BOOK
Fungal Infections, An Issue of Infectious Disease Clinics of North America, E-Book
Luis Ostrosky-Zeichner | Jack Sobel
(2016)
Additional Information
Book Details
Abstract
There have been major advances in new therapies, diagnostic tools, and strategies for treatment and prevention of fungal infections. Despite these encouraging developments, large numbers of patients are at risk for infectious diseases, and the epidemiology of invasive mycoses continues to emerge. The diagnosis of these infections remains difficult, and treatment outcomes in highly immunosuppressed patients remain poor. Thus, this issue is devoted to state-of-the-art updates on fungal infections by internationally recognized authorities in this field. Some topics covered are Antifungal agents; State-of-the-art culture, identification, and resistance testing of fungal pathogens; Non-culture diagnostics in fungal disease; Contemporary strategies in the prevention and management of fungal infections; Invasive candidiasis; Invasive aspergillosis; Mucormycoses; and Cryptococcosis to name a few.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Fungal Infections\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| CONSULTING EDITOR | iii | ||
| EDITORS | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Fungal Infections\r | vii | ||
| The Global Burden of Fungal Diseases\r | vii | ||
| Update from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance\r | vii | ||
| Nonculture Diagnostics in Fungal Disease\r | vii | ||
| Antifungal Agents: Spectrum of Activity, Pharmacology, and Clinical Indications\r | viii | ||
| Basic Genetics and Immunology of Candida Infections\r | viii | ||
| Invasive Candidiasis\r | viii | ||
| Invasive Aspergillosis: Current Strategies for Diagnosis and Management\r | viii | ||
| Mucormycoses\r | ix | ||
| Dematiaceous Molds\r | ix | ||
| Cryptococcosis\r | ix | ||
| Histoplasmosis\r | ix | ||
| Coccidioidomycosis\r | x | ||
| Blastomycosis\r | x | ||
| Contemporary Strategies in the Prevention and Management of Fungal Infections\r | x | ||
| Approach to the Solid Organ Transplant Patient with Suspected Fungal Infection\r | xi | ||
| INFECTIOUS DISEASE CLINICS\rOF NORTH AMERICA\r | xii | ||
| FORTHCOMING ISSUES | xii | ||
| June 2016 | xii | ||
| September 2016 | xii | ||
| December 2016 | xii | ||
| RECENT ISSUES | xii | ||
| December 2015 | xii | ||
| September 2015 | xii | ||
| June 2015 | xii | ||
| Preface:Fungal \rInfections | xiii | ||
| The Global Burden of Fungal Diseases | 1 | ||
| Key points | 1 | ||
| INTRODUCTION | 1 | ||
| YEASTS | 2 | ||
| Candida | 2 | ||
| Cryptococcus | 3 | ||
| OTHER FUNGUS | 4 | ||
| Pneumocystis jirovecii | 4 | ||
| MOLDS | 4 | ||
| Aspergillus | 4 | ||
| Mucormycetes | 5 | ||
| Scedosporium | 5 | ||
| Fusarium | 5 | ||
| ENDEMIC MOLDS | 5 | ||
| Histoplasma capsulatum | 5 | ||
| Coccidioides immitis and Coccidioides posadasii | 5 | ||
| Paracoccidioides brasiliensis | 6 | ||
| Blastomyces dermatitidis | 6 | ||
| Talaromyces (Penicillium) marneffei | 6 | ||
| OTHER FUNGAL ORGANISMS | 6 | ||
| Organisms Causing Eumycetoma | 6 | ||
| Emerging Pathogens | 7 | ||
| SUMMARY | 7 | ||
| REFERENCES | 8 | ||
