Mandell, Douglas and Bennett's principles and practice of infectious diseases Volume 1

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 Untowar Part I Basic Principles In The Diagnosis And Management Of Infectious Diseases --- Section A. Microbial Pathogenesis --- A Molecular Perspective Of Microbial Pathogenicity -- Microbiome Of Local Sites And Their Unique Biology -- Prebiotics, Probiotics And Synbiotics --- Section B. Host Defense Mechanisms -- Innate (general Or Nospecific) Host Defense Mechanisms -- Adaptive Immunity: Antibodies And Immunodefiencies -- Mucosal Immunity -- Granulocytic Phagocytes And Deficiency States -- Complement And Deficiencies -- Human Genetics And Infection -- Nutrition, Immunity, And Infection -- Evaluation Of The Patient With Suspected Immunodeficiency And Other Host Defense Defects --- Section C. Epidemiology Of Infectious Disease -- Epidemiologic Principles -- Emerging And Reemerging Infectious Disease Threat -- Bioterrorism: An Overview --- Section D. Clinical Microbiology -- The Clinician And The Microbiology Laboratory --- Section E. Anti-infective Therapy --^ Principles Of Anti-infective Therapy -- Molecular Mechanisms Of Antibiotic Resistance In Bacteria -- Pharmacokinetics And Pharmacodynamics Of Anti-infective Agents Penicillins Cephalosporins -- Other ß-lactam Antibiotics -- Antibiotic Allergy -- Fusidic Acid Aminoglycosides -- Tetracyclines And Chloramphenicol Rifamycins Metronidazole -- Macrolides, Clindamycin, And Ketolides -- Glycopeptides (vancomycin And Teicoplanin), Streptogramins (quinupristin-dalfopristin), And Lipopeptides (daptomycin) -- Polymyxins (polymyxin B And Colistin) Oxazolidinones -- Sulfonamides And Trimethoprim Quinolones -- Unique Antibacterial Agents -- Urinary Tract Agents: Nitrofurantoin And Methenamine -- Topical Antibacterials -- Antimycobacterial Agents -- Drugs Active Against Fungi, Pneumocystis And Microsporidia -- Drugs For Malaria -- Drugs For Parasites Other Than Malaria -- Drugs For Helminths -- Antiviral Drugs General Principles -- Antivirals Against Influenza And Other Respiratory Viruses --^ Antivirals Against Herpes Viruses -- Antivirals Against Hepatitis Viruses -- Other Antiviral Drugs Immunomodulators -- Hyperbaric Oxygen -- Complementary And Alternative Medicines For Infectious Diseases -- Antimicrobial Management: Cost And Resistance -- Interpretation Of Clinical Trials Of Antimicrobial Agents -- Outpatient Parenteral Antimicrobial Therapy -- Tables Of Antimicrobial Agent Pharmacology ----- Part Ii Major Clinical Syndromes --- Section A. Fever -- Temperature Regulation And The Pathogenesis Of Fever -- Fever Of Unknown Origin -- The Acutely Ill Patient With Fever And Rash ---section B. Upper Respiratory Tract Infections -- The Common Cold Pharyngitis -- Acute Laryngitis -- Acute Laryngotracheobronchitis (croup) -- Otitis Externa, Otitis Media, And Mastoiditis Sinusitis Epiglottitis -- Infections Of The Oral Cavity, Neck, And Head --- Section C. Pleuropulmonary And Bronchial Infections -- Acute Bronchitis --^ Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, And Acute Exacerbations Bronchiolitis -- Acute Pneumonia -- Empyema And Pleural Effusion -- Lung Abscess -- Chronic Pneumonia -- Cystic Fibrosis --- Section D. Urinary Tract Infections -- Urinary Tract Infections --- Section E. Sepsis -- Sepsis, Severe Sepsis, And Septic Shock -- Section F. Intra-abdominal Infection -- Peritonitis And Intraperitoneal Abscesses -- Infections Of The Liver And Biliary System -- Pancreatic Infections -- Splenic Abscess Appendicitis -- Diverticulitis And Typhlitis --- Section G. Cardiovascular Infections -- Endocarditis And Intravascular Infections -- Prosthetic Valve Endocarditis -- Infections Of Non-valvular Cardiovascular Devices -- Prophylaxis Of Infective Endocarditis -- Myocarditis And Pericarditis Mediastinitis --- Section H. Central Nervous System Infections -- Approach To The Patient With Central Nervous System Infection -- Acute Meningitis -- Chronic Meningitis --^ Encephalitis, Myelitis, And Neuritis -- Brain Abscess -- Subdural Empyema, Epidural Abscess, And Intracranial Suppurative Thrombophlebitis -- Cerebrospinal Fluid Shunt Infections --- Section I. Skin And Soft Tissue Infections -- Cellulitis, Necrotizing Fasciitis And Subcutaneous Tissue Infections Myositis -- Lymphadenitis And Lymphangitis --- Section J. Gastrointestinal Infections And Food Poisoning -- Principles And Syndromes Of Enteric Infection Esophagitis -- Nausea, Vomiting, And Noninflammatory Diarrhea -- Inflammatory Enteritides -- Enteric Fever And Other Causes Of Abdominal Symptoms With Fever -- Food Poisoning -- Tropical Sprue/enteropathy --- Section K. Bone And Joint Infections -- Infectious Arthritis Osteomyelitis -- Orthopedic Implant Infections --- Section L. Diseases Of The Reproductive Organs And Sexually Transmitted Diseases -- Genital Skin And Mucous Membrane Lesions Urethritis -- Vulvovaginitis And Cervicitis -- Infections Of The Female Pelvis --^ Prostatitis, Epididymitis, And Orchitis --- Section M. Eye Infections -- Introduction To Ocular Infections -- Microbial Conjunctivitis -- Microbial Keratitis Endophthalmitis -- Infectious Causes Of Uveitis -- Periocular Infections --- Section N. Hepatitis Hepatitis --- Section O. Acquired Immunodeficiency Syndrome -- Global Perspectives On Human Immunodeficiency Virus Infection And Acquired Immunodeficiency Syndrome -- Epidemiology And Prevention Of Acquired Immunodeficiency Syndrome And Human Immunodeficiency Virus Infection -- Diagnosis Of Human Immunodeficiency Virus Infection -- The Immunology Of Human Immunodeficiency Virus Infection -- General Clinical Manifestations Of Human Immunodeficiency Virus Infection (including The Acute Retroviral Syndrome And Oral, Cutaneous, Renal, Ocular, Metabolic And Cardiac Diseases) -- Pulmonary Manifestations Of Human Immunodeficiency Virus Infection --^ Gastrointestinal And Hepatobiliary Manifestations Of Human Immunodeficiency Virus Infection -- Neurologic Diseases Caused By Human Immunodeficiency Virus-1 And Opportunistic Infections -- Human Immunodeficiency Virus Infection In Women -- Pediatric Human Immunodeficiency Virus Infection -- Antiretroviral Therapy For Human Immunodeficiency Virus Infection -- Management Of Opportunistic Infections Associated With Human Immunodeficiency Virus Infection -- Vaccines For Human Immunodeficiency Virus-1 Infection --- Section P. Miscellaneous Syndromes -- Chronic Fatigue Syndrome ---- Part Iii Infectious Diseases And Their Etiologic Agents --- Section A. Viral Diseases -- Biology Of Viruses And Viral Diseases -- Orthopoxviruses: Vaccinia (smallpox Vaccine), Variola (smallpox), Monkeypox, And Cowpox -- Other Poxviruses That Infect Humans: Parapoxviruses, Molluscum Contagiosum, And Tanapox --- Section B. Herpesviridae -- Introduction To Herpesviridae -- Herpes Simplex Virus --^ Chickenpox And Herpes Zoster (varicella-zoster Virus) Cytomegalovirus -- Epstein-barr Virus (infectious Mononucleosis) -- Human Herpesvirus Types 6 And 7 -- Kaposi's Sarcoma-associated Herpesvirus (human Herpesvirus Type 8) -- Herpes B Virus --- Section C. Adenoviridae Adenovirus --- Section D. Papovaviridae Papillomaviruses -- Jc, Bk, And Other Polyomaviruses; Progressive Multifocal Leukoencephalopathy Hepadnaviridae -- Hepatitis B Virus And Hepatitis Delta Virus Section E. Parvoviridae -- Human Parvoviruses -- Orthoreoviruses, Orbiviruses, Coltiviruses -- Seadornaviruses (colorado Tick Fever) Rotaviruses -- Alphaviruses, Including Chickungunya -- Rubella Virus (german Measles) ---- Part Iv. Flaviviruses -- Flaviviruses (yellow Fever, Dengue, Dengue Hemorrhagic Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-borne Encephalitis) -- Hepatitis C --- Section A. Coronaviridae -- Coronaviruses, Including Severe Acute Respiratory Syndrome (sars)-associated Coronavirus -- Section B. Paramyxoviridae -- Parainfluenza Viruses -- Mumps Virus -- Respiratory Syncytial Virus -- Human Metapneumovirus -- Measles Virus (rubeola) -- Zoonotic Paramyxoviruses: Hendra, Nipah, And Menangle Viruses --- Section C. Rhabdoviridae -- Vesicular Stomatitis Virus And Related