis (Anthrax) Keywords Short View Summary Epidemiology Microbiology Clinical Manifestations and Diagnosis Cutaneous Anthrax Injection Anthrax Inhalational or Pulmonary Anthrax Gastrointestinal Anthrax Anthrax Meningitis Therapy Cutaneous Anthrax Inhalational, Gastrointestinal, and Meningeal Anthrax Management of Pleural Effusion and Ascites Role of Corticosteroids and Management of Severe Edema Anthrax Immunotherapeutics Prevention Anthrax as an Agent of Bioterrorism History of Bacillus anthracis as a Bioterrorist Agent Dissemination of Anthrax as a Bioterrorist Agent Outbreak Characteristics after Use of Anthrax as a Bioterrorist Agent Anthrax Countermeasures Diagnostics Antibiotics Vaccines Immunotherapy Infection Control Remediation (Decontamination) Key References References Chapter 210 210 Bacillus Species and Related Genera Other Than Bacillus anthracis Keywords Short View Summary Microbiology Epidemiology Pseudoinfection and Contamination Commercial Uses of Bacillus Species Adherence Properties Clinical Manifestations Food Poisoning Systemic Infections Central Nervous System Infections Respiratory Infections Eye Infections Soft Tissue, Skin, and Muscle Infection Prevention Therapy Key References References Chapter 211 211 Erysipelothrix rhusiopathiae Keywords Short View Summary Microbiology Epidemiology Pathogenesis Clinical Manifestations Therapy and Prevention Key References References Chapter 212 212 Whipple’s Disease Keywords Short View Summary Etiology Epidemiology and Pathogenesis Pathology Clinical Features and Diagnosis Therapy and Prognosis References Chapter 213 213 Neisseria meningitidis Keywords Short View Summary Definition and History Microbiology Biology and Pathogenesis Meningococcal Colonization and Transmission Host Susceptibility Epidemiology Clinical Manifestations and Pathophysiology Meningococcemia Meningitis Rash of Meningococcal Disease Complement Deficiency and Meningococcal Disease Chronic Meningococcemia Primary (Purulent) Pericarditis Septic Arthritis Respiratory Tract Infections Conjunctivitis Meningococcal Urethritis and Proctitis Complications Family and Community Impact Diagnosis Treatment Antibiotic Therapy Adjunct Therapy and Supportive Care Prevention Chemoprophylaxis Immunoprophylaxis Immune Correlates of Protection and Meningococcal Polysaccharide Vaccines Meningococcal Conjugate Vaccines Serogroup B Vaccine Strategies Duration of Protection Immunologic Memory and Interference Population Coverage and Effectiveness Herd Immunity and Introduction Strategies Meningococcal Vaccine Recommendations Adolescents and Adults Infants and Children Postexposure Immunoprophylaxis Hajj Pilgrimage Future Meningococcal Disease Vaccine Prevention Strategies Key References References Chapter 214 214 Neisseria gonorrhoeae (Gonorrhea) Keywords Short View Summary The Organism Description Growth and Cultivation Surface Structures Type IV Pili Outer Membrane Strain Typing Genetics Plasmids Chromosomal Mutations and Transformation Pathobiology of Gonococcal Infection Infection of the Male Urethra Infection of the Lower Female Genital Tract Infection of the Upper Female Genital Tract Epidemiology Incidence Transmission Antimicrobial Resistance Clinical Manifestations Genital Infection in Men Uncomplicated Infection Localized Complications Uncomplicated Urogenital Infection in Women Rectal Gonococcal Infection Pharyngeal Infection Other Local Manifestations Pelvic Inflammatory Disease Perihepatitis Gonorrhea in Pregnancy Disseminated Gonococcal Infection Neonatal and Pediatric Infections Diagnosis Culture Nucleic Acid Amplification Tests Gram-Stained Smears Other Diagnostic Methods Therapy Uncomplicated Gonorrhea in Adults Initial Single-Dose Treatment Co-treatment for Chlamydial Infection Follow-Up of Patients Treated for Uncomplicated Gonorrhea Pelvic Inflammatory Disease Acute Epididymitis Disseminated Gonococcal Infection Gonorrhea in Children Management of Sex Partners Prevention and Control Public Health Strategies Condoms and Microbicides Other Prevention Strategies Key References References Chapter 215 215 Moraxella catarrhalis, Kingella, and Other Gram-Negative Cocci Keywords Short View Summary Moraxella Catarrhalis History Microbiology Epidemiology and Respiratory Tract Colonization Pathogenesis Clinical Manifestations Otitis Media Lower Respiratory Tract Infections in Chronic Obstructive Pulmonary Disease Pneumonia in Older Adults Nosocomial Respiratory Tract Infections Sinusitis Bacteremia Therapy Other Neisseria Other Moraxella Kingella History and Microbiology Epidemiology and Respiratory Tract Colonization Clinical Manifestations Skeletal Infections Endocarditis Bacteremia Other Infections Therapy Key References References Chapter 216 216 Vibrio cholerae Keywords Short View Summary Classification and Genomics Pathogenicity Epidemiology Clinical Manifestations Diagnosis Treatment Immune Responses Prevention and Vaccines Key References References Chapter 217 217 Other Pathogenic Vibrios Keywords Short View Summary Vibrio Parahaemolyticus Epidemiology Clinical Manifestations Laboratory Findings Differential Diagnosis Therapy Prevention Vibrio Vulnificus Clinical Manifestations Differential Diagnosis Therapy Prevention Vibrio Alginolyticus Halophilic Vibrios Nonhalophilic Vibrios: Non-O1/O139 Vibrio Cholerae and Vibrio Mimicus Epidemiology Clinical Manifestations Laboratory Findings Therapy Prevention Key References References Chapter 218 218 Campylobacter jejuni and Related Species Keywords Short View Summary Etiology Epidemiology Pathogenesis and Pathologic Characteristics Immunity Clinical Manifestations Campylobacter jejuni Infections Campylobacter fetus Infections Infection Caused By Other Enteric Campylobacter Species Diagnosis Direct Examination of Feces Bacteriologic Studies Therapy Antibiotic Resistance Resistance to Fluoroquinolones Resistance to Macrolides Prognosis Key References References Chapter 219 219 Helicobacter pylori and Other Gastric Helicobacter Species Keywords Short View Summary Microbiology Epidemiology Pathology and Pathogenesis Clinical Consequences Associated with H. pylori Colonization Acute Acquisition Persistent Colonization Duodenal Ulceration Gastric Ulceration Gastric Carcinoma Gastric Lymphoma Esophageal Diseases Asthma and Related Disorders Metabolic Disorders Idiopathic Thrombocytopenic Purpura Overview of Clinical Consequences Diagnosis Therapy Indications Therapies Other Gastric Helicobacters Key References References Chapter 220 220 Enterobacteriaceae Keywords Short View Summary General Properties Epidemiology Structural and Surface Antigenic Features Inner Membrane Periplasmic Space Peptidoglycan Cell Wall Outer Membrane Lipopolysaccharide Capsule and Other Surface Polysaccharides Flagella Pili Virulence and Virulence Factors Adhesins Secretion Systems and Toxins Iron Acquisition Lipopolysaccharide and Capsules Plasmids Specific Organisms Escherichia Extraintestinal Pathogenic E. coli Enterotoxigenic E. coli Enteropathogenic E. coli Enterohemorrhagic E. coli and Other Shiga Toxin–Producing E. coli Strains Enteroaggregative E. coli Enteroinvasive E. coli Other Pathotypes of E. coli and Species of Escherichia Klebsiella Enterobacter, Pantoea, Serratia, Citrobacter, and Hafnia Enterobacter Species and Pantoea (Enterobacter) Agglomerans Serratia Species Citrobacter Species Hafnia alvei Proteus, Providencia, and Morganella Other Genera Key References References Chapter 221 221 Pseudomonas aeruginosa and Other Pseudomonas Species Keywords Short View Summary Microbiology The Pseudomonas aeruginosa Genome P. aeruginosa and the Human Microbiota Virulence Factors Pili Flagella Type I and II Secretion Systems (T1SS and T2SS) Type III Secretion Systems (T3SS) Quorum-Sensing Molecules Other Virulence Factors Epidemiology Transmission Dynamics of Pseudomonas aeruginosa and Reservoirs Antimicrobial Resistance Resistance Mechanisms Intrinsic Resistance Decreased Permeability of the Outer Membrane Efflux Pumps Antimicrobial-Modifying Enzymes Acquired Resistance Aminoglycoside-Modifying Enzyme Bloodstream Infections Infective Endocarditis Pneumonia Pneumonia Associated with Hospital Exposure Hospital-Acquired (Nosocomial) Pneumonia Hospital-Acquired Pneumonia among Ventilated Patients Hospital-Acquired Pneumonia among Nonventilated Patients Health Care–Associated Pneumonia Community-Acquired Pneumonia Chronic Respiratory Tract Infections Bone and Joint Infections Sternoclavicular Septic Arthritis Septic Arthritis of the Symphysis Pubis Vertebral Osteomyelitis Skull Base Osteomyelitis Osteomyelitis Related to Nail Puncture Wounds Combat-Related Osteomyelitis Antimicrobial Therapy for Arthritis and Osteomyelitis Skin and Soft Tissue Infections Paronychia and Green Nail Syndrome Interdigital Infections Hot Tub Folliculitis Hot Hand-Foot Syndrome Body Piercing Ecthyma Gangrenosum Ear Infections Simple Otitis Externa (Swimmer’s Ear) Malignant Otitis Externa (Necrotizing Otitis Externa) Eye Infections Keratitis Endophthalmitis Urinary Tract Infections Pseudomonas Species Other Than P. Aeruginosa of Major Clinical Significance Pseudomonas fluorescens Pseudomonas fulva Pseudomonas luteola Pseudomonas mendocina Pseudomonas mosselii Pseudomonas oryzihabitans Pseudomonas putida Pseudomonas stutzeri Novel Therapeutic Strategies Against P. Aeruginosa Infections Key References References Chapter 222 222 Stenotrophomonas maltophilia and Burkholderia cepacia Keywords Short View Summary Microbiology Burkholderia cepacia Complex Genotypes Stenotrophomonas Genotypes Identification Pathogenesis Bacterial Factors Avoidance of Host Immunity and Tissue Damage Extracellular Enzymes Siderophores Outer Membrane Lipopolysaccharides Damage to Immune Effector Cells Adhesion and Cell Invasion Chronic Infection and Colonization Intracellular Milieu and Survival Biofilm and Quorum Sensing Epidemiology and Susceptible Population Stenotrophomonas maltophilia Population at Risk Burkholderia cepacia Complex Population at Risk Clinical Manifestations Stenotrophomonas maltophilia Catheter-Related S. maltophilia Bacteremia Non–Catheter-Related Bacteremia Endovascular Infection Pulmonary Infection Skin and Skin Structure Infection Central Nervous System Infection Paranasal and Mastoid Sinus Infections Eye Infections Genitourinary Tract Infection Abdominopelvic Infection Bone and Joint Infections Burkholderia cepacia Complex Respiratory Tract Infection in Cystic Fibrosis Lung Transplantation Hemophagocytic Syndrome Bacteremia and Pneumonia Skin, Skin Structure, and Joint Infection Genitourinary Tract Infection Therapy Stenotrophomonas maltophilia Antimicrobial Resistance and Drug Therapy Burkholderia cepacia Complex Antimicrobial Resistance and Drug Therapy Multidrug-Resistant Bacteria Prevention Immunization Immunotherapy Key References References Chapter 223 223 Burkholderia pseudomallei and Burkholderia mallei: Keywords Short View Summary Melioidosis History Etiology Epidemiology Transmission Pathogenesis Clinical Manifestations Laboratory Diagnosis Therapy Initial Intensive Therapy Subsequent Eradication Therapy Adjunctive Therapy Prevention Glanders History Etiology Epidemiology, Transmission, and Pathogenesis Clinical Manifestations Laboratory Diagnosis Therapy Prevention Key References References Chapter 224 224 