| Update from the Laboratory | 13 | ||
| Key points | 13 | ||
| INTRODUCTION | 13 | ||
| FUNGAL IDENTIFICATION IN THE CLINICAL SETTING | 14 | ||
| Identification by Morphologic/Phenotypic Characteristics and DNA Sequence Analysis | 14 | ||
| Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry | 15 | ||
| IDENTIFICATION OF FUNGI WITH DIRECT SPECIMENS | 16 | ||
| T2 Magnetic Resonance Technology | 17 | ||
| Cryptococcal Antigen Lateral Flow Assay | 17 | ||
| ANTIFUNGAL SUSCEPTIBILITY TESTING | 18 | ||
| Clinical and Laboratory Standards Institute and European Union Committee on Antimicrobial Susceptibility Testing Reference ... | 18 | ||
| Commercially Available Antifungal Susceptibility Assays | 22 | ||
| TRENDS IN ANTIFUNGAL RESISTANCE | 23 | ||
| Echinocandin Resistance in Candida glabrata | 23 | ||
| Azole Resistance in Aspergillus fumigatus | 24 | ||
| SUMMARY | 25 | ||
| REFERENCES | 25 | ||
| Nonculture Diagnostics in Fungal Disease | 37 | ||
| Key points | 37 | ||
| INTRODUCTION | 37 | ||
| ANTIBODY DETECTION | 39 | ||
| ANTIGEN DETECTION | 39 | ||
| (1, 3)-β-D-Glucan | 39 | ||
| Aspergillus Galactomannan | 39 | ||
| Antigen Detection for Dimorphic Fungi | 42 | ||
| Cryptococcal Antigen | 42 | ||
| Histology and Special Stains | 43 | ||
| NUCLEIC ACID DETECTION TECHNIQUES | 43 | ||
| Pan-Fungal Approaches | 44 | ||
| Genus/Species-Specific Approaches | 44 | ||
| Detection of Molecular Markers of Resistance | 45 | ||
| SUMMARY | 46 | ||
| REFERENCES | 46 | ||
| Antifungal Agents | 51 | ||
| Key points | 51 | ||
| INTRODUCTION: THE EVOLUTION OF ANTIFUNGAL DRUG THERAPY | 51 | ||
| PHARMACOLOGIC CONSIDERATIONS | 53 | ||
| POLYENES | 53 | ||
| Spectrum of Activity and Resistance | 53 | ||
| Pharmacology | 53 | ||
| Clinical Indications | 58 | ||
| Toxicities | 58 | ||
| Drug–Drug Interactions | 59 | ||
| FLUCYTOSINE | 59 | ||
| Spectrum of Activity and Resistance | 59 | ||
| Pharmacology | 60 | ||
| Clinical Indications | 60 | ||
| Toxicities | 60 | ||
| Drug–Drug Interactions | 60 | ||
| AZOLES | 60 | ||
| Spectrum of Activity and Resistance | 61 | ||
| Fluconazole | 61 | ||
| Itraconazole | 61 | ||
| Voriconazole | 61 | ||
| Posaconazole | 61 | ||
| Isavuconazole | 62 | ||
| Resistance | 62 | ||
| Pharmacology | 62 | ||
| Fluconazole | 62 | ||
| Itraconazole | 62 | ||
| Voriconazole | 63 | ||
| Posaconazole | 64 | ||
| Isavuconazole | 64 | ||
| Clinical Indications | 65 | ||
| Fluconazole | 65 | ||
| Itraconazole | 65 | ||
| Voriconazole | 66 | ||
| Posaconazole | 67 | ||
| Isavuconazole | 67 | ||
| Toxicities | 67 | ||
| Drug–drug interactions | 67 | ||
| ECHINOCANDINS | 68 | ||
| Spectrum of Activity and Resistance | 68 | ||
| Pharmacology | 68 | ||
| Clinical Indications | 69 | ||
| Toxicities | 69 | ||
| Drug–Drug Interactions | 69 | ||
| REFERENCES | 70 | ||
| Basic Genetics and Immunology of Candida Infections | 85 | ||
| Key points | 85 | ||
| INTRODUCTION | 85 | ||
| MONOGENIC INHERITANCE OF CANDIDA INFECTIONS | 86 | ||
| Isolated Chronic Mucocutaneous Candidiasis | 86 | ||
| Syndromic Chronic Mucocutaneous Candidiasis | 87 | ||
| Chronic Mucocutaneous Candidiasis Associated with Primary Immunodeficiencies | 92 | ||
