Le 48 Leggi Del Potere

COVER Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases Copyright Page Contributors Preface to the 9th Edition COPYRIGHT Contributors Preface to the 9th Edition I Basic Principles in the Diagnosis and Management of Infectious Diseases A Microbial Pathogenesis 1 A Molecular Perspective of Microbial Pathogenicity Attributes of Microbial Pathogens Evolution of Bacterial Pathogenicity Regulation of Bacterial Pathogenicity Close Encounters: Pathogens as Cell Biologists Identification and Characterization of Virulence Genes Molecular Microbiology at the Bedside: Pathogen Detection, Pathogen Discovery, and Genomic Profiling Dedication Key References References 2 The Human Microbiome of Local Body Sites and Their Unique Biology Defining the Human Microbiome The Human Microbiome as a Complex Ecosystem Composed of Multiple Body Site Habitats and Niches From Whence and When Do Our Microbiomes Come? 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 Pathobiont in the Vaginal Microbiome Group B Streptococcus The Human Microbiome During Pregnancy Summary and Future Directions Key References References 3 Prebiotics, Probiotics, and Synbiotics Short View Summary Issues Regarding the Complexity and Variability of Probiotics Clinical Studies of Probiotics Proposed Mechanisms of Action of Probiotics Potential Adverse Effects of Probiotic Therapy Fecal Microbiota Transplant for Infectious Conditions Other Than Clostridioides Difficile Infection Summary and Future Directions Key References References B Host Defense Mechanisms 4 Innate (General or Nonspecific) Host Defense Mechanisms Physical and Chemical Barriers to the Entry of Microorganisms Into the Body Skin Mucous Membranes Respiratory Tract Gastrointestinal Tract Genitourinary Tract Eye Innate Immune Sensing of Invading Pathogens Phagocytosis Autophagy The Inflammatory Response Cytokines and Chemotaxis Pathogen Interference With Innate Immune Responses Key References References 5 Adaptive Immunity 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 Direct Antibody-Mediated Antimicrobial Functions Antibody-Mediated Catalysis 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 Coreceptors 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 6 Cell-Mediated Defense Against Infection Short View Summary T-Cell Subsets and Phenotypic Diversity CD4 T Cells Th1 T Cells Th2 T Cells Th17 T Cells T-Regulatory Cells Helper T-Follicular Cells Plasticity of Helper T-Cell Subsets CD8 T Cells NKT Cells and T Cells With a Restricted αβ TCR Repertoire γδ T Cells T-Cell Memory T-Cell Development and Lymphoid Tissue Organization Thymic Selection of CD4 and CD8 T Cells Lymphoid Anatomy Lymph Nodes Spleen Mucosa-Associated Lymphoid Tissue T-Cell Activation Organization of the Major Histocompatibility Complex Antigen Presentation to T Lymphocytes via MHC Class I MHC Class I Structure MHC Class I Antigen-Processing Pathway Viral Interactions With the MHC Class I Antigen-Processing Pathway MHC Class I Cross-Presentation Antigen Presentation to T Lymphocytes via MHC Class II MHC Class II Structure MHC Class II Antigen-Processing Pathway CD1 and Antigen Presentation Innate Immune Recognition: Setting the Stage for T-Cell Responses Molecular Recognition of Microbial Products Toll-Like Receptors NOD-Like Receptors, RIG-I–Like Receptors, the Cyclic GMP-AMP Synthase–Stimulator of Interferon Genes Sensing Pathway, and the Inflammasome C-Type Lectin Receptors Links Between Innate Immune Recognition and Adaptive Immune Responses Dendritic Cells Microbial Pathogenesis and the Cellular Immune System Viral Infections Infections With Intracellular Bacteria and Fungi Phagosomal Pathogens Cytoplasmic Pathogens Infections With Extracellular Bacteria and Fungi Primer on Basic Immunologic Techniques Characterizing and Measuring Pathogen-Specific Immunity Key References References 7 Mucosal Immunity Short View Summary Specialization of Host Responses in Mucosal Tissues The Challenge Adaptation of Mucosal Immune Responses Microbial Communities and Development 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 Mucosal Host Response Defines Pathogenicity