Acinetobacter Species Keywords Short View Summary Epidemiology Health Care–Associated Infections Community-Associated Infections Trauma Diagnosis Clinical Manifestations Pathogenesis and Antimicrobial Resistance Therapy β-Lactam Antibiotics β-Lactamase Inhibitors Aminoglycosides Tigecycline and Minocycline Polymyxins Combination Treatment Prevention Key References References Chapter 225 225 Salmonella Species Keywords Short View Summary Classification and Taxonomy The Genome Microbiology Epidemiology Nontyphoidal Salmonellae Pathogenesis Interactions with Intestinal Epithelium and Induction of Enteritis Interactions with Macrophages and Systemic Infection Host Response and Immunity Clinical Manifestations Gastroenteritis Enteric Fever Bacteremia and Vascular Infection Salmonellosis and HIV Infection Localized Infections Chronic Carrier State Immunization Against Salmonella Therapy for Salmonellosis Enteric (Typhoid) Fever Nontyphoidal Salmonella Bacteremia Recurrent Salmonella Bacteremia in Persons with Human Immunodeficiency Virus Focal Infections Carrier State Prevention and Control Key References References Chapter 226 226 Bacillary Dysentery: Shigella and Enteroinvasive Escherichia coli Keywords Short View Summary Microbiology Isolation Techniques Group and Type Identification Invasive Escherichia coli Pathogenesis Communicability and Infectivity Mucosal Invasion and Inflammation Toxigenicity Anatomic Location of Infection Epidemiology Cyclic Patterns of Disease Incidence of Shigellosis by Geography and Host Modes of Spread and Reservoirs in Nature Diagnosis History Physical Examination Laboratory Findings Therapy and Clinical Course Control Environmental Control Immunologic Control Key References References Chapter 227 227 Haemophilus Species, Including H. influenzae and H. ducreyi (Chancroid) Keywords Short View Summary Haemophilus Influenzae Description of the Pathogen Distinguishing H. influenzae from H. haemolyticus Biotypes Serotypes Epidemiology and Respiratory Tract Colonization Colonization in Children Colonization in Adults with Chronic Obstructive Pulmonary Disease Colonization and Conjugate Vaccines Pathogenesis Otitis Media Otitis Media with Effusion Biofilms Exacerbations of Chronic Obstructive Pulmonary Disease Invasive Infections Caused by Haemophilus influenzae Type b Immunity Nontypeable Haemophilus influenzae Haemophilus influenzae Type b Clinical Manifestations of Nontypeable Haemophilus influenzae Otitis Media Exacerbations of Chronic Obstructive Pulmonary Disease Community-Acquired Pneumonia Acute Respiratory Tract Infections in Children in Developing Countries Sinusitis Neonatal and Maternal Sepsis Bacteremia and Invasive Infections Conjunctivitis Clinical Manifestations of Haemophilus influenzae Type b Meningitis Epiglottitis Pneumonia and Empyema Cellulitis Bacteremia without Localized Disease Septic Arthritis Diagnosis Nontypeable Haemophilus influenzae Haemophilus influenzae Type b Therapy Nontypeable Haemophilus influenzae Haemophilus influenzae Type b Chemoprophylaxis for Haemophilus influenzae Type b Active Immunization against Haemophilus influenzae Type b Haemophilus influenzae Biogroup aegyptius Haemophilus Ducreyi Description of the Pathogen Epidemiology Pathogenesis and Immune Response Clinical Manifestations Diagnosis Therapy Other Haemophilus Species Description of the Pathogen Clinical Manifestations Therapy Key References References Chapter 228 228 Brucellosis (Brucella Species) Keywords Short View Summary History Microbiology Epidemiology Pathogenesis Immune Response Clinical Manifestations Complications Skeletal System Nervous System Genitourinary Tract Cardiovascular System Gastrointestinal System Hepatobiliary System Respiratory System Hematologic Complications Cutaneous Lesions Ocular Lesions Pregnancy Diagnosis Treatment Prevention Key References References Chapter 229 229 Francisella tularensis (Tularemia) Keywords Short View Summary History Microbiology Virulence Other Francisella Species Epidemiology Distribution Incidence Transmission Pathogenesis Immunity Clinical Manifestations Ulceroglandular and Glandular Tularemia Oculoglandular Tularemia Pharyngeal Tularemia Typhoidal Tularemia Pneumonic Tularemia Secondary Skin Manifestations F. tularensis subsp. novicida and F. philomiragia Infections Clinical Recognition of a Bioterrorism Event Complications and Outcome Diagnosis Routine Cultures and Pathology Rapid Diagnostic Tests Serologic Diagnosis Investigational Diagnostic Assays Therapy Antibiotic Treatment Pregnant and Immunosuppressed Patients Surgical Treatment Immunotherapy Therapy for Tularemia after a Bioterrorism Event Prevention Vaccination Antibiotic Prophylaxis Antibiotic Prophylaxis after a Tularemia Bioterrorism Event Key References References Chapter 230 230 Pasteurella Species Keywords Short View Summary Description of the Pathogen Epidemiology Pathogenesis Clinical Manifestations Skin and Soft Tissue Infections Bone and Joint Infections Central Nervous System Infections Bacteremia and Endocarditis Respiratory Tract Infections Intra-abdominal Infections Other Pasteurella Infections Therapy, Prevention, and Prognosis Key References References Chapter 231 231 Yersinia Species (Including Plague) Keywords Short View Summary Yersinia Pestis History Microbiology Epidemiology Natural Cycles Transmission to Humans Pathogenesis Clinical Manifestations Bubonic Plague Septicemic Plague Pneumonic Plague Other Syndromes Laboratory Findings Diagnosis Therapy Antimicrobial Agents Supportive Therapy Prevention Infection Control Chemoprophylaxis Vaccination Environmental Control Bioterrorism Mass Prophylaxis Occupational Exposure Environmental Persistence Yersinia Enterocolitica and Yersinia Pseudotuberculosis History Microbiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Therapy Prevention Acknowledgments Key References References Chapter 232 232 Bordetella pertussis Keywords Short View Summary History Description of Pathogen Pathogenesis Epidemiology Prevaccine Era Vaccine Era Current Issues Regarding Resurgence of Pertussis Carrier State Clinical Presentation Young Children Infants and Adults Complications Diagnosis Culture Molecular Diagnosis Serology Direct Fluorescent Antibody Therapy Antimicrobial Agents Supportive Care Prevention Immunization Whole-Cell Vaccines Acellular Pertussis Vaccines Vaccination Schedules Vaccination of Health Care Workers Protection of Infants Chemoprophylaxis Pertussis in Schools and Daycare Centers Future Directions Key References References Chapter 233 233 Rat-Bite Fever: Keywords Short View Summary Streptobacillus Moniliformis Bacteriology Epidemiology Clinical Manifestations Diagnosis Therapy and Prevention Spirillum Minus Bacteriology Epidemiology, Pathogenesis, and Pathology Clinical Manifestations Diagnosis and Therapy Key References References Chapter 234 234 Legionnaires’ Disease and Pontiac Fever Keywords Short View Summary Introduction and History Etiologic Agent Microbial Ecology Pathogenesis Overview L. pneumophila Virulence Factors Virulence Factors and Pathogenesis of Other Legionella spp. Epidemiology Incubation Period and Contagiousness Patterns and Rates of Disease and Mortality Risk Factors Modes of Transmission Outbreak Investigation Environmental Decontamination for Outbreaks Clinical Manifestations Legionnaires’ Disease Extrapulmonary Infections Pontiac Fever Laboratory Diagnosis Therapy and Response to Therapy Prevention Immunization and Chemoprophylaxis Engineering Modifications and Maintenance Environmental Cultures for Legionella Bacteria Key References References Chapter 235 235 Capnocytophaga Keywords Short View Summary Taxonomy Pathogenesis and Clinical Manifestations Human Oral-Associated Species Infections Associated with Zoonotic Species Epidemiology Diagnosis and Laboratory Identification Therapy Prevention Key References References Chapter 236 236 Bartonella, Including Cat-Scratch Disease Keywords Short View Summary Background and Classification Epidemiology of the Common Human-Pathogenic Species Clinical Manifestations of the Common Human-Pathogenic Species Oroya Fever and Verruga Peruana: Bartonella bacilliformis Bacteremic Illness and Endocarditis: Bartonella quintana, Bartonella henselae, and Other Bartonella Species Other Species Bacillary Angiomatosis/Peliosis: Bartonella quintana and Bartonella henselae Cat-Scratch Disease: Bartonella henselae Background Typical Cat-Scratch Disease Musculoskeletal Manifestations Atypical Manifestations Encephalopathy Ocular Manifestations Differential Diagnosis HIV-Associated Neurologic Syndromes Bartonella henselae Infections in Solid Organ Transplant Recipients Pathogenesis Laboratory Diagnosis Direct Examination Specimen Collection and Handling for Culture Culture Identification Antimicrobial Susceptibility Testing Molecular Methods Serologic Testing Therapy and Prevention Endocarditis and Bacteremia Cat-Scratch Disease Neuroretinitis and Neurologic Disease Prevention Key References References Chapter 237 237 Klebsiella granulomatis (Donovanosis, Granuloma Inguinale) Keywords Short View Summary Biology of the Causative Organism Geographic Distribution and Epidemiology Clinical Manifestations Diagnosis Therapy Key References References Chapter 238 238 Other Gram-Negative and Gram-Variable Bacilli Keywords Short View Summary Glucose Fermenters Actinobacillus and Aggregatibacter Species Aeromonas Species Cardiobacterium Species Chromobacterium Species Dysgonomonas Species Centers for Disease Control and Prevention Group EF-4 Plesiomonas Species Glucose Nonfermenters or Weak Fermenters Achromobacter and Alcaligenes Species Chryseobacterium and Elizabethkingia Species Comamonas and Delftia Species Eikenella Species Flavobacterium and Myroides Species Ochrobactrum Species Oligella Species Pseudomonas Species Ralstonia and Cupriavidus Species Rhizobium (Formerly Agrobacterium) Species Roseomonas Species and Other “Pink-Pigmented” Gram-Negative Bacilli Shewanella Species Sphingobacterium Species Sphingomonas Species Weeksella and Bergeyella Species Centers for Disease Control and Prevention Groups Gardnerella and Mobiluncus Species Key References References Chapter 239 239 Syphilis (Treponema pallidum) Keywords Short View Summary History Etiology Epidemiology Pathogenesis Pathologic Features Natural Course of Untreated Syphilis Clinical Manifestations Primary Syphilis Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis Asymptomatic Neurosyphilis Syphilitic Meningitis Meningovascular Syphilis Parenchymatous Syndromes Central Nervous System Gumma Ocular Syphilis Otosyphilis Cardiovascular Syphilis Late Benign (Gummatous) Syphilis Laboratory Diagnosis Direct Examination for Spirochetes Darkfield Microscopy and DFA-TP Visualization of Treponema pallidum in Tissues Polymerase Chain Reaction Detection of T. pallidum Serologic Tests Nontreponemal Tests Treponemal Tests Syphilis Serologic Tests in HIV Infection Rapid Point-of-Care Tests Tests for Neurosyphilis Therapy Principles of Syphilotherapy Early Syphilis Latency Tertiary Syphilis Cardiovascular and Gummatous Syphilis Neurosyphilis Penicillin Allergy Gestational Syphilis Jarisch-Herxheimer Reaction Congenital Syphilis Immunity Acknowledgments Key References References Chapter 240 240 Endemic Treponematoses Keywords Short View