| Invasive Candida Infections | 92 | ||
| POLYGENIC INHERITANCE OF CANDIDA INFECTIONS | 93 | ||
| SUMMARY | 97 | ||
| REFERENCES | 97 | ||
| Invasive Candidiasis | 103 | ||
| Key points | 103 | ||
| INTRODUCTION | 103 | ||
| EPIDEMIOLOGY | 103 | ||
| PATHOGENESIS | 105 | ||
| DIAGNOSIS | 105 | ||
| ANTIFUNGAL SUSCEPTIBILITY TESTING | 106 | ||
| CLINICAL MANIFESTATIONS | 108 | ||
| Candidemia | 108 | ||
| Neonatal Candidiasis | 108 | ||
| Acute Disseminated Candidiasis | 109 | ||
| Endovascular Infection | 109 | ||
| Osteomyelitis and Arthritis | 109 | ||
| Endophthalmitis | 110 | ||
| Chronic Disseminated Candidiasis (Hepatosplenic Candidiasis) | 110 | ||
| Other | 110 | ||
| TREATMENT | 111 | ||
| General Principles of Therapy | 111 | ||
| Echinocandins | 111 | ||
| Triazoles | 114 | ||
| Amphotericin B Formulations | 115 | ||
| EMPIRICAL THERAPY | 115 | ||
| PREVENTION | 115 | ||
| REFERENCES | 116 | ||
| Invasive Aspergillosis | 125 | ||
| Key points | 125 | ||
| INTRODUCTION | 125 | ||
| MYCOLOGY AND EPIDEMIOLOGY | 126 | ||
| HOST SUSCEPTIBILITY | 128 | ||
| CLINICAL MANIFESTATIONS | 129 | ||
| NONINVASIVE DISEASE | 129 | ||
| Aspergilloma | 129 | ||
| Allergic Bronchopulmonary Aspergillosis | 129 | ||
| Chronic Forms of Pulmonary Aspergillosis | 130 | ||
| INVASIVE DISEASE | 130 | ||
| Invasive Pulmonary Aspergillosis | 130 | ||
| Tracheobronchial Aspergillosis | 131 | ||
| Extrapulmonary Involvement | 131 | ||
| Aspergillosis rhinosinusitis | 131 | ||
| Ocular Aspergillosis | 131 | ||
| Aspergillus osteomyelitis | 132 | ||
| Central Nervous System Aspergillosis | 132 | ||
| DIAGNOSIS | 132 | ||
| TREATMENT | 133 | ||
| Triazoles | 133 | ||
| Voriconazole | 134 | ||
| Posaconazole | 134 | ||
| Itraconazole | 135 | ||
| Isavuconazole | 135 | ||
| Echinocandins | 135 | ||
| Amphotericin B | 135 | ||
| Combination Therapy | 136 | ||
| ANTIFUNGAL RESISTANCE | 136 | ||
| BREAKTHROUGH INFECTIONS | 137 | ||
| SUMMARY | 137 | ||
| REFERENCES | 137 | ||
| Mucormycoses | 143 | ||
| Key points | 143 | ||
| INTRODUCTION | 143 | ||
| EPIDEMIOLOGY | 144 | ||
| PATHOGENESIS | 145 | ||
| CLINICAL MANIFESTATIONS | 147 | ||
| DIAGNOSIS | 149 | ||
| ANTIFUNGAL TREATMENT | 151 | ||
| ADJUNCTIVE MANAGEMENT | 152 | ||
| SUMMARY AND FUTURE DIRECTIONS | 153 | ||
| ACKNOWLEDGMENTS | 153 | ||
| REFERENCES | 154 | ||
| Dematiaceous Molds | 165 | ||
| Key points | 165 | ||
| INTRODUCTION | 165 | ||
| MYCOLOGY | 166 | ||
| DIAGNOSIS | 167 | ||
| PATHOGENESIS | 167 | ||
| IN VITRO SUSCEPTIBILITY | 167 | ||
| CLINICAL SYNDROMES AND THERAPY | 168 | ||
| Superficial Infections | 169 | ||
| Onychomycosis | 169 | ||
| Subcutaneous lesions | 171 | ||
| Keratitis | 171 | ||
| Allergic Disease | 171 | ||
| Fungal sinusitis | 171 | ||
| Allergic bronchopulmonary mycosis | 172 | ||
| Pneumonia | 172 | ||
| Brain Abscess | 172 | ||
| Disseminated Infection | 173 | ||
| Miscellaneous | 174 | ||
| SUMMARY | 174 | ||
| REFERENCES | 174 | ||
| Cryptococcosis | 179 | ||
| Key points | 179 | ||
| INTRODUCTION | 179 | ||
| THE PATHOGENS: CRYPTOCOCCUS NEOFORMANS AND CRYPTOCOCCUS GATTII | 180 | ||
| EPIDEMIOLOGY AND RISK FACTORS | 182 | ||
| Pathogenesis and Host Immunity | 182 | ||