Good Bugs, Bad Bugs, and the Hygiene Hypothesis Mucosal Immunization Role of Mucosal Immunity: Beyond the Mucosa Conclusions Key References References 8 Granulocytic Phagocytes Neutrophils Development Emergency Granulopoiesis Mitotic and Postmitotic Cells Morphologic and Structural Characteristics Azurophilic Granules Peroxidase-Negative Granules Nucleus and Actin Cytoskeleton Organelles in the Cytoplasm Surface Receptors Homeostasis of the Circulating Neutrophil Population Distribution of Neutrophils Inflammatory Response Priming Step 1: Neutrophil Recruitment Selectin-Mediated Adhesion and Rolling β2-Integrin–Mediated Cell-Cell Interaction Tissue Migration Production of Inflammatory Mediators Role of Chemokines in Neutrophil Recruitment Step 2: Phagocytosis Opsonins Phagocytic Receptors Ingestion Step 3: Fate of the Ingested Microbe Respiratory Burst Reactive Oxygen Species NADPH Oxidase (Respiratory Burst Oxidase) Translocation of Cytosolic Components p40phox Rac2 Nonphagocyte Oxidases: The NOX Protein Family Degranulation Step 4: Resolution of the Inflammatory Response Apoptosis Proinflammatory Molecules Alter Apoptosis Microbial Pathogens Influence Neutrophil Fate Neutrophils as “Trojan Horses” Bioactive Lipid Mediators Microbicidal Mechanisms Intraphagosomal Killing of Microbes Oxygen-Dependent Killing of Microbes Oxygen-Independent Killing of Microbes Extracellular Microbicidal Activity Neutrophils and Microbial Evasion of Host Defense Microbial Responses to Neutrophils Microbial Targeting of Neutrophil Surface Molecules Survival of Microbes After Ingestion by Neutrophils Eosinophils Development and Characteristics Eosinophil Surface Receptors Eosinophil Granules Recruitment From Circulation Role in Host Defense Moderation of Type I Hypersensitivity Reactions Eosinophil-Mediated Tissue Injury Key References References 9 Complement and Deficiencies Short View Summary 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 Elimination of Pathogens Modulation of Adaptive Immune Responses Clearance of Immune Complexes and Apoptotic Cells 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 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 (MASP-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 Acknowledgment Key References References 10 Human Genetics and Infection Short View Summary Magnitude of the Host Genetic Effect Approaches Diseases Malaria Mycobacterial Diseases Viral Diseases Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome Persistent Hepatitis Other Viral Diseases Other Infectious Disease Phenotypes Specific Susceptibility and Resistance Genes Blood Groups Human Leukocyte Antigens Mannose-Binding Lectin Toll-Like Receptor Pathway Genes Evolutionary Perspective Applications Key References References 11 Nutrition, Immunity, and Infection 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 Acknowledgments Key References References 12 Evaluation of the Patient With Suspected Immunodeficiency Short View Summary 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 Syndrome) GATA2 Deficiency Complement-Mediated Immunity Acquired Immunodeficiencies Key References References C Epidemiology of Infectious Disease 13 Applied Epidemiology for the Infectious Diseases Physician What Is Epidemiology? What Can Epidemiology Tell the Infectious Disease Clinician? The Epidemiologic Triad Model: Agent, Host, and Environment The Sufficient-Component Cause Model of Epidemiology Other Methods to Characterize Infection Transmission Descriptive Epidemiology Analytic Epidemiology Experimental Studies Observational Studies Cohort Studies Case-Control Studies Cross-Sectional and Ecologic Studies Determining the Appropriate Epidemiologic Study Design Basic Biostatistics Measures of Disease Frequency Ratios, Proportions, and Rates Incidence Prevalence Measures of Association Two-by-Two Tables Prevalence Ratio and Prevalence Odds Ratio Statistical Significance P Values Confidence Intervals Disease Surveillance Classification of Surveillance Disease Prevention Disease Control: Quarantine and Isolation Outbreak Investigation Primer Outbreak Epidemiology General Key Outbreak