Summary The Organisms Epidemiology Clinical Manifestations Yaws Endemic Syphilis (Bejel) Pinta Diagnosis Therapy Public Health Management and Control Strategies Key References References Chapter 241 241 Leptospira Species (Leptospirosis) Keywords Short View Summary History Etiology Epidemiology and Transmission Pathogenesis Clinical Manifestations Laboratory Diagnosis Direct Detection Methods Isolation and Identification Indirect Detection Methods Therapy Prevention Key References References Chapter 242 242 Relapsing Fever Caused by Borrelia Species Keywords Short View Summary Organism Epidemiology and Transmission Pathophysiology Clinical Manifestations Diagnosis Therapy Prevention Key References References Chapter 243 243 Lyme Disease (Lyme Borreliosis) Due to Borrelia burgdorferi Keywords Short View Summary Causative Organism Vector of Transmission and Animal Hosts Epidemiology Pathogenesis Clinical Characteristics Early Infection: Stage 1 (Localized Infection) Early Infection: Stage 2 (Disseminated Infection) Late Infection: Stage 3 (Persistent Infection) Post–Lyme Disease Symptoms or Syndrome Congenital Infection Coinfection Laboratory Diagnosis Differential Diagnosis Therapy Prevention Key References References Chapter 244 244 Anaerobic Infections: Keywords Definition of an Anaerobe Anaerobes in the Normal Human Microbiota Etiology of Anaerobic Clinical Infections Clinical Syndromes Caused by Anaerobes Anaerobic Infections of the Mouth, Head, and Neck Pleuropulmonary Infections Intra-abdominal Infections Pelvic Infections Central Nervous System Infections Skin and Soft Tissue Infections Bone and Joint Infections Anaerobic Bacteremia Pathogenesis of Anaerobic Infections Diagnosis of Anaerobic Infections Treatment of Anaerobic Infections and Antibiotic Resistance Acknowledgment Key References References Chapter 245 245 Clostridium difficile Infection Keywords Short View Summary Historical Overview Pathogenesis The Indigenous Gut Microbiota and Antibiotics Sporulation and Germination in Clostridium difficile Toxin Production Other Virulence Factors Host Response to Clostridium difficile Infection Pathogenesis of Recurrent Clostridium difficile Infection Altered Virulence in Specific Clostridium difficile Lineages Epidemiology Health Care–Associated Clostridium difficile Infection Community-Associated Clostridium difficile Infection Molecular Epidemiology of Clostridium difficile Infection and Importance of Clostridium difficile Strain Type Clostridium difficile Infection in Children Risk Factors Clostridium difficile Infection Recurrent Clostridium difficile Infection Severe Clostridium difficile Infection Infection Control and Prevention Clinical and Pathologic Manifestations Diagnosis Therapy Mild to Moderate Clostridium difficile Infection Severe Clostridium difficile Infection Severe Complicated or Fulminant Clostridium difficile Infection First Recurrence of Clostridium difficile Infection Multiple Recurrences of Clostridium difficile Infection and Fecal Microbiota Transplants Monitoring Outcome of Therapy Conclusion Key References References Chapter 246 246 Tetanus (Clostridium tetani) Keywords Short View Summary History Epidemiology Characteristics of Clostridium Tetani Pathogenesis Clinical Manifestations Diagnosis Therapy Prophylaxis Key References References Chapter 247 247 Botulism (Clostridium botulinum) Keywords Short View Summary History of Botulism Epidemiology Characteristics of Clostridium Botulinum Pathogenesis Clinical Manifestations Diagnosis Therapy Prevention Key References References Chapter 248 248 Gas Gangrene and Other Clostridium-Associated Diseases Keywords Short View Summary Characteristics of Clostridium Spp. Clostridium perfringens and Clostridial Myonecrosis (Gas Gangrene) Pathogenesis Diagnosis and Treatment Food Poisoning Caused by Clostridium perfringens Other Clostridial Infections Bacteremia Abdominal Infections Biliary Tract Infections Female Genital Tract Infections Pleuropulmonary Infections References Chapter 249 249 Bacteroides, Prevotella, Porphyromonas, and Fusobacterium Species (and Other Medically Important Anaerobic Gram-Negative Bacilli) Keywords Short View Summary Overview History Microbiology Bacteroides Prevotella and Porphyromonas Fusobacterium Symbiosis Gastrointestinal Tract Symbiosis and Mutualism in Immunity and Metabolism Female Urogenital Tract Oropharynx Opportunism Endotoxic Lipopolysaccharide Capsular Polysaccharides Pili and Fimbriae Enzymes and Toxins Metabolic End Products Host Immune Response Infections Bacteremia Skeletal Infection Skin and Soft Tissue Infection Central Nervous System Infection Infections of the Aerodigestive Tract Oropharyngeal Infections Salivary Gland Infections Ear Infections Thoracic Infections Cardiovascular Infections Intra-abdominal Infections Peritonitis Enteritis Urogenital Tract Infections Recent Associations of GRAM-NEGATIVE ANAEROBIC RODS and Disease THERAPY Surgical Treatment Antibiotic Therapy References Chapter 250 250 Anaerobic Cocci and Anaerobic Gram-Positive Nonsporulating Bacilli Keywords Taxonomy Members of the Commensal Microbiota Clinical Significance Gram-Positive Anaerobic Cocci Anaerococcus Finegoldia Parvimonas Peptoniphilus Peptostreptococcus Murdochiella Gram-Negative Anaerobic Cocci Acidaminococcus Anaeroglobus Megasphaera Negativicoccus Veillonella Gram-Positive Anaerobic Nonsporulating Rods Propionibacteria Lactobacilli Bifidobacteria Atopobium and Olsenella Actinomyces-Like Organisms Mobiluncus Eggerthella and Related Species Eubacterium and Related Taxa Microbiologic Aspects Treatment Key References References Chapter 251 251 Mycobacterium tuberculosis Keywords Short View Summary History Microbiology Acid-Fast Staining Culture Methods for M. tuberculosis Nucleic Acid Amplification Detection of Mycobacterial Antigens in Urine Speciation of Mycobacteria Genotyping of M. tuberculosis Drug Susceptibility Testing Epidemiology General Considerations Recent Morbidity and Mortality Trends Drug-Resistant Tuberculosis Mode of Spread Risk for Infection Influence of Chemotherapy on Spread of Infection Risk for Progression from Infection to Active Disease Institutional Spread of Tuberculosis Hospitals Shelters for the Homeless Correctional Facilities Controlling Nosocomial Spread Immunology Tuberculin Skin Test Dosage Technical Aspects Targeted Tuberculin Testing Interpretation Booster Effect False-Positive and False-Negative Reactions Variant (“Delayed”) Tuberculin Reactivity Loss of Tuberculin Reactivity Tuberculin Skin Testing and HIV Infection Interferon-γ Release Assays for Latent M. tuberculosis Infection Pathogenesis Evolution of the Primary Infection Primary (Childhood) and Reinfection (Adult) Tuberculosis Chronic Pulmonary Tuberculosis Apical Localization Endogenous versus Exogenous Reinfection Influence of Age on Tuberculous Infection Infection in Infancy and Childhood Infection in Adolescence and Young Adulthood Infection in Midadulthood Infection in Old Age Late Hematogenous Tuberculosis Intercurrent Events Tuberculosis in People with HIV Infection Pulmonary Tuberculosis Primary Tuberculosis in Childhood Postprimary (Adult-Type) Pulmonary Tuberculosis Lower Lobe and Endobronchial Tuberculosis Progressive Lower Lobe Disease in Older Persons Endobronchial Tuberculosis Pulmonary Tuberculosis in AIDS Tuberculomas Symptoms Physical Examination Radiographic Findings Laboratory Findings Diagnosis Fiberoptic Bronchoscopy Tuberculosis Diagnosed at Autopsy Tuberculosis and Cancer Therapy Antituberculous Drugs Isoniazid Rifampin Rifapentine Pyrazinamide Ethambutol Streptomycin Fluoroquinolones Bedaquiline Second-Line Agents Third-Line Agents Agents under Development Selecting a Drug Regimen Standard Regimens Based on Isoniazid and Rifampin Directly Observed Treatment Regimens of Less Than 6 Months for Minimal Disease Fixed-Dose Combination Tablets Treatment of Multidrug-Resistant Tuberculosis Therapy for Extensively Drug-Resistant Tuberculosis Course of Therapy and Duration of Observation Treatment Algorithm Re-treatment Other Forms of Treatment Corticosteroids Treatment of Tuberculosis in HIV-Infected Patients Immune Reconstitution Inflammatory Syndrome Duration of Therapy Other Special Treatment Circumstances Childhood Pregnancy Uremia and End-Stage Renal Disease Liver Disease Patients Receiving Immunosuppressive Drugs Treatment of Latent Tuberculous Infection Drug Regimens Risk for Isoniazid Hepatotoxicity during Treatment of Latent Tuberculous Infection Treatment of Contacts of Active Cases Treatment of Quiescent, Previously Untreated Pulmonary Tuberculosis Treatment of Individuals with Recent Infection Treating Latent Tuberculous Infection in Persons with HIV Infection M. tuberculosis Infection in Persons with Additional Risk Factors Pregnant Women The Nursing Home Problem Vaccination Extrapulmonary Tuberculosis AIDS and Extrapulmonary Tuberculosis General Comments on Treatment of Extrapulmonary Tuberculosis Miliary Tuberculosis Usual (Acute) Miliary Tuberculosis Cryptic Miliary Tuberculosis and Late Generalized (Chronic Hematogenous) Tuberculosis Nonreactive Tuberculosis Miliary Tuberculosis and Hematologic Abnormalities Primary Hepatic Tuberculosis Miliary Tuberculosis in AIDS CNS Tuberculosis: Tuberculous Meningitis Pathologic Features Clinical Manifestations Therapy Tuberculomas Tuberculous Spinal Meningitis Tuberculous Pleurisy (Serofibrinous Pleurisy with Effusion) Types of Tuberculous Pleurisy Early Postprimary Pleurisy with Effusion Pleurisy with Effusion Complicating Chronic Pulmonary Tuberculosis Pleurisy with Effusion Complicating Miliary Tuberculosis Clinical Manifestations and Diagnosis Therapy Tuberculous Empyema and Bronchopleural Fistula Tuberculous Pericarditis Clinical Manifestations and Diagnosis Therapy Skeletal Tuberculosis: Pott’s Disease (Tuberculous Spondylitis) Clinical Manifestations Abscess and Sinus Formation Pott’s Paraplegia Therapy Peripheral Osteoarticular Tuberculosis Genitourinary Tuberculosis: Renal Tuberculosis Male Genital Tuberculosis Genitourinary Tuberculosis in AIDS Female Genital Tuberculosis Gastrointestinal Tuberculosis Gastrointestinal Tuberculosis in AIDS Tuberculous Peritonitis Tuberculous Lymphadenitis (Scrofula): Peripheral Nodes Mediastinal Tuberculous Lymphadenopathy Fibrosing Mediastinitis Mesenteric Tuberculous Lymphadenitis Cutaneous Tuberculosis Tuberculous Laryngitis Tuberculous Otitis Miscellaneous Conditions Key References References Chapter 252 252 Mycobacterium leprae (Leprosy) Keywords Short View Summary Epidemiology Global Epidemiology United States Microbiology and Genome Sequence Immunology Clinical Manifestations and Immunologic Spectrum of Leprosy Mechanisms of Immunity Pathogenesis of Nerve Damage Direct Nerve Damage by Mycobacterium leprae Immunologically Mediated Peripheral Nerve Damage in Leprosy Clinical Manifestations Differential Diagnosis Diagnosis Reactions Reversal Reactions (Lepra Type 1 Reactions) Erythema Nodosum Leprosum (Lepra Type 2 Reactions) Lucio’s Phenomenon Long-Term Complications Therapy Antimicrobial Therapy Background Agents to Treat Leprosy Regimens to Treat Leprosy World Health Organization Regimens U.S. Regimens Response to Therapy Role of Resistance Testing Relapses and Treatment of Relapses Therapy for Reactions Reversal