Fungal Infections in the Immunocompromised Patient (Infectious Disease and Therapy Book 34)

Unlike any other source on the subject, this reference provides an up-to-date account of fungal syndromes in immunocompromised patients and provides expert descriptions of their clinical manifestations and settings in which they cause illness-covering the pros and cons of current and emerging diagnostic measures, techniques to incorporate new diagnostic tools and treatments into established clinical practices, and the most recent therapeutic strategies in patient care. Doody Review Services Reviewer: Andre C. Kalil, MD(University of Nebraska Medical Center) Description: This book provides a comprehensive review of fungal infections in immunocompromised patients. It includes the most common causes of immunosuppression, such as solid organ transplantation, bone marrow transplantation, cancer, Human Immunodeficiency Virus, and being in the intensive care unit. Purpose: This book aims to provide an up-to-date overview of fungal infections in immunocompromised patients, including risk factors, shifts in incidence, and the challenges of the diagnosis and treatment of these infections. Both editors are renowned experts in the field of fungal infections involving bone marrow transplantation and oncology patients. Audience: As expected, the authors try to direct this book to a wide variety of clinicians, microbiologists, and researchers, but this extensive review of fungal infections is mostly of interest to transplant, infectious disease, oncology, and critical care specialists. Nonetheless, for the general practitioner who sees immunocompromised patients and does not have access to specialists, this book may be an invaluable help. Features: The book achieves the very difficult task of approaching most important aspects of fungal infections in immunocompromised patients. Most chapters use several tables to present important concepts. However, pictures of various microorganisms are in black and white and suffer from poor resolution. Summary tables embedded in the text highlighting the main features of each chapter would be beneficial for the reader. Last, inherent to books in general due to the time that it takes from conception to final publication, the most recent clinical trial results on newer antifungal drugs such as micafungin, anidulafungin, and pozaconazole are not included in this book. Assessment: This is an excellent and meticulous book on fungal infections in the immunocompromised patient. It will surely aid clinicians involved in the care of these patients. Front cover......Page 1 Preface......Page 8 Contents......Page 12 Contributors......Page 20 II. INNATE IMMUNITY......Page 24 B. Soluble Components......Page 25 C. Recognition of the Pathogen Through Pattern-Recognition Receptors......Page 26 E. Phagocytes......Page 29 A. Humoral Immunity......Page 41 B. Cell-mediated Immunity......Page 42 IV. HOST DEFENSES AGAINST THE MOST COMMON FUNGI IN IMMUNOCOMPROMISED HOSTS......Page 49 B. Yeasts......Page 53 C. Dimorphic Fungi......Page 55 D. Dermatophytosis and Other Cutaneous Fungal Infections......Page 56 REFERENCES......Page 57 I. INTRODUCTION......Page 68 II. INVASIVE FUNGAL INFECTION IN SOLID ORGAN-TRANSPLANT PATIENTS......Page 70 III. RISK OF INVASIVE FUNGAL INFECTION IN THE SOLID ORGAN-TRANSPLANT RECIPIENT......Page 71 B. Environmental Exposures of Importance in the Pathogenesis of Fungal Infection in the Solid Organ-Transplant Recipient......Page 72 C. Net State of Immunosuppression in the Organ-Transplant Recipient......Page 74 IV. TEMPORAL ASPECTS OF FUNGAL INFECTION IN THE SOLID ORGAN-TRANSPLANT RECIPIENT......Page 75 A. Fungal Infection in the First Month Post-transplant......Page 76 B. Fungal Infection 1 to 6 Months Post-transplant......Page 77 V. FUNGAL INFECTIONS OF IMPORTANCE IN THE ORGAN-TRANSPLANT RECIPIENT A. Candidiasis......Page 78 B. Aspergillosis......Page 80 C. Cryptococcosis......Page 84 D. Zygomycosis (Mucormycosis)......Page 86 VI. PRINCIPLES OF ANTIFUNGAL THERAPY IN SOLID ORGAN-TRANSPLANT RECIPIENTS A. Modes of Therapy......Page 88 B. Drug Interactions......Page 89 C. Antifungal Agents......Page 93 REFERENCES......Page 94 II. FUNGAL INFECTIONS: OVERALL INCIDENCE AND RISKS......Page 98 A. Candida Species......Page 100 B. Aspergillus Species......Page 103 C. Other Fungi......Page 106 III. CONCLUSION......Page 109 REFERENCES......Page 110 II. EPIDEMIOLOGY OF INVASIVE FUNGAL INFECTION OBSERVED AT AUTOPSY......Page 120 III. SUPERFICIAL AND INVASIVE CANDIDIASIS......Page 124 IV. INVASIVE FILAMENTOUS FUNGAL INFECTION......Page 128 V. COLONIZATION......Page 130 VI. MYELOSUPPRESSION AND IMMUNOSUPPRESSION......Page 131 VII. CYTOTOXIC THERAPY-INDUCED MUCOSAL INJURY AND INVASIVE FUNGAL INFECTION......Page 136 REFERENCES......Page 137 II. SPECIFIC FUNGAL INFECTIONS A. Pneumocystis jiroveci......Page 152 C. Candidiasis......Page 155 D. Histoplasmosis......Page 156 E. Coccidioidomycosis......Page 157 G. Blastomycosis......Page 158 H. Mycoses Caused by Molds......Page 159 K. Agents of Phaeohyphomycosis (Cladophialophora,......Page 160 B. Immune Reconstitution Illness......Page 161 C. Discontinuation of Prophylatic