Principles Incubation Period Epidemic Curves Transmission Modes Chains of Transmission Types of Outbreaks Foodborne Outbreaks Nosocomial Outbreaks Respiratory and Other Person-to-Person Outbreaks Sexually Transmitted Outbreaks Zoonotic and Vector-Borne Outbreaks Outbreak Investigation and Response Consequences of an Outbreak Key References References 14 Emerging and Reemerging Infectious Disease Threats Short View Summary Infectious Causes of Chronic Diseases Factors That Favor Disease Spread Antimicrobial Resistance Acute Respiratory Tract Infections Human Metapneumovirus Human Coronaviruses Human Bocaviruses Emerging Influenza Viruses Reservoirs of Influenza A Influenza A and Pandemics Novel Influenza A Viruses Influenza A(H5N1) Influenza A(H5N6) Influenza A(H7N9) Other Influenza A Virus Subtypes Variant Influenza A Infections From Swine Influenza Risk Assessment Enteric Diseases Routes of Transmission for Enteric Pathogens International Spread: Cholera in the Western Hemisphere Evolution of Enteric Pathogens Noroviruses Future Trends Vector-Borne Diseases The Aedes-Transmitted Viruses: Dengue, Zika, Yellow Fever, and Chikungunya Dengue Zika Yellow Fever Chikungunya Plasmodium vivax, Plasmodium knowlesi, and Zoonotic Malaria Tick-borne Pathogens Ebola and Marburg Hemorrhagic Fevers Conclusion: Controlling the Threats Acknowledgments Key References References 15 Bioterrorism Defining Biological Warfare, Bioterrorism, and Biocrimes History of Biological Weapons Development and Use in Warfare and Against Insurgencies Pre–World War I Biological Weapons Development and Use Development and Use of Biological Weapons During World War I Development and Use of Biological Weapons During World War II Biological Weapons in the Post–World War II Period Through the End of the Cold War Offensive Biological Weapons Programs in the United States Limiting Use of Biological Weapons: the Biological Weapons Convention Monitoring and Compliance Under the Biological Weapons Convention Civilian Research in the Soviet Union Military Activities in the Soviet Union Iraq’s Biological Weapons Program History of Biological Weapons Use to Commit Acts of Bioterrorism 20th-Century Bioterrorism Against Humans: The Rajneeshee Cult 21st-Century Bioterrorism Against Humans: The Anthrax Letters Limiting Development and Use of Biological Weapons by Terrorists Classifications of Biological Agents of Concern Formulation of the CDC List of Category A, B, and C Agents/Diseases of Bioterrorism The CDC and NIAID Biodefense and Priority Pathogen Lists in Perspective Dual Use Research of Concern, Gain-of-Function Research, and Synthetic Biology Addressing the Highest Priority Biological Agents Approval and Use of Medical Countermeasures for Priority Biological Agents Emergency Use Authorization The Animal Rule Use for Approval of Drugs, Vaccines, and Biologics Clinical Aspects of High-Consequence Bioterrorism Pathogens Variola (Smallpox) Virus Bacillus anthracis Clostridium botulinum Toxin Yersinia pestis Francisella tularensis Rickettsia prowazekii Burkholderia mallei Burkholderia pseudomallei Viral Hemorrhagic Fever Viruses Bioterrorism Incidents Clinical Provider Preparedness and Response Supplementing Health Care Provider Resources Supplementing MCMs With the Strategic National Stockpile Health Care Facility Preparedness and Response Public Health Preparedness and Response Communication Epidemiology Laboratory Preparedness and Response Surveillance Acknowledgment Key References References D Clinical Microbiology 16 The Clinician and the Microbiology Laboratory: Test Ordering, Specimen Collection, and Result Interpretation Short View Summary Microorganisms Hazardous to Laboratory Workers Taxonomy Infection Prevention and Control Bacterial, Mycobacterial, and Fungal Identification Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Antibacterial Susceptibility Testing Antimicrobial Stewardship Specimen Selection, Collection, Transportation, and Initial Processing Specific Specimen Guidelines and Initial Laboratory Processing Blood Cultures Intravenous Catheter Tips Cerebrospinal Fluid Peritoneal, Pleural, and Pericardial