| CLINICAL MANIFESTATIONS | 184 | ||
| Pulmonary Infection | 184 | ||
| Central Nervous System Infection | 185 | ||
| Skin Infection | 186 | ||
| Prostate Infection | 186 | ||
| Eye Infection | 186 | ||
| Infection at Other Body Sites | 186 | ||
| Immune Reconstitution Inflammatory Syndrome | 187 | ||
| LABORATORY DIAGNOSIS | 188 | ||
| Direct Examination/India Ink | 188 | ||
| Culture and Identification | 189 | ||
| Cytology and Histopathology | 189 | ||
| Serology | 190 | ||
| TREATMENT | 190 | ||
| Basic Principles | 190 | ||
| Timing of Antiretroviral Therapy | 192 | ||
| Organ Transplant Recipients | 193 | ||
| Non–HIV-Infected, Nontransplant Patients | 193 | ||
| Management of Intracranial Pressure | 193 | ||
| Persistent and Relapsed Infection | 194 | ||
| Nonmeningeal Disease | 194 | ||
| Screening and Prevention | 195 | ||
| REFERENCES | 196 | ||
| Histoplasmosis | 207 | ||
| Key points | 207 | ||
| INTRODUCTION | 207 | ||
| EPIDEMIOLOGY | 208 | ||
| PATHOGENESIS | 208 | ||
| CLINICAL | 210 | ||
| Acute Pulmonary Histoplasmosis | 210 | ||
| Subacute Pulmonary Histoplasmosis | 210 | ||
| Chronic Pulmonary Histoplasmosis | 210 | ||
| Pulmonary Nodules | 210 | ||
| Mediastinal Lymphadenopathy (or Mediastinal Adenitis) | 212 | ||
| Mediastinal Granuloma | 214 | ||
| Mediastinal Fibrosis (or Fibrosing Mediastinitis) | 214 | ||
| Histoplasmoma | 214 | ||
| Broncholithiasis | 215 | ||
| Presumed Ocular Histoplasmosis | 215 | ||
| Disseminated Histoplasmosis | 215 | ||
| DIAGNOSIS | 215 | ||
| Pathology | 215 | ||
| Culture | 217 | ||
| Antigen Testing | 217 | ||
| Antibody Testing | 219 | ||
| Molecular | 219 | ||
| TREATMENT | 219 | ||
| Manifestations That Are Usually or Always Treated | 220 | ||
| Acute pulmonary histoplasmosis (usually treated) | 220 | ||
| Chronic pulmonary histoplasmosis (always treated) | 220 | ||
| Progressive disseminated histoplasmosis (always treated) | 220 | ||
| Manifestations That Usually Are Not Treated | 221 | ||
| Subacute pulmonary histoplasmosis | 221 | ||
| Pulmonary nodules | 221 | ||
| Mediastinal lymphadenopathy (or mediastinal adenitis) | 221 | ||
| Mediastinal granuloma | 222 | ||
| Mediastinal fibrosis | 222 | ||
| Presumed ocular histoplasmosis | 222 | ||
| REFERENCES | 222 | ||
| Coccidioidomycosis | 229 | ||
| Key points | 229 | ||
| INTRODUCTION | 229 | ||
| EPIDEMIOLOGY | 230 | ||
| DIAGNOSTIC TESTING | 230 | ||
| CLINICAL MANIFESTATIONS AND MANAGEMENT | 232 | ||
| Primary Pulmonary Infection | 232 | ||
| Diffuse Pneumonia | 233 | ||
| Residual Nodule, Cavity, and Chronic Infiltrates | 234 | ||
| Extrapulmonary Disease | 235 | ||
| Coccidioidal Meningitis | 235 | ||
| Coccidioidomycosis in Immunocompromised Patients | 236 | ||
| ANTIFUNGAL THERAPY | 237 | ||
| Amphotericin | 237 | ||
| Azoles | 238 | ||
| Newer Triazoles | 239 | ||
| Echinocandins | 240 | ||
| Interferon Gamma Therapy | 240 | ||
| Future Therapies | 240 | ||
| SUMMARY | 241 | ||
| REFERENCES | 241 | ||
| Blastomycosis | 247 | ||
| Key points | 247 | ||
| INTRODUCTION | 247 | ||
| EPIDEMIOLOGY | 248 | ||
| PATHOGENESIS | 249 | ||
| CLINICAL MANIFESTATIONS | 250 | ||
| Acute Pulmonary Blastomycosis | 250 | ||
| Chronic Pulmonary Blastomycosis | 251 | ||