Reactions Erythema Nodosum Leprosum Supportive Care and Rehabilitation Prevention of Leprosy Role of Bacillus Calmette-Guérin Vaccine in Leprosy Prevention Leprosy in Special Patient Populations Leprosy and Human Immunodeficiency Virus Infection Leprosy in Other Immunocompromised Hosts Key References References Chapter 253 253 Mycobacterium avium Complex Keywords Short View Summary Epidemiology Reservoir and Route of Acquisition Pulmonary Disease Disseminated Disease Lymphadenitis Pathogen Classification and Microbiology Organism Virulence Pathogenesis Pulmonary Disease Disseminated Disease Lymphadenitis Host Immunity Pulmonary Disease Disseminated Disease Lymphadenitis Clinical Manifestations Pulmonary Disease Disseminated Disease Lymphadenitis Other Sites Diagnosis Pulmonary Disease Mycobacterium avium Complex Hypersensitivity Pneumonitis Disseminated Disease Lymphadenitis Other Sites Treatment Principles of Treatment Tolerability Drug Interactions Drug Dosing in Patients with Impaired Renal Function Treatment of Macrolide-Resistant Mycobacterium avium Complex Disease Immunomodulatory Treatment of Mycobacterium avium Complex Disease Specific Treatment Plans Pulmonary Mycobacterium avium Complex Drug Treatment Surgery Hypersensitivity Pneumonitis Disseminated Disease Lymphadenitis Prophylaxis Key References References Chapter 254 254 Infections Caused by Nontuberculous Mycobacteria Other than Mycobacterium avium Complex Keywords Short View Summary Introduction Rapidly Growing Mycobacteria Slowly Growing Mycobacteria Intermediately Growing Mycobacteria Nontuberculous Mycobacteria and the Environment Nontuberculous Mycobacteria and Clinical Disease Pulmonary Disease Geography of Common Nontuberculous Mycobacteria Species Nontuberculous Mycobacteria Species Associated Infrequently with Pulmonary Disease Pulmonary Syndromes Associated with Nontuberculous Mycobacteria Other than Mycobacterium avium Complex Clinical Nontuberculous Mycobacteria Disease Treatment of Mycobacterium kansasii Lung Disease Treatment of Mycobacterium abscessus subsp. abscessus (M. abscessus) and Mycobacterium abscessus subsp. massiliense (M. massiliense) Lung Disease Treatment of Other Nontuberculous Mycobacteria Lymphadenitis Localized Cutaneous and Soft Tissue Infections Mycobacterium marinum Rapidly Growing Mycobacteria Health Care–Associated Infections Skin/Soft Tissue Diagnosis and Treatment Infection of Tendon Sheaths, Bones, Bursae, and Joints Disseminated Disease Human Immunodeficiency Virus Disease Non–Human Immunodeficiency Virus Disease Catheter-Related Infections Miscellaneous Infections Laboratory Aspects Stain and Culture Identification Susceptibility Testing: Rapidly Growing Mycobacteria Susceptibility Testing: Slowly Growing Nontuberculous Mycobacteria Strain Comparison Key References References Chapter 255 255 Nocardia Species Keywords Short View Summary Classification Ecology and Epidemiology Pathology and Pathogenesis Specific Virulence Determinants Clinical Epidemiology Clinical Manifestations Superficial Infection and Mycetoma Pulmonary Manifestations Disseminated Disease Keratitis Colonization Laboratory Diagnosis Molecular Identification of Nocardia Species Management Antimicrobial Selection Trimethoprim-Sulfamethoxazole Other Agents Empiric Therapy Keratitis Surgical Management Duration of Therapy and Prognosis Prophylaxis Clinical Outcomes Key References References Chapter 256 256 Agents of Actinomycosis Keywords Short View Summary Etiologic Agents Epidemiology Pathogenesis and Pathology Clinical Manifestations Oral-Cervicofacial Disease Thoracic Disease Endocarditis, Pericarditis, and Mediastinal Disease Abdominal Disease Pelvic Disease Central Nervous System Disease Musculoskeletal Disease Disseminated Disease Diagnosis Therapy Key References References Chapter 257 257 Introduction to Mycoses Keywords Changes in How Fungi are Identified Identification by DNA Sequence Cryptic Species A Conservative Approach to Name Changes Identification by MALDI-TOF Mass Spectrometry Common Features of Pathogenic Fungi Yeasts and Molds Dimorphic Fungi Diagnosis of Mycoses Microscopic Appearance of Fungi Tissue Stains Fresh Clinical Specimens Serologic Diagnosis Epidemiology References Chapter 258 258 Candida Species Keywords Short View Summary Pathogen Epidemiology and Ecology Pathogenesis and Immunology Clinical Manifestations Mucous Membrane Infections Thrush Candida Esophagitis Nonesophageal, Mucous Membrane, Gastrointestinal Candidiasis Candida Vaginitis Cutaneous Candidiasis Syndromes Generalized Cutaneous Candidiasis Erosio Interdigitalis Blastomycetica Candida Folliculitis Candida Balanitis Cutaneous Lesions of Disseminated Candidiasis Intertrigo Paronychia and Onychomycosis Diaper Rash Perianal Candidiasis Chronic Mucocutaneous Candidiasis Deep Organ Involvement Central Nervous System Candidiasis Respiratory Tract Candidiasis Cardiac Candidiasis Candida Endocarditis Urinary Tract Candidiasis Candida Arthritis, Osteomyelitis, Costochondritis, and Myositis Candida Infection of Peritoneum, Liver, Spleen, and Gallbladder Candida Infection of Vasculature Ocular Candidiasis Endogenous Ocular Candidiasis Exogenous Ocular Candidiasis Syndrome of Candidemia and Disseminated Candidiasis Miscellaneous Candida Infections “Chronic Candidiasis Syndrome” or “The Yeast Connection” Treatment and Prophylaxis General Comments Systemic Drugs for Candidiasis Polyenes Triazoles Echinocandins Flucytosine Candidemia in Non-neutropenic Patients Candidemia in Neutropenic Patients Candida Infections of the Cardiovascular System Central Nervous System Candida Infection Candida Peritonitis, Gallbladder Infection, and Intra-abdominal Abscesses Urinary Candidiasis Mucocutaneous Candidiasis Chronic Mucocutaneous Candidiasis Ocular Candidiasis Key References References Chapter 259 259 Aspergillus Species Keywords Short View Summary Mycology Epidemiology Pathogenicity and Host Defenses Clinical Manifestations Allergic Manifestations of Disease Allergic Bronchopulmonary Aspergillosis Other Allergic Manifestations Saprophytic Colonization and Superficial Aspergillosis Fungus Balls due to Aspergillus Other Superficial or Colonizing Syndromes of Aspergillosis Invasive Syndromes Caused by Aspergillus Invasive Pulmonary Aspergillosis Tracheobronchitis Sinusitis Disseminated Infection Other Invasive Syndromes Cerebral Aspergillosis Bone Aspergillosis Cutaneous Infection Other Sites Diagnosis and Antifungal Resistance Therapy Primary Antifungal Therapy Voriconazole Alternative Primary Therapy Lipid Amphotericin Formulations Other Antifungal Agents Amphotericin B Deoxycholate Other Polyenes Other Triazoles Echinocandins Combination Antifungal Therapy Adjuvant Therapy Approach to Therapy Prevention and Prophylaxis Key References References Chapter 260 260 Agents of Mucormycosis and Entomophthoramycosis Keywords Short View Summary Etiology Insights from Genomic Sequencing Epidemiology Acquisition of Infection Patient Populations at Risk Incidence of Mucormycosis Pathogenesis and Immunology Host Immune Response against Mucormycosis Role of Iron Uptake in Mucormycosis Pathogenesis Histopathology Clinical Manifestations of Mucormycosis Rhinocerebral Infections Clinical Presentation Radiology Pulmonary Infections Clinical Presentation Radiology Pulmonary Mucormycosis in Less Severely Immunocompromised Patients Skin and Soft Tissue Infections Gastrointestinal Mucormycosis Disseminated Mucormycosis Less Common Presentations of Mucormycosis Diagnosis Culture Diagnosis Histopathologic Diagnosis Species Identification Differentiating Mucormycosis from Other Molds Antifungal Susceptibility Combination Therapy Treatment Antifungal Therapy Lipid Amphotericin B Formulations Triazoles Combination Therapy Treatment Duration Prophylaxis Surgical Management Adjunctive Therapies Prognosis Entomophthoramycosis Conidiobolomycosis Basidiobolomycosis Diagnosis Differential Diagnosis Therapy and Prevention Key References References Chapter 261 261 Sporothrix schenckii Keywords Short View Summary Mycology Epidemiology Clinical Syndromes Lymphocutaneous Sporotrichosis Extracutaneous Sporotrichosis Multifocal Extracutaneous Sporotrichosis Clinical Manifestations of Sporotrichosis in the HIV-Infected Patient Diagnosis Therapy Therapy of Patients with Acquired Immunodeficiency Syndrome Itraconazole Blood Level Monitoring Prognosis Key References References Chapter 262 262 Agents of Chromoblastomycosis Keywords Short View Summary Etiologic Agents Epidemiology Pathology and Pathogenesis Clinical Manifestations Diagnosis Therapy Key References References Chapter 263 263 Agents of Mycetoma Keywords Short View Summary Etiologic Agents Epidemiology Pathology and Pathogenesis Clinical Manifestations Diagnosis Therapy Prevention Key References References Chapter 264 264 Cryptococcosis (Cryptococcus neoformans and Cryptococcus gattii) Keywords Short View Summary History Mycology Life Cycle and Genetics Taxonomy Identification Ecology Cryptococcus neoformans Serotypes A, D, and AD (var. neoformans and var. grubii) Cryptococcus gattii Serotypes B and C Epidemiology Pathogenicity Capsule Melanin High-Temperature Growth Other Pathogenicity Factors Host Responses Pathogenesis Clinical Manifestations Lung Central Nervous System Skin Prostate Eye Other Body Sites Immune Reconstitution Inflammatory Syndrome Laboratory Diagnosis Microscopic Examination Cultures Antigen Detection Radiology Management In Vitro Drug Analysis Treatment Strategies Cryptococcal Meningitis Prognosis Prevention Key References References Chapter 265 265 Histoplasma capsulatum (Histoplasmosis) Keywords Short View Summary History Ecology and Epidemiology Mycology Pathogenesis Innate Immunity Adaptive Immunity Granulomas Delayed-type Hypersensitivity Pulmonary Histoplasmosis Acute Infections Acute Primary Infection Symptoms Clinical Findings Pericarditis Differential Diagnosis Acute Reinfection Complications of Primary Histoplasmosis Histoplasmoma Mediastinal Granuloma and Fibrosis Chronic Pulmonary Histoplasmosis Symptoms Laboratory Findings Pathology Noncavitary Chronic Pulmonary Disease Progressive Disseminated Histoplasmosis Incidence Reactivation versus New Exposure Pathology Acute Progressive Disseminated Histoplasmosis Laboratory Abnormalities Progressive Disseminated Histoplasmosis and Human Immunodeficiency Virus Laboratory Abnormalities in Coinfection Subacute Progressive Disseminated Histoplasmosis Clinical Features Endovascular Infection Central Nervous System Involvement Chronic Progressive Disseminated Histoplasmosis Clinical Findings Ocular Histoplasmosis African Histoplasmosis Diagnosis Fungal Culture Antigen Detection Serology Histochemical Identification Miscellaneous Laboratory Tests Therapy Acute Pulmonary Histoplasmosis Mediastinal Granuloma, Mediastinal Fibrosis, and Histoplasmoma Cavitary Pulmonary Histoplasmosis Acute Progressive Disseminated Histoplasmosis Subacute and Chronic Progressive Disseminated Histoplasmosis Meningitis Endocarditis Pericarditis Arthropathies Presumed Ocular Histoplasmosis Other Considerations Immune Reconstitution Syndrome and Histoplasma Prevention Prophylaxis of Immunocompromised Persons Other Considerations Key References References Chapter 266 266 Blastomycosis Keywords Short View Summary History Organism