Fluids Bone and Joint Specimens Skin and Soft Tissue Specimens Respiratory Tract Specimens Urine Stool Vaginitis and Vaginosis Diagnostics Genital Lesions and Syphilis Diagnostics Urethritis and Cervicitis Diagnostics Helicobacter pylori Diagnostics Mycobacterium tuberculosis Diagnostics Acknowledgments Key References References E Antiinfective Therapy 17 Principles of Antiinfective Therapy Short View Summary The Antibiotic Miracle: What We Are Fighting for A Brief History of “Antibiotics” The Power of Antibiotics: What We Stand to Lose Due to Resistance The Societal Trust of Antibiotics Must Underpin Principles of Use Antibiotics Are a Societal Trust Fundamental Principles of Antibiotic Therapy 1. Proper Selection of Empirical Antibiotics Starts With an Accurate Differential Diagnosis That Includes Likely Bacterial Infection 2. Even in a Patient With a Bacterial Infection, Treat Only When Therapy Will Alter the Patient’s Clinical Course 3. Empirically Target Microbes That Cause the Diseases in the Differential Diagnosis 4. A Lower Threshold for Empirical Therapy Should Be Used in Critically Ill Patients 5. Host Factors Affect Breadth of Empirical Therapy by Altering Likely Microbial Causes of Infection 6. Pharmacokinetic-Pharmacodynamic Principles Can Influence Optimal Treatment 7. Deescalate Antibiotic Therapy Based on Microbiology Results and Clinical and Biomarker Responses 8. If Therapy Is Not Working, Consider Source Control and Alternative Diagnoses Before Blaming Resistance and Broadening Therapy 9. Distinguish New Infection From Failure of Initial Therapy 10. The Duration of Therapy Should Be Evidence Based and Short Course Whenever Possible Controversial Principles of Antibiotic Therapy The Greatly Misunderstood Dogma of Bactericidal Versus Bacteriostatic Combination Therapy: The Good, the Bad, and the Ugly The Good The Good #1: Ensuring Adequate Empirical Coverage The Good #2: Preventing Resistance Emergence The Good #3: Improving Cure Slow-growing infections/nonreplicating persisters. Exotoxin-mediated necrotizing infections. Eukaryotic infections. “The Bad”: Redundant Definitive Therapy for Typical Bacterial Infections “The Ugly”: Imperfect Data and Controversy Controversy Over Superior Outcomes With Combination Therapy for Some Infections Controversy Over Preventing Emergence of Resistance Conclusions Key References References 18 Molecular Mechanisms of Antibiotic Resistance in Bacteria Molecular Genetics of Antibiotic Resistance Plasmids Transposable Genetic Elements DNA Integration Elements Molecular Mechanisms of Antibiotic Resistance Enzymatic Inhibition of Antimicrobial Activity β-Lactamases Extended-Spectrum β-Lactamases TEM-derived β-lactamases. SHV-derived β-lactamases. CTX-M–derived extended spectrum β-lactamases. OXA-derived β-lactamases. AmpC β-lactamase enzymes. Carbapenemases. Gram-Positive Bacterial β-Lactamases 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: Glycopeptides Enterococci Staphylococci 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 Fosfomycin Metronidazole Multidrug-Resistance Mechanisms Among Bacteria Control of Antibiotic Resistance Key References References 19 Pharmacokinetics and Pharmacodynamics of Antiinfective Agents Short View Summary Pharmacokinetics Absorption Distribution Metabolism and Biotransformation Elimination Pharmacodynamics Antimicrobial Potency Pharmacodynamics Indices Methodology for Study of Pharmacodynamics Effects of Antiinfective Agents In Vitro Models Animal Models Clinical Trials Concentration-Dependent Killing Agents Time-Dependent Killing Agents Postantibiotic Effect Applied Clinical Pharmacokinetics and Pharmacodynamics Higher-Dose Extended-Interval Dosing Continuous-Infusion and Extended-Infusion Regimens Dose-Refinement Considerations Antiretroviral Pharmacodynamics Defined Exposure (PK)-Response (PD) Relationships by Class Protease inhibitors. Nonnucleoside reverse transcriptase inhibitors. Integrase strand transfer inhibitors. Entry inhibitors. Nucleoside reverse transcriptase inhibitors. Antiretroviral Therapeutic Drug Monitoring Alternative PK-PD Indices for Antiretroviral Therapy Pharmacodynamics