Viruses -- Rabies (rhabdoviruses) --- Section D. Filoviridae -- Marburg And Ebola Virus Hemorrhagic Fevers --- Section E. Orthomyxoviridae --^ Influenza Viruses Including Avian Influenza -- Section F. Bunyaviridae --- California Encephalitis, Hantavirus Pulmonary Syndrome, And Bunyavirid Hemorrhagic Fevers --- Section G. Arenaviridae -- Lymphocytic Choriomeningitis Virus, Lassa Virus, And The South American Hemorrhagic Fevers --- Section H. Retroviridae -- Human T-cell Lymphotropic Virus Types I And Ii -- Human Immunodeficiency Viruses --- Section I. Picornaviridae -- Introduction To The Enteroviruses Poliovirus -- Coxsackieviruses, Echoviruses, And Newer Enteroviruses Parechoviruses -- Hepatitis A Virus Rhinovirus ---- Part V. Caliciviridae And Other Gastrointestinal Viruses --noroviruses And Other Caliciviruses -- Astroviruses And Picobirnaviruses --- Section A. Unclassified Viruses -- Hepatitis E Virus --- Section B. Prion Diseases -- Prions And Prion Diseases Of The Central Nervous System (transmissible Neurodegenerative Diseases) --- Section C. Chlamydial Diseases --^ Chlamydia Trachomatis (trachoma, Perinatal Infections, Lymphogranuloma Venereum, And Other Genital Infections) -- Chlamydophila (chlamydia) Psittaci (psittacosis) -- Chlamydia Pneumoniae -- Mycoplasma Pneumoniae And Atypical Pneumonia --- Section D. Mycoplasma Diseases -- Genital Mycoplasmas: Mycoplasma Genitalium, Mycoplasma Hominis, And Ureaplasma Species --- Section E. Rickettsioses, Ehrlichioses, And Anaplasmosis -- Introduction To Rickettsioses, Ehrlichioses And Anaplasmosis -- Rickettsia Rickettsii And Other Spotted Fever Group Rickettsiae (rocky Mountain Spotted Fever And Other Spotted Fevers) -- Rickettsia Akari (rickettsialpox) -- Coxiella Burnetii (q Fever) -- Rickettsia Prowazekii (epidemic Or Louse-borne Typhus) -- Rickettsia Typhi (murine Typhus) -- Orientia Tsutsugamushi -- Ehrlichia Chaffeensis And Ehrlichia Phagocytophila --- Section F. Bacterial Diseases -- Introduction To Bacteria And Bacterial Diseases --- Section G. Gram-positive Cocci --^ Staphylococcus Aureus (including Staphylococcal Toxic Shock) -- Staphylococcus Epidermidis And Other Coagulase-negative Staphylococci -- Classification Of Streptococci -- Streptococcus Pyogenes -- Nonsuppurative Poststreptococcal Sequelae: Rheumatic Fever And Glomerulonephritis -- Streptococcus Pneumonia -- Enterococcus Species, Streptococcus Bovis, And Leuconostoc Species -- Streptococcus Agalactiae (group B Streptococcus) -- Viridans Streptococci, Groups C And G Streptococci, And Gemella Morbillorum -- Streptococcus Anginosus Group --- Section H. Gram-positive Bacilli -- Corynebacterium Diphtheria -- Corynebacteria Other Than Diphtheria And Rhodococcus -- Listeria Monocytogenes -- Bacillus Anthracis (anthrax) -- Bacillus Species And Other Than Bacillus Anthracis -- Erysipelothrix Rhusiopathiae -- Whipple's Disease --- Section I. Gram-negative Cocci -- Neisseria Meningitidis -- Neisseria Gonorrhoeae -- Moraxella Catarrhalis And Other Gram-negative Cocci ---^ Section J. Gram-negative Bacilli -- Vibrio Cholerae -- Other Pathogenic Vibrios -- Campylobacter Jejuni And Related Species -- Helicobacter Pylori And Other Gastric Helicobacter Species Enterobacteriaceae -- Pseudomonas Species, Including Ps. Aeruginosa -- Stenotrophomonas Maltophilia And Burkholderia Cepacia Complex -- Burkholderia Pseudomallei And Burkholderia Mallei -- Acinetobacter Species -- Salmonella Species, Including Salmonella Typhi -- Shigella Species (bacillary Dysentery) -- Haemophilus Species (incluing H. Influenzae And Chancroid) -- Brucella Species -- Francisella Tularensis (tularemia) -- Pasteurella Species -- Yersinia Species, Including Plague -- Bordetella Pertussis -- Rat-bite Fever Streptobacillus Moniliformis And Spirillum Minus -- Legionella And Other Legionella Species Capnocytophaga -- Bartonella, Including Cat-scratch Disease -- Calymmatobacterium Granulomatis (donovanosis, Granuloma Inguinale) -- Other Gram-negative And Gram-variable Bacilli ---^ Section K. Spirochetes -- Treponema Pallidum (syphilis) -- Endemic Treponematoses -- Leptospira Species (leptospirosis) -- Relapsing Fevers Due To Borrelia Species -- Borrelia Burgdorferi (lyme Disease, Lyme Borreliosis) --- Section L. Anaerobic Bacteria -- Anaerobic Infections: General Concepts -- Clostridium Difficile -- Clostridium Tetani (tetanus) -- Clostridium Botulinum (botulism) -- Gas Gangrene And Other Clostridium-associated Diseases -- Bacteroides, Prevotella, Porphyromonas, And Fusobacterium Species (and Other Medically Important Anaerobic Gram-negative Bacilli) -- Anaerobic Cocci And Anaerobic Gram-positive Non-sporulating Bacilli --- Section M. Mycobacterial Diseases -- Mycobacterium Tuberculosis ---mycobacterium Leprae -- Mycobacterium Avium-intracellulare -- Nontuberculous Mycobacteria Other Than M. Avium-intracellulare Complex --- Section N. Higher Bacterial Diseases -- Nocardia Species -- Agents Of Actinomycosis -- Section O. Mycoses --- Introduction To Mycoses --^ Candida Species -- Aspergillus Species -- Agents Of Mucormycosis -- Sporothrix Schenckii -- Agents Of Chromomycosis -- Agents Of Mycetoma -- Cryptococcus Neoformans -- Histoplasma Capsulatum -- Blastomyces Dermatitidis -- Coccidioides Species -- Dermatophytosis And Other Superficial Mycoses -- Paracoccidioides Brasiliensis -- Uncommon Fungi And Prototheca -- Pneumocystis -- Microsporidiosis --- Section H. Protozoal Diseases -- Introduction To Protozoal Diseases -- Entamoeba Species Including Amoebiasis -- Free-living Amebas -- Plasmodium Species (malaria) -- Leishmania Species: Visceral (kala-azar), Cutaneous, And Mucocutaneous Leishmaniasis -- Biology Of Trypanosoma Species (american Trypanosomiasis, Chagas' Disease): Biology Of Trypanosomes -- Agents Of African Trypanosomiasis (sleeping Sickness) -- Toxoplasma Gondii -- Giardia Lamblia -- Trichomonas Vaginalis -- Babesia Species -- Cryptosporidium Species --^ Isospora Belli, Sarcocystis Species, Blastocystis Hominis And Cyclospora --- Section I. Diseases Due To Toxic Algae -- Human Illness Associated With Harmful Algal Blooms --- Section J. Diseases Due To Helminths -- Introduction To Helminth Infections -- Intestinal Nematodes (roundworms) -- Tissue Nematodes, Including Trichinosis, Dracunculiasis, And The Filariases -- Trematodes (schistosomes And Other Flukes) -- Cestodes (tapeworms) -- Visceral Larva Migrans And Other Unusual Helminth Infections --- Section K. Ectoparasitic Diseases -- Introduction To Ectoparasitic Diseases -- Lice (pediculosis) Scabies -- Myiasis And Tungiasis -- Mites (including Chiggers) -- Ticks (including Tick Paralysis) --- Section L. Diseases Of Unknown Etiology -- Kawasaki Disease ---- Part Iv Special Problems --- Section A. Nosocominal Infections -- Organization For Infection Control And Isolation -- Disinfection, Sterilization, And Control Of Hospital Waste --^ Infections Caused By Percutaneous Intravascular Devices -- Nosocomial Pneumonia -- Nosocomial Urinary Tract Infections -- Nosocomial Hepatitis -- Infections Transmitted By Transfusion And Transplantation -- Human Immunodeficiency Virus In Health Care Settings -- Nosocomial Herpesvirus Infections --- Section B. Infections In Special Hosts -- Infections In The Immunocompromised Host: General Principles -- Prophylaxis And Empirical Therapy Of Infection In Cancer Patients -- Risk Factors And Approaches To Infections In Transplant Recipients -- Infections In Hematopoietic Stem Cell Transplant Recipients -- Infections In Solid Organ Transplant Recipients -- Infections In Patients With Spinal Cord Injury -- Infections In The Elderly -- Infections In Asplenic Patients -- Infections In Injection Drug Users -- Postoperative Infections And Antimicrobial Prophylaxis --- Section C. Surgical And Trauma-related Infections -- Infections In Patients With Burns -- Bites --- Section D. Immunization --^ Immunization --- Section E. Zoonoses -- Zoonoses --- Section F. Protection Of Travelers -- Protection Of Travelers -- Infections In Returning Travelers [edited By] John E. Bennett, Raphael Dolin, Martin J. Blaser. Includes Bibliographical References And Index.