| Extrapulmonary Blastomycosis | 252 | ||
| Skin manifestations | 252 | ||
| Osteoarticular structures | 254 | ||
| Genitourinary tract | 254 | ||
| Central nervous system | 255 | ||
| BLASTOMYCOSIS IN SPECIAL POPULATIONS | 255 | ||
| Immunocompromised Patients | 255 | ||
| Human immunodeficiency virus/AIDS | 255 | ||
| Transplant recipients | 255 | ||
| Tumor necrosis factor–alpha inhibitor therapy | 255 | ||
| Pregnancy | 256 | ||
| Children | 256 | ||
| DIAGNOSIS | 256 | ||
| Culture | 256 | ||
| Histopathology | 256 | ||
| Antigen Detection | 256 | ||
| Serology | 257 | ||
| Nucleic Acid Testing | 257 | ||
| TREATMENT | 257 | ||
| Mild to Moderate Pulmonary or Disseminated Blastomycosis | 257 | ||
| Moderately Severe to Severe Pulmonary or Disseminated Blastomycosis | 257 | ||
| Central Nervous System Blastomycosis | 259 | ||
| Immunosuppressed Patients | 259 | ||
| Pregnant Women and Children | 260 | ||
| OUTCOMES | 260 | ||
| REFERENCES | 260 | ||
| Contemporary Strategies in the Prevention and Management of Fungal Infections | 265 | ||
| Key points | 265 | ||
| INTRODUCTION | 265 | ||
| CONTEMPORARY STRATEGIES IN THE PREVENTION AND MANAGEMENT OF INVASIVE CANDIDIASIS | 266 | ||
| Pharmacologic Prevention of Invasive Candidiasis | 266 | ||
| Management of Invasive Candidiasis: Fever or Diagnostic-Driven Approach | 266 | ||
| Management of Invasive Candidiasis: Targeted Treatment | 267 | ||
| CONTEMPORARY STRATEGIES IN THE PREVENTION AND MANAGEMENT OF INVASIVE ASPERGILLOSIS | 268 | ||
| Pharmacologic Prevention of Invasive Aspergillosis | 268 | ||
| Management of Invasive Aspergillosis: Fever or Diagnostic-Driven Approach | 268 | ||
| Management of Invasive Aspergillosis: Targeted Treatment | 268 | ||
| CONTEMPORARY STRATEGIES IN THE PREVENTION AND MANAGEMENT OF MUCORMYCOSIS | 269 | ||
| Pharmacologic Prevention of Mucormycosis | 269 | ||
| Management of Mucormycosis: Targeted Treatment | 269 | ||
| REFERENCES | 271 | ||
| Approach to the Solid Organ Transplant Patient with Suspected Fungal Infection | 277 | ||
| Key points | 277 | ||
| INTRODUCTION | 277 | ||
| EPIDEMIOLOGY OF INVASIVE FUNGAL INFECTIONS AFTER SOLID ORGAN TRANSPLANTATION | 278 | ||
| Timing of Invasive Fungal Infections After Solid Organ Transplant | 278 | ||
| Risk Factors for Invasive Fungal Infections Following Solid Organ Transplant | 279 | ||
| RECOGNITION OF INVASIVE FUNGAL INFECTIONS BY CLINICAL SYNDROME | 281 | ||
| Pulmonary Fungal Infections | 281 | ||
| Pulmonary nodules or masses | 281 | ||
| Pulmonary ground-glass opacities | 282 | ||
| Diagnostic evaluation for pulmonary fungal infections | 283 | ||
| Central Nervous System Fungal Infections | 283 | ||
| Meningitis | 283 | ||
| Brain abscess | 284 | ||
| Frontal lobe lesions with sinus disease | 285 | ||
| Cutaneous Manifestations of Invasive Fungal Infections | 285 | ||
| Aspergillosis | 285 | ||
| Cryptococcosis | 286 | ||
| Mucormycosis | 286 | ||
| Phaeohyphomycosis | 287 | ||
| Invasive Fungal Infections Causing a Sepsis Syndrome | 287 | ||
| EMPIRIC ANTIFUNGAL THERAPY FOR SUSPECTED INVASIVE FUNGAL INFECTIONS | 287 | ||
| SUMMARY | 288 | ||
| REFERENCES | 288 | ||
| Index | 297 |