for Other Antiviral Drugs Conclusions Key References References 20 Penicillins and β-Lactamase Inhibitors Short View Summary Penicillins Chemistry Mechanism of Action Resistance Mechanisms 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 Ureidopenicillins β-Lactamase Inhibitors and Inhibitor Combinations Clavulanic Acid Pharmacology Adverse Reactions Amoxicillin-Clavulanate Sulbactam Pharmacology Adverse Reactions Clinical Use Tazobactam Pharmacology Adverse Reactions Piperacillin-Tazobactam Clinical Use Ceftolozane-Tazobactam Avibactam Pharmacology Adverse Reactions Clinical Use Vaborbactam Pharmacology Adverse Reactions Clinical Use Key References References 21 Cephalosporins Chemistry Classification Mechanism of Action Spectrum of Activity Mechanisms of Resistance Pharmacologic Properties Adverse Reactions and Toxicities Major Clinical Uses of Cephalosporin Antibiotics First-Generation Cephalosporins Second-Generation Cephalosporins Third-Generation Cephalosporins Fourth-Generation Cephalosporins Fifth-Generation Cephalosporins (MRSA-Active Cephalosporins) Cephalosporin and β-Lactamase Inhibitor Combinations Key References References 22 Ertapenem, Imipenem, Meropenem, Doripenem, and Aztreonam Short View Summary Carbapenems Chemistry Mechanism of Action Resistance Carbapenem-Resistant Enterobacteriaceae Antibacterial Activity Pharmacology Adverse Reactions Clinical Use Monobactams Key References References 23 Antibiotic Allergy Pathophysiology Approach to a Patient With an Antibiotic Allergy Information to Be Obtained When Taking a History of Antibiotic Allergy Clinical Manifestations Immediate (Immunoglobulin E–Mediated or Pseudoallergic) Drug Reactions Nonimmediate Drug Reactions Drug Rash With Eosinophilia and Systemic Symptoms Diagnosis and Management of Antibiotic Allergy Tests for Immunoglobulin E–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 “Treating Through” Antibiotic-Associated Exanthems Drug Allergy to Specific Antimicrobial Agents β-Lactams Penicillins Epidemiology Evaluation of Penicillin Allergy as Part of Antimicrobial Stewardship 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 Antibiotic Allergy and Antimicrobial Stewardship Multiple Drug Intolerance Syndrome Key References References 24 Fusidic Acid Short View Summary Structure and Mechanism of Action Antimicrobial Activity Resistance Administration and Dosing Pharmacokinetics and Pharmacodynamics Adverse Reactions Clinical Uses Key References References 25 Aminoglycosides 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 Intraabdominal Infections Urinary Tract Infections Cystic Fibrosis Prophylaxis Spectinomycin and Gonorrhea Aminoglycosides in Orthopedic Surgery Key References References 26 Tetracyclines, Glycylcyclines, and Chloramphenicol 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 Antiinflammatory 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 Mycobacterium and Nocardia Clinical Uses Skin and Skin Structure Infections Intraabdominal Infections Respiratory Tract Infections Other Uses Mechanism of Resistance Adverse Reactions Gastrointestinal Side Effects Hepatotoxicity and Pancreatitis Other Side Effects Increased Mortality Drug Interactions New Drug Approvals: Eravacycline and Omadacycline Chloramphenicol Structure and Mechanism of Action Pharmacology Administration and Dosage 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 27 Rifamycins Short View Summary Structure and Mechanism of Action Mechanisms of Resistance Shared Properties of the Rifamycins Rifampin Pharmacokinetics Adverse Reactions Antimicrobial Activity Rifabutin Pharmacokinetics Adverse Reactions Antimicrobial Activity Rifapentine Pharmacokinetics Adverse Effects Antimicrobial Activity Rifaximin Pharmacokinetics Adverse Effects Antimicrobial Activity 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 Staphylococcus aureus and Rifampin Prosthetic Joint Infections Osteomyelitis Central Nervous System Infections Infections Caused by Other Bacteria Streptococcus pneumoniae Enterococci Legionella Rhodococcus Multidrug-Resistant Gram-Negative Bacilli Brucella Bartonella Fungal Infections Second