Epidemiology Pathogenesis and Virulence Clinical Manifestations Diagnosis Treatment Key References References Chapter 267 267 Coccidioidomycosis (Coccidioides Species) Keywords Short View Summary Mycology Mycelial (Saprobic) Growth Spherule (Parasitic) Growth Epidemiology Geographic Range Rates of Coccidioidal Infection Pathogenesis and Control Histopathology Host Defenses Clinical Manifestations Early Respiratory Infection Pulmonary Nodules and Cavities Chronic Fibrocavitary Pneumonia Extrapulmonary Dissemination Diagnosis Direct Examination and Culture Serologic Testing Tube Precipitin Antibodies Complement-Fixing Antibodies Immunodiffusion Tests Enzyme-Linked Immunoassays Latex Tests Skin Testing Other Approaches to Diagnosis Management General Approaches Therapy Early Uncomplicated Infections Diffuse Pneumonia Pulmonary Cavity Chronic Fibrocavitary Pneumonia Extrapulmonary Dissemination New Therapies Prevention Key References References Chapter 268 268 Dermatophytosis (Ringworm) and Other Superficial Mycoses Keywords Short View Summary Dermatophytosis Dermatophytes Epidemiology Zoophilic Dermatophyte Infections Geophilic Dermatophyte Infections Anthropophilic Dermatophyte Infections Age Incidence Pathogenesis Clinical Manifestations Tinea Pedis Tinea Cruris Tinea Corporis Tinea Imbricata Tinea Manuum Tinea Faciei Tinea Capitis Onychomycosis Caused by Dermatophytes Deep Dermatophyte Infections Dermatophyte “Id” Reactions Laboratory Diagnosis Therapy Neoscytalidium Infections Clinical Manifestations Diagnosis Therapy Other Forms of Onychomycosis Pityriasis Versicolor Organisms Pathogenesis Clinical Manifestations Therapy Other Malassezia Infections Malassezia Folliculitis Seborrheic Dermatitis Clinical Manifestations Therapy Tinea Nigra White Piedra Black Piedra Key References References Chapter 269 269 Paracoccidioidomycosis Keywords Short View Summary Description of the Pathogen Ecology and Epidemiology Pathogenesis Pathogenesis and the Immune Response Innate Immune Response Acquired Immune Response Humoral Immune Responses Immunoregulation, Immunomodulation, and Vaccines Clinical Manifestations Characteristics of the Lesions Lungs Mucosa Skin Lymph Nodes Adrenals Other Lesions Paracoccidioidomycosis in HIV-Infected Patients Paracoccidioidomycosis and Cancer Differential Diagnosis Treatment Sulfonamides Amphotericin B Azole Derivatives Laboratory Diagnosis Direct Examination Histopathologic Studies Cultures Immune-Based Diagnostic Tests Molecular Testing Skin Tests Key References References Chapter 270 270 Uncommon Fungi and Related Species Keywords Short View Summary Pseudallescheria Boydii Scedosporium Prolificans Dark-Walled Fungi and Agents of Phaeohyphomycosis Fusarium Spp. Other Opportunistic Molds Trichosporon Spp. Malassezia Furfur Other Uncommon Yeasts Penicillium Marneffei Lacazia Loboi Agents of Adiaspiromycosis (Emmonsia Spp.) Emmonsia Pasteuriana Prototheca Spp. Pythium Spp. Rhinosporidium Seeberi Summary Key References References Chapter 271 271 Pneumocystis Species Keywords Short View Summary Pathogen Epidemiology Pathology and Pathogenesis Clinical Manifestations Other Clinical Manifestations Diagnosis Course and Prognosis Treatment Prevention Chemoprophylaxis Stopping Prophylaxis Boosting Host Immune Response Preventing Exposure Key References References Chapter 272 272 Microsporidiosis Keywords Short View Summary General Characteristics Phylogeny of the Microsporidia Epidemiology Immunology Pathology and Pathogenesis Gastrointestinal Tract Infections Genitourinary Tract Infection Central Nervous System Infection Ocular Infection Musculoskeletal Infection Sinus and Respiratory Infection Skin Clinical Manifestations Microsporidian Infection in Non-AIDS Patients Microsporidian Infection in AIDS Patients Enterocytozoonidae Encephalitozoonidae Other Microsporidia Diagnosis Therapy Gastrointestinal and Systemic Disease Ocular Disease Prevention Key References References Chapter 273 273 Introduction to Protozoal Diseases Keywords Key References References Chapter 274 274 Entamoeba Species, Including Amebic Colitis and Liver Abscess Keywords Short View Summary Organism Species of Entamoeba Genotypes of Entamoeba histolytica Life Cycle Metabolism Cell Biology Genome Structure Pathogenesis Adherence Cytolysis Phagocytosis Role of Bacteria Cysteine Proteinases Role of Leptin in Host Resistance Immune Response and Immunity Innate Immunity Neutrophils Macrophages Natural Killer Cells and Natural Killer T Cells Activated Mast Cells Complement-Mediated Lysis of Entamoeba histolytica Intestinal Epithelial Cells Acquired Immunity Mucosal Immunoglobulin A Response Cell-Mediated Response Epidemiology Clinical Manifestations Asymptomatic Intraluminal Amebiasis Amebic Diarrhea Amebic Dysentery or Colitis Amebic Liver Abscess Metastatic Amebiasis Diagnosis Stool Ova and Parasite Examination Culture Colonoscopy and Biopsy Polymerase Chain Reaction Testing for Amebiasis Antigen Testing for Amebiasis Serologic Tests for Amebiasis Therapy Prevention Key References References Chapter 275 275 Free-Living Amebae Keywords Short View Summary Overview Organisms Naegleria Acanthamoeba Balamuthia Other Free-Living Amebae Reported in Human Disease Epidemiology Naegleria Acanthamoeba Balamuthia Pathogenesis and Pathologic Findings Naegleria Acanthamoeba Balamuthia Clinical Manifestations Naegleria Acanthamoeba Balamuthia Laboratory Diagnosis Naegleria Acanthamoeba Balamuthia Therapy Naegleria Clinical Evidence Animal Models and in Vitro Assays Recommendations Acanthamoeba Granulomatous Amebic Encephalitis and Disseminated Disease Clinical Evidence Animal Models and in Vitro Assays Recommendations Acanthamoeba Keratitis Recommendations Balamuthia Clinical Evidence In Vitro Assays Recommendations Prevention Resources Key References References Chapter 276 276 Malaria (Plasmodium Species) Keywords Short View Summary The Malaria Problem Plasmodium and Its Life Cycle Pathophysiology The Malaria Paroxysm and General Considerations Plasmodium falciparum Cerebral Malaria Hypoglycemia Anemia Pulmonary Edema and Respiratory Distress Metabolic (Lactic) Acidosis Malaria of Pregnancy Plasmodium vivax and Plasmodium ovale Plasmodium malariae Plasmodium knowlesi Genetic Resistance Hemoglobins S, C, and E Thalassemias Hemoglobin F Glucose-6-Phosphate Dehydrogenase Deficiency Southeast Asian Ovalocytosis ABO Blood Groups Duffy Antigen Receptor for Chemokines Negativity Acquired Immunity and Antigenic Variation Epidemiology of Malaria Distribution of Drug Resistance Antimalarial Drugs: Mechanisms of Action and Resistance Chloroquine Amodiaquine Sulfadoxine-Pyrimethamine Atovaquone-Proguanil (Malarone) Doxycycline Mefloquine, Quinidine, and Quinine Artemisinin Derivatives Clinical Presentation and Diagnosis of Malaria History and Physical Examination Thick and Thin Blood Smears Rapid Diagnostic Tests Other Laboratory Tests Severe P. falciparum Malaria Distinguishing Malaria From Other Illnesses with Similar Clinical Presentations Influenza Enteric Fever Bacteremia/Sepsis Dengue Fever Acute Schistosomiasis (Katayama Fever) Leptospirosis African Tick Fever East African Trypanosomiasis (Sleeping Sickness) Yellow Fever Therapy General Principles Uncomplicated Malaria Chloroquine Phosphate Atovaquone-Proguanil (Malarone) Artemisinin-Based Combination Therapies Quinine plus Doxycycline Mefloquine Standby Emergency Treatment of Uncomplicated Malaria in Travelers Intermittent Presumptive Treatment in Infants, Children, and Pregnant Women Severe Malaria Quinidine Gluconate Artemisinins Quinine Dihydrochloride Bacteremia and Sepsis in Severe Malaria Exchange Transfusion in Severe Malaria Nonfalciparum Malaria Prevention Risk Assessment Chemoprophylaxis Areas with Chloroquine-Sensitive Malaria Areas with Mefloquine-Sensitive Malaria All Areas Mosquito Repellent and Avoidance Measures Vaccination Key References References Chapter 277 277 Leishmania Species: Keywords Short View Summary Overview and General Principles Life Cycle Taxonomy and Classification Epidemiology Pathogenesis Diagnosis Visceral Leishmaniasis Epidemiology Pathogenesis and Natural History of Visceral Leishmaniasis Clinical Manifestations of Kala-Azar Visceral Leishmaniasis in Patients with AIDS Viscerotropic Leishmaniasis Post–Kala-Azar Dermal Leishmaniasis Diagnosis Differential Diagnosis Cutaneous Leishmaniasis Epidemiology Pathogenesis and Immunology Clinical Manifestations of New World and Old World Cutaneous Leishmaniasis Diffuse Cutaneous Leishmaniasis Leishmaniasis Recidivans Disseminated Leishmaniasis Diagnosis of Cutaneous Leishmaniasis New World Mucosal Leishmaniasis Diagnosis Treatment of Leishmaniasis General Principles Visceral Leishmaniasis Liposomal Amphotericin B Pentavalent Antimony Miltefosine Pentamidine and Amphotericin B Deoxycholate Paromomycin Response to Treatment Combination Therapy for Visceral Leishmaniasis Treatment of Post–Kala-Azar Dermal Leishmaniasis Treatment of Cutaneous Leishmaniasis Old World Cutaneous Leishmaniasis New World Cutaneous Leishmaniasis Antimony Liposomal Amphotericin B Pentamidine Ketoconazole Miltefosine Diffuse Cutaneous Leishmaniasis New World Mucosal Leishmaniasis Prevention Key References References Chapter 278 278 Trypanosoma Species (American Trypanosomiasis, Chagas’ Disease): Keywords Short View Summary Chagas’ Disease Life Cycle and Transmission Pathology Epidemiology Clinical Manifestattions Immunosuppression and Transplantation in T. cruzi–Infected Patients Diagnosis Therapy Prevention Key References References Chapter 279 279 Agents of African Trypanosomiasis (Sleeping Sickness) Keywords Short View Summary Parasites and Their Transmission Pathogenesis and Pathology Epidemiology West African Trypanosomiasis East African Trypanosomiasis Clinical Course West African Trypanosomiasis East African Trypanosomiasis Diagnosis Therapy Prevention Key References References Chapter 280 280 Toxoplasma gondii Keywords Short View Summary Etiology Organism Stages Oocyst Tachyzoite Tissue Cyst Transmission and Epidemiology Pathogenesis and Immunity Genetic Susceptibility Pathology Lymph Node Central Nervous System Lung Eye Skeletal and Heart Muscle Other Organ Systems Clinical Manifestations Toxoplasmosis in the Immunocompetent Patient Toxoplasmosis in the Immunodeficient Patient Toxoplasmosis in the Solid-Organ Transplant Patient Heart Transplantation Kidney Transplantation Liver Transplantation Toxoplasmosis in the Bone Marrow Transplant and Hematopoietic Stem Cell Transplant Recipient Toxoplasmosis in the AIDS Patient Ocular Toxoplasmosis in Immunocompetent Patients Toxoplasmosis during Pregnancy Congenital Toxoplasmosis Diagnosis Serologic Tests for Demonstration of Antibody Immunoglobulin G Antibodies Sabin-Feldman Dye Test Indirect Fluorescent Antibody Test Agglutination and AC/HS Tests Immunoglobulin G Enzyme-Linked Immunosorbent Assay Immunoglobulin G Avidity Test Immunoglobulin M Antibodies Immunoglobulin M Indirect Fluorescent Antibody Test Immunoglobulin M Enzyme-Linked Immunosorbent Assay Immunoglobulin M Immunosorbent Agglutination Assay Immunoglobulin A Antibodies Immunoglobulin E Antibodies Polymerase Chain Reaction Histologic Diagnosis Isolation of Toxoplasma gondii Radiologic Methods Cerebrospinal Fluid Abnormalities Diagnosis of Specific Clinical Entities Toxoplasmosis in the Immunocompetent Patient Toxoplasmosis in the Immunodeficient Patient Ocular Toxoplasmosis Toxoplasma gondii Infection in Pregnancy Congenital Infection in the Fetus and Newborn Therapy Therapy Regimens in Specific Clinical Entities Toxoplasmosis in the Immunocompetent Patient Toxoplasmosis in the Immunodeficient Patient Ocular Toxoplasmosis Acute Acquired Toxoplasma Infection in Pregnant Women Congenital Infection Prevention General Methods Serologic Screening and Prophylaxis Acute Toxoplasma gondii Infection and Toxoplasmosis in the Immunodeficient Patient Congenital Toxoplasma gondii Infection and Toxoplasmosis Acknowledgments Key References References Chapter 281 281 Giardia lamblia Keywords Short View Summary Description of the Pathogen Epidemiology Pathogenesis and Immune Response Clinical Manifestations Diagnosis Therapy Prevention Key References References Chapter 282 282 Trichomonas vaginalis Keywords Short View Summary Taxonomy Epidemiology Clinical Manifestations Diagnosis Therapy Complications Key References References Chapter 283 283 Babesia Species Keywords Short View Summary Epidemiology United States: Babesia microti Geographic Distribution Incidence and Prevalence Modes of Transmission Tick Bite Transfusion Transplacental/Perinatal Transmission Risk Factors United States: Other Babesia Species Europe: Babesia divergens Europe: Other Babesia Species Other Regions Microbiology Life Cycle of Babesia microti Acquisition by the Tick Transmission to Vertebrate Hosts Classification of Babesia Species Morphology and Life Cycle Phylogeny Whole Genome Clinical Manifestations Babesia microti Infection Infection with Other Babesia Species Pathogenesis Erythrocyte Modification and Rupture Inflammatory and Immune Response Diagnosis Microscopy Parasite Nucleic Acid Amplification Serology Therapy Babesia microti Infection Severe Babesia microti Infection First-Line Therapy Alternative Regimens Persistent Relapsing Infection Exchange Transfusion Mild Babesia microti Infection Infection with Other Babesia Species Prevention Acknowledgments Key References References Chapter 284 284 Cryptosporidiosis (Cryptosporidium Species) Keywords Short View Summary The Parasites Epidemiology Pathology and Pathogenesis Host Response and Immunity Clinical Manifestations Immunocompetent Individuals in Developed Countries Childhood Diarrhea in Developing Countries Cryptosporidium and Malnutrition Cryptosporidiosis in HIV Infection Diagnosis Management Prevention Key References References Chapter 285 285 Cyclospora cayetanensis, Cystoisospora (Isospora) belli, Sarcocystis Species, Balantidium coli, and Blastocystis Species Keywords Short View Summary Coccidia Other Than Cryptosporidia Cyclospora Life Cycle Epidemiology Clinical Manifestations Diagnosis Therapy Cystoisospora (Isospora) belli Life Cycle Epidemiology Clinical Manifestations Diagnosis Therapy Sarcocystis Species Life Cycle Epidemiology Clinical Manifestations Diagnosis Therapy Balantidium coli Life Cycle Epidemiology Clinical Manifestations Diagnosis and Therapy Blastocystis Species Life Cycle Epidemiology Clinical Manifestations Diagnosis Therapy Acknowledgment Key References References Chapter 286 286 Human Illness Associated with Harmful Algal Blooms Keywords Short View Summary Ciguatera Fish Poisoning Paralytic Shellfish Poisoning Neurotoxic Shellfish Poisoning Diarrhetic Shellfish Poisoning Amnesic Shellfish Poisoning Azaspiracid Shellfish Poisoning Lyngbya/Cyanobacteria Exposure Syndromes Pfiesteria-Associated Syndrome References Chapter 287 287 Introduction to Helminth Infections Keywords Biology of Helminths Epidemiology Pathogenesis and Host-Parasite Relationship Diagnosis and Treatment of Helminth Infections Prevention and Control Key References References Chapter 288 288 Intestinal Nematodes (Roundworms) Keywords Short View Summary Ascariasis Life Cycle Epidemiology Clinical Syndromes Diagnosis Management Trichuriasis Life Cycle Epidemiology Clinical Syndromes Diagnosis Management Hookworm Life Cycle Epidemiology Clinical Syndromes Diagnosis Management Prevention and Control of Ascariasis, Trichuriasis, and Hookworm Infection Strongyloidiasis Life Cycle Epidemiology Clinical Syndromes Diagnosis Management Prevention of Hyperinfection and Disseminated Strongyloidiasis Enterobiasis Life Cycle Epidemiology Clinical Syndromes Diagnosis Management Key References References Chapter 289 289 Tissue Nematodes (Trichinellosis, Dracunculiasis, Filariasis, Loiasis, and Onchocerciasis) Keywords Short View Summary Trichinellosis Life Cycle of Trichinella Epidemiology Pathogenesis and Pathology Clinical Manifestations Diagnosis Therapy Prevention Haycocknema Perplexum Infection Dracunculiasis Life Cycle of the Parasite Epidemiology Clinical Manifestations Diagnosis and Therapy Control and Eradication Filariases Lymphatic Filariasis Life Cycle of the Parasite Epidemiology Clinical Manifestations Pathogenesis and Pathology Diagnosis Therapy Prevention, Control, and Eradication Tropical Pulmonary Eosinophilia Loiasis Life Cycle of the Parasite Epidemiology Clinical Manifestations Diagnosis Therapy Prevention and Control Onchocerciasis Life Cycle of the Parasite Epidemiology Pathology and Clinical Manifestations Diagnosis Therapy Prevention and Control Mansonellosis Zoonotic Filariae Reported to Cause Human Disease References Chapter 290 290 Trematodes (Schistosomes and Liver, Intestinal, and Lung Flukes) Keywords Short View Summary Schistosomes Life Cycle Epidemiology Pathogenesis Clinical Syndromes Schistosome Dermatitis (“Swimmer’s Itch”) Acute Schistosomiasis (Katayama Fever) Chronic Schistosomiasis Diagnosis Therapy Prevention and Control of Schistosomiasis Liver Flukes Clonorchiasis and Opisthorchiasis Clinical Manifestations Diagnosis and Therapy Fascioliasis Clinical Manifestations Diagnosis Therapy Intestinal Flukes Fasciolopsiasis Heterophyiasis, Metagonimiasis, and Haplorchiasis Echinostomiasis Diagnosis and Therapy Lung Flukes Paragonimiasis Clinical Manifestations Diagnosis and Therapy Prevention of Foodborne Fluke Infections Key References References Chapter 291 291 Tapeworms (Cestodes) Keywords Short View Summary Cestode Biology Parasite Life Cycle Disease Pathogenesis and Immunology Intestinal Tapeworms Diphyllobothrium latum Hymenolepis nana Taenia saginata Taenia solium Other Species Causing Tapeworm Infection in Humans Diagnosis Therapy Niclosamide Praziquantel Invasive Cestode Infections Cysticercosis Echinococcosis (Hydatid and Alveolar Cyst Disease) Other Invasive Cestodes Prevention Key References References Chapter 292 292 Visceral Larva Migrans and Other Uncommon Helminth Infections Keywords Short View Summary Visceral Larva Migrans (Toxocariasis) Life Cycle in the Dog Infection in Humans Prevalence Clinical Manifestations Diagnosis Differential Diagnosis Treatment and Management Prevention Ocular Larva Migrans Baylisascariasis Anisakiasis Life Cycle in Marine Mammals Clinical Syndrome Laboratory Findings Diagnosis Treatment Prevention Cutaneous Larva Migrans (Creeping Eruption) Eosinophilic Meningitis Gnathostomiasis Life Cycle Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Abdominal Angiostrongyliasis Eosinophilic Gastroenteritis Dirofilariasis Capillariasis Nanophyetiasis Swimmer’s Itch Key References References Chapter 293 293 Introduction to Ectoparasitic Diseases Keywords Taxonomy of Ectoparasites Epidemiology of Ectoparasitic Diseases Mechanisms of Ectoparasite-Borne Diseases and Injuries Conclusions Key References References Chapter 294 294 Lice (Pediculosis) Keywords Short View Summary Epidemiology Diagnosis Clinical Manifestations and Differential Diagnosis Head Lice Body Lice Crab Lice (Pediculosis Pubis) Therapy Therapy for Pediculosis Capitis Therapy for Body Lice Prevention Key References References Chapter 295 295 Scabies Keywords Short View Summary Epidemiology Transmission Clinical Manifestations Diagnosis Therapy Prevention Conclusion Key References References Chapter 296 296 Myiasis and Tungiasis Keywords Short View Summary Myiasis Epidemiology Clinical Manifestations Therapy Prevention and Control Flea Infestations Tungiasis Epidemiology Clinical Manifestations Therapy Prevention and Control Key References References Chapter 297 297 Mites, Including Chiggers Keywords Short View Summary Mite Taxonomy and Ecology Epidemiology and Outcomes of Mite Infestations Diagnosis and Management of Mite Infections Prevention of Mite Infections and Mite-Transmitted Infectious Diseases Conclusion Key References References Chapter 298 298 Ticks, Including Tick Paralysis Keywords Short View Summary Tick Biology, Behavior, and Taxonomy Epidemiology of Tick-Borne Infectious Diseases Tick-Borne Bacterial Infections Spirochetal Infections (Borrelioses) Spotted Fever Group Rickettsial Infections Q Fever Tularemia Tick-borne Ehrlichioses and Anaplasmosis Tick-Borne Protozoal Infections Babesial Infections Tick-Borne Viral Infections Tick-borne Viral Encephalitides Tick-borne Viral Hemorrhagic Fevers Tick-borne Coltiviruses Tick Paralysis Prevention and Control of Tick-Borne Infectious Diseases and Paralytic Poisonings Conclusion Key References References Chapter 299 299 Kawasaki Disease Keywords Short View Summary Epidemiology Etiology Clinical Manifestations Exanthem Conjunctival Injection Oropharyngeal Changes Peripheral Extremity Changes Cervical Lymphadenopathy Associated Clinical Features Arthritis Gastrointestinal Features Diagnosis Differential Diagnosis Pathology Genetics Therapy Cardiovascular Involvement Long-Term Outcome Key References References Chapter 300 300 Infection Prevention in the Health Care Setting Keywords Historical Background Role of Infection Control Surveillance Reporting Isolation Standard Precautions Hand Hygiene Gloves Personal Protective Equipment Injection Safety Bare Below the Elbows Transmission-Based Precautions Airborne Precautions Droplet Precautions Contact Precautions Outbreak Investigation and Management Education Employee Health Antimicrobial Stewardship Policy and Interventions Environmental Hygiene New Product Evaluation Regulatory Compliance Organization of the Infection Prevention Program Hospital Epidemiologist Infection Preventionists Infection Control Committee Future Challenges Key References References Chapter 301 301 Disinfection, Sterilization, and Control of Hospital Waste Keywords Definition of Terms Rational Approach to Disinfection and Sterilization Critical Items Semicritical Items Noncritical Items Disinfection of Health Care Equipment and Surfaces Chemical Disinfectants Alcohol Chlorine and Chlorine Compounds Glutaraldehyde Hydrogen Peroxide Improved Hydrogen Peroxide Iodophors Ortho-phthalaldehyde Peracetic Acid Peracetic Acid with Hydrogen Peroxide Phenolics Quaternary Ammonium Compounds Pasteurization Ultraviolet Light Sterilization Steam Sterilization Immediate-Use Steam Sterilization Ethylene Oxide “Gas” Sterilization Hydrogen Peroxide Gas Plasma Vaporized Hydrogen Peroxide Disinfection Reprocessing of Endoscopes OSHA Bloodborne Pathogen Standard Emerging Pathogens, Antibiotic-Resistant Bacteria, and Bioterrorism Agents Current Issues in Disinfection and Sterilization Inactivation of Creutzfeldt-Jakob Disease Agent Role of Surfaces in Disease Transmission Adequacy of Room Cleaning and Disinfection Using Chemical Germicides Improving Room Cleaning and Disinfection and Demonstrating the Effectiveness of Surface Decontamination in Reducing Health Care–Associated Infections “No Touch” Methods for Room Decontamination Ultraviolet Light for Room Decontamination Hydrogen Peroxide Systems for Room Decontamination Comparison of Ultraviolet Irradiation versus Hydrogen Peroxide for Room Decontamination Control of Hospital Waste Conclusion Key References References Chapter 302 302 Infections Caused by Percutaneous Intravascular Devices Keywords Short View Summary Pathogenesis Contamination of the Infusate Contamination of the Catheter Hub and Lumen (Intraluminal Source) Contamination of Skin at the Device Insertion Site (Extraluminal Source) Epidemiology Microbiology Diagnosis Device-Specific Issues Peripheral Intravenous Cannulization Central Venous Catheters: Short-term Issues Central Venous Catheters: Parenteral Nutrition Issues Central Venous Catheters: Long-term Issues Peripherally Inserted Central Venous Catheters Care and Maintenance of Implanted Central Venous Catheters Antimicrobial Lock Therapy Pulmonary Artery Catheters Arterial Lines, Transducers, and Transducer Domes Prevention of Device-Associated Bacteremia Before Insertion of Vascular Catheters At Insertion After Insertion Special Approaches for the Prevention of CLABSIs Antimicrobial Prophylaxis Antimicrobial Lock Prophylaxis Antimicrobial Catheters Other Prevention Issues Key References References Chapter 303 303 Nosocomial Pneumonia Keywords Short View Summary Health Care–Associated Pneumonia Epidemiology Morbidity and Mortality Pathophysiology Risk Factors Diagnosis Clinical Pulmonary Infection Score Summary and Recommendations for Clinical Diagnosis Microbiologic Evaluation Invasive versus Noninvasive Respiratory Tract Sampling Microbiology Treatment Empiric Therapy Vancomycin versus Linezolid for MRSA Coverage Combination versus Monotherapy for Gram-Negative Pathogens Aerosolized versus Intravenous Drug Delivery Tailoring and Deescalating Therapy Duration of Therapy Prevention Ventilator-assisted Pneumonia Prevention Bundles Ventilator-Assisted Pneumonia as a Quality Metric Key References References Chapter 304 304 Nosocomial Urinary Tract Infections Keywords Short View Summary Epidemiology Incidence and Prevalence Risk Factors Complications Microbiology Pathogenesis Diagnosis Significant Bacteriuria Symptoms and Signs Pyuria Prevention Prevention Strategies That Should Be Routine Prevention Components of Infection Control Programs Reduction of Unnecessary Catheterization Alternatives to Indwelling Urethral Catheterization Condom Catheterization Intermittent Catheterization Suprapubic Catheterization Techniques for Catheter Insertion and Maintenance Prevention Strategies with Possible Benefit Antimicrobial-Coated Catheters Prophylaxis with Antimicrobial Agents Systemic Antibiotics Methenamine Salts Other Measures Prevention Strategies with Little Benefit Enhanced Meatal Care Cranberry Products Bladder Irrigation with Antimicrobial Therapy or Saline Antimicrobial Drugs in the Drainage Bag Routine Catheter Change Prophylactic Antimicrobial Therapy at Catheter Removal or Replacement Strategies for Further Investigation Nosocomial Asymptomatic Bacteriuria Routine Screening and Treatment Management of Nosocomial Urinary Tract Infection Urine Culture and Catheter Replacement before Treatment Choice of Antibiotic Duration Fungal Urinary Tract Infection Summary Key References References Chapter 305 305 Health Care–Acquired Hepatitis Keywords Short View Summary Historical Background Current Status Fecal-Oral Transmission Hepatitis A Hepatitis E Bloodborne Transmission Hepatitis B Epidemiology Incidence after Exposure Reported Transmissions Worker-to-Patient Transmission. Patient-to-Worker Transmission. Dialysis Setting. Other Nosocomial Transmissions. Interventions and Management Vaccine Acceptance Rates Hepatitis C Seroprevalence Incidence after Exposure Reported Transmissions Worker-to-Patient Transmission. Dialysis Setting. Solid Tumor Transplantation. Other Nosocomial Transmissions. Management Hepatitis D Key References References Chapter 306 306 Transfusion- and Transplantation-Transmitted Infections Keywords Short View Summary Transfusion-Associated Infections Scope of Blood Transfusion Bloodborne Pathogens Human Immunodeficiency Virus Type 1 Human Immunodeficiency Virus Type 2 Human T-Cell Lymphotropic Virus Types 1 and 2 Other Retroviruses Hepatitis B and D Viruses Hepatitis C Virus West Nile Virus Herpesviruses Parvovirus B19 Hepatitis A and E Viruses Non–A-E Hepatitis Bacterial Pathogens Red Blood Cells Platelets Other Agents Transmitted Through Blood Components Tick-borne Bacteria Parasites Prions Infectious Diseases Transmitted Through Transplantation of Solid Organs and Other Tissues Transplant-Transmitted Bloodborne Pathogens Pathogens Causing Encephalitis Key References References Chapter 307 307 Human Immunodeficiency Virus in Health Care Settings Keywords Occupational HIV Transmission From Infected Patients to Health Care Personnel Reported Cases of Occupational HIV Infection Mechanisms of Occupational HIV Infection Definition of Occupational HIV Exposure Occupational HIV Exposure Transmission Risk Assessing Infection Risk in Populations of Exposed Health Care Personnel Factors Associated with HIV Infection Risk Characteristics Associated with Exposures Resulting in HIV Seroconversion in Health Care Workers Iatrogenic HIV Transmission from Infected Health Care Personnel to Patients Case Reports of HIV Transmission from Infected Providers to Patients Investigations of Patients Treated by HIV-Infected Health Care Personnel Iatrogenic Transmission Detected in the CDC’s HIV/AIDS Surveillance Database Provider-to-Patient Transmission Risk Assessment Nosocomial HIV Transmission from Infected Patients to Other Patients Primary Prevention Standard (Universal) Precautions Injury Prevention during Routine Patient Care Injury Prevention during Invasive Surgical, Obstetric, Dental, and Radiologic Procedures Management of Occupational Exposures to HIV in the Health Care Setting Initial Exposure Management Exposure Reporting Exposure Site Management Counseling and Triage Exposure History Evaluating the Source of Exposure Evaluating the Exposed Health Care Worker Role of HIV Testing in Preventing Occupational and Nosocomial HIV Infection Management of Infected Health Care Providers Secondary HIV Prevention: Postexposure Prophylaxis in Health Care Settings Rationale for Antiretroviral Chemoprophylaxis for Occupational Exposures to HIV Biologic Plausibility of Antiretroviral Chemoprophylaxis Efficacy of Antiretroviral Chemoprophylaxis in Animal Retroviral Infections Clinical Trials Relevant to Postexposure Chemoprophylaxis Epidemiologic and Clinical Evidence for and against the Efficacy of Postexposure Chemoprophylaxis Antiretroviral Agents for Chemoprophylaxis Choosing a Treatment Regimen Adverse Effects Associated with Postexposure Chemoprophylaxis Chemoprophylaxis in Pregnancy Indications for Chemoprophylaxis “Source Unknown” Exposures Postexposure Chemoprophylaxis for Nonoccupational HIV Exposures Timing and Duration of Chemoprophylaxis Follow-up for Occupational HIV Exposures Postexposure Medical Evaluation and HIV Testing Ongoing Monitoring for Individuals Receiving Postexposure Chemoprophylaxis Key References References Chapter 308 308 Nosocomial Herpesvirus Infections Keywords Herpes Simplex Viruses Risk of Nosocomial Transmission Mechanism of Nosocomial Transmission Prevention of Nosocomial Transmission Management of Infected or Exposed Personnel Varicella-Zoster Virus Risk of Transmission Mechanisms of Transmission Prevention of Nosocomial Transmission Investigating Nosocomial Exposure to Varicella-Zoster Virus Management of Infected or Exposed Personnel Cytomegalovirus Risk for Nosocomial Transmission Mechanisms of Nosocomial Transmission Prevention of Nosocomial Transmission Management of Infected, Exposed, and Potentially Exposed Personnel Epstein-Barr Virus Risk for Nosocomial Transmission Mechanisms of Transmission Prevention of Nosocomial Transmission Management of Infected or Exposed Personnel Human Herpesvirus 6 and Human Herpesvirus 7 Risk for Nosocomial Transmission Mechanisms of Transmission Prevention of Nosocomial Transmission Human Herpesvirus 8 Risk for Nosocomial Transmission Key References References Chapter 309 309 Infections in the Immunocompromised Host: Keywords Deficiencies in Components of Host Defenses Cellular and Humoral Immunity Granulocytes Macrophages Specific Cellular Immunity (see Chapter 6) Humoral Immunity Spleen Platelets Physical Barriers: The Integument Skin Alimentary Tract Microbial Microbiota Dysbiosis Mucosal Barrier Injury Oral Cavity Gastrointestinal Tract Respiratory Tract Other Organ Dysfunction Concomitant Infection Nutritional Status Concurrent Illnesses Origin of Fever and Infections Systemic Inflammatory Response Syndrome and Sepsis Microbiologically Defined Infections Bacteremia Bacteremia Related to Intravascular Catheters Bacteremia Related to Damaged Mucosa Other Infections Oral Cavity Respiratory Tract Including Lung Skin Vascular Devices Gastrointestinal Tract Urinary Tract Sequential Infective Events Key References References Chapter 310 310 Prophylaxis and Empirical Therapy of Infection in Cancer Patients Keywords Short View Summary Epidemiology and Risk Factors for Infections in Cancer Patients Neutropenia Mucositis Central Venous Catheters Genetic Factors Biologic Agents and Other New Drugs Oncologic Surgery Etiology Bacterial Infections Fungal Infections Viral Infections Other Pathogens Prophylaxis of Infections in Cancer Patients Antibacterial Chemoprophylaxis Antifungal Chemoprophylaxis Primary Antifungal Prophylaxis Secondary Antifungal Prophylaxis Prophylaxis Against Pneumocystis jirovecii Antiviral Prophylaxis Prophylaxis of Tuberculosis Role of Colony-Stimulating Factors in Prophylaxis Role of Immunoglobulins in Prophylaxis Other Prophylactic Measures Isolation, Food, and Lifestyle Vaccination Treatment of Infectious Complications in Cancer Patients Fever during Neutropenia Patients at Low Risk of Severe Infections Patients at High Risk of Severe Infections Duration of Antibacterial Treatment Antibacterial Treatment Modification Empirical and Preemptive Antifungal Therapy Management of a Neutropenic Patient with a Localized Infection Catheter-Related Infection Pneumonia Abdominal Infections Other Treatments Granulocyte Transfusions Use of Colony-Stimulating Factors Key References References Chapter 311 311 Risk Factors and Approaches to Infections in Transplant Recipients Keywords Host Factors of Infection Effect of Type of Transplantation Immunosuppression Infecting Microbial Agents Evaluation before Transplantation Monitoring for Infection Prophylactic Measures Prevention of Exposure to Infection Approach to Fever in the Transplant Recipient Key References References Chapter 312 312 Infections in Recipients of Hematopoietic Stem Cell Transplants Keywords Short View Summary Basic Transplantation Techniques Chemotherapy Irradiation Nonmyeloablative Transplantation Human Leukocyte Antigen Matching Prevention of Infection Clinical Syndromes Unique to the Hematopoietic Stem Cell Recipient Hemorrhagic Cystitis Veno-occlusive Disease (Sinusoidal Obstruction Syndrome) Graft-versus-Host Disease Hepatitis Pneumonia Syndromes Diarrhea Rash Osteomyelitis Patterns of Immunosuppression at Different Times after Myeloablative HSCT Preengraftment Risk Period Postengraftment Risk Period Late Risk Period Immunodeficiency after Nonmyeloablative HSCT Measures to Reduce Risks for Infection Natural History of Individual Infections after HSCT Bacterial Infections Encapsulated Bacteria Viridans-Group Streptococci Mycobacteria Intracellular Bacteria Viral Infections Herpes Simplex Virus Cytomegalovirus Varicella-Zoster Virus Adenovirus Respiratory Viruses Epstein-Barr Virus Human Herpesvirus 6 Parvovirus Fungal Infections Pneumocystis Candida Aspergillus Other Yeasts Other Molds Parasitic Infections Methods of Immune System Reconstitution after HSCT Vaccination Immunoglobulin Replacement Key References References Chapter 313 313 Infections in Solid-Organ Transplant Recipients Keywords Short View Summary Time of Occurrence of Infections after Transplantation Infections during the First 30 Days Infections between 30 and 180 Days Infections Occurring 6 Months or Later Types of Transplants and Characteristics of Infections Kidney Transplant Recipients Heart Transplant Recipients Lung and Heart-Lung Transplant Recipients Liver Transplant Recipients Abdominal Infections in Liver Transplant Recipients Pancreas Transplant Recipients Small Bowel Transplant Recipients Sites and Types of Infection Infections of the Skin and Surgical Site Infections of the Urinary Tract Infections of the Bloodstream Infections of the Chest Abdominal and Gastrointestinal Infections Hepatitis Infections of the Central Nervous System Specific Problem of Viral Infections Human Herpesvirus 6 Herpes Simplex Virus and Varicella-Zoster Virus Cytomegalovirus Respiratory Viral Infections Polyomavirus Infections and Nephropathy Human Herpesvirus 8 (Kaposi Sarcoma Herpes Virus) Lymphoproliferative Disease and Epstein-Barr Virus Infection West Nile Virus Human Immunodeficiency Virus Donor-Derived Infections Acknowledgments References Chapter 314 314 Infections in Patients with Spinal Cord Injury Keywords Short View Summary Factors That Predispose to Infection Challenges in Evaluating Patients for Infection Urinary Tract Infection Pneumonia Infection of Pressure Sores Osteomyelitis Bloodstream Infection Intra-Abdominal Infection Multiresistant Organisms in the Spinal Cord Injury Setting References Chapter 315 315 Infections in the Elderly Keywords Short View Summary Urinary Tract Infections Pneumonia Tuberculosis Pressure Sores and Skin Infections Bacteremia Infective Endocarditis Infectious Diarrhea Central Nervous System Infections Meningitis Arboviral Infections Septic Arthritis Fever and Fever of Undetermined Origin Antimicrobial Considerations Immunizations Hepatitis A and B Vaccines Yellow Fever Vaccine Rabies Vaccine Zoster Vaccine Prevention Key References References Chapter 316 316 Infections in Asplenic Patients Keywords Short View Summary Anatomy of the Spleen Function of the Spleen Regulation of Inflammation Filtration and Clearance Adaptive Immunity Innate Immunity Hematopoiesis/Hemostasis Types of Asplenia Congenital Asplenia Acquired Asplenia Acquired Hyposplenia Assessment for Splenic Function Epidemiology and Risk Factors of Sepsis in Asplenic Patients Clinical Presentation of Sepsis Secondary to Asplenia Microbial Agents Causing Postsplenectomy Sepsis Bacteria Parasites Diagnosis of Postsplenectomy Sepsis Management of Postsplenectomy Sepsis Prevention of Postsplenectomy Sepsis Prophylactic Antibiotics Vaccines Patient Education Key References References Chapter 317 317 Infections in Injection Drug Users Keywords Short View Summary Host Defenses Immune Changes Skin and Soft Tissue Infections Infection Sites Abscess Microbiology of Abscesses Abscess Diagnosis Management of Soft Tissue Infections Skin Ulcers Necrotizing Fasciitis Pyomyositis Injection Anthrax Bone and Joint Infections Epidemiology of Skeletal Infections Site of Skeletal Infection Microbiology of Skeletal Infections Infective Endocarditis Epidemiology Microbiology Pathophysiology Clinical Manifestations Diagnosis Therapy Prognosis Noncardiac Vascular Infections Septic Thrombophlebitis Mycotic Aneurysm Pulmonary Infections Pathophysiology Clinical Patterns Tuberculosis in Injection Drug Users Hepatitis Risk Factors Hepatitis B Delta Virus Hepatitis C Hepatitis A Splenic Abscess Clinical Manifestations Therapy Central Nervous System Infections Risk Factors Cerebral Mycotic Aneurysm Brain Abscess and Subdural Empyema Meningitis Spinal Epidural Abscess Tetanus and Wound Botulism Ocular Infections Endophthalmitis Human Immunodeficiency Virus Infection Epidemiology Prevention Therapy and Prognosis Sexually Transmitted Diseases Epidemiology Syphilis Key References References Chapter 318 318 Surgical Site Infections and Antimicrobial Prophylaxis Keywords Short View Summary Historical Background Principles of Surgical Site Infection Prevention Determinants and Pathophysiology Species and Sources of Wound Bacteria Virulence Factors of Major Wound Pathogens Clean Wound Infections Contaminated Wound Infections Wound Microenvironment and Operative Effects on Immunity Foreign Material and Operative Trauma to Tissue Effect of Operative Procedures on Systemic and Local Immunity Risk Factors for Surgical Site Infections Patient Factors Procedural and Proceduralist Factors Assessment of Patient Risk for Surgical Site Infection Prevention of Surgical Site Infections General Concepts Perioperative Antimicrobial Prophylaxis Antimicrobial Prophylaxis: Drug Selection and Dosing Basic Principles Drug Selection with Rising Incidence of Antibiotic-Resistant Pathogens (e.g., MRSA) MRSA-Specific Prophylaxis Special Considerations with Prophylaxis in Colorectal Surgery Dosing in Obese Patients Antimicrobial Prophylaxis: Timing of Administration and Redosing Initial Dose Timing Intraoperative Redosing Antimicrobial Prophylaxis: Duration Novel Methods of Antibiotic Prophylaxis: Local and Topical Compounds Adverse Effects of Prophylaxis Cost-Benefit of Prophylaxis Use of Surgical Prophylaxis Compliance as a Reported Measure of Health Care Quality Surgical Site Infection Surveillance Postdischarge Surgical Site Infection Surveillance Key References References Chapter 319 319 Burns Keywords Short View Summary Epidemiology Diagnosis Treatment Prevention Conclusions Key References References Chapter 320 320 Bites Keywords Short View Summary Animal Bites Management of Animal Bites Venomous Snake Bites Lip Wounds and Paronychia Human Bites Management of Human Bites Clenched-Fist Injuries Key References References Chapter 321 321 Immunization Keywords Immunologic Basis of Vaccination Determinants of Immunogenicity Live Versus Killed or Subunit Vaccines Dose Adjuvants Route of Administration Age Components of the Immune Response Mobilization of the Adaptive Immune Response Unanticipated Responses Temporal Course of the Immune Response Measurement of the Immune Response Vaccine Development General Principles of Immunization Currently Available Immunizing Agents Vaccines Anthrax Vaccine Calmette-Guérin Bacillus Vaccine Cholera Vaccine Diphtheria Toxoid Haemophilus influenzae Type b Vaccine Hepatitis A Vaccine Hepatitis B Vaccine Human Papillomavirus Vaccines Influenza Virus Vaccines–Inactivated (IIV) Live-Attenuated Influenza Vaccine Japanese Encephalitis Measles Vaccine Meningococcal Vaccines Mumps Vaccine Pertussis Vaccine Plague Vaccine Pneumococcal Polysaccharide Vaccine Pneumococcal Conjugate Vaccine Polio Vaccine Rabies Vaccine Rotavirus Vaccines Rubella Vaccine Smallpox Vaccine Tetanus Toxoid Typhoid Vaccine Varicella Vaccine Yellow Fever Vaccine Zoster Vaccine Immunoglobulin Preparations Intramuscular Immune Globulin Indications for Use of Intramuscular Immune Globulin Replacement Therapy for Antibody Deficiency Disorders. Hepatitis A Prophylaxis. Measles Prophylaxis. Specific Intramuscular Immune Globulin Preparations Hepatitis B Immune Globulin. Rabies Immune Globulin. Tetanus Immune Globulin. Varicella-Zoster Immune Globulin. Immune Globulin Intravenous Indications for Use of Immune Globulin Intravenous Specific Immune Globulins for Intravenous Use Vaccinia Immune Globulin Respiratory Syncytial Virus Immune Globulin and Palivizumab Adverse Reactions to Immune Globulin Preparations Immune Globulin Subcutaneous Rh Immune Globulin Use of Vaccines Routine Children Adolescents Adults Special Circumstances Travel Occupational Exposure Pregnancy Immunocompromised States Human Immunodeficiency Virus Postexposure Immunization Other Considerations Storage and Handling of Vaccines Assessing the Need for Immunization Immunization Records Parent and Patient Education Simultaneous Administration and Intervals between Immunizations Combination Vaccines Interrupted Schedules Reporting of Disease and Adverse Events Compensation for Vaccine Injuries Standards for Immunization Practices Methods to Improve Immunization Coverage Sources of Information Key References References Chapter 322 322 Zoonoses Keywords Short View Summary One Health Initiative Mechanisms of Transmission Factors in the Emergence of Zoonotic Diseases Prediction and Early Detection of Emerging and Reemerging Zoonotic Diseases Zoonotic Diseases Infections Associated with Wildlife Diseases Associated with Agricultural and Other Domestic Animals References Chapter 323 323 Protection of Travelers Keywords Short View Summary Epidemiology of Travel-Related Illness Immunization Update of Routine Immunizations Vaccines to Consider for All Destinations in the Developing World Hepatitis A Hepatitis B Combination Hepatitis A and Hepatitis B Vaccine Typhoid Influenza Vaccines to Consider Only for Certain Destinations Yellow Fever Meningococcus Rabies Japanese Encephalitis Polio Cholera Tick-Borne Encephalitis Spacing and Interactions of Travel-Related Vaccines Malaria Chemoprophylaxis Dengue Traveler’s Diarrhea Key Preventive Behaviors Personal Protection against Arthropods Protection against Foodborne Disease Sex Protection against Blood-Borne Disease Protection against Skin Diseases Protection against Pathogens Encountered by Swimming and Water Exposure Prevention of Tuberculosis Noninfectious Travel Problems Medical Kit and Medical Care Abroad Airline-related Morbidity Altitude Traveling Adults with Special Needs Immunocompromised Travelers and Those Infected with the Human Immunodeficiency Virus The Pregnant Traveler Key References References Chapter 324 324 Infections in Returning Travelers Keywords Short View Summary Fever Epidemiology History Detailed Travel Itinerary Chronology of Travel and Illness Exposures Immunization History Antimalarial Prophylaxis or Treatment Other Medications Ingested Physical Examination Considerations for the Common Travel-Related Febrile Illnesses Malaria Dengue Chikungunya Fever Typhoid and Paratyphoid Fever Viral Hepatitis Rickettsial Disease Leptospirosis Respiratory Illness Initial Office Approach to the Febrile Patient Diarrhea in Travelers Acute Traveler’s Diarrhea Persistent Diarrhea in the Traveler Skin Problems Eosinophilia Screening for Asymptomatic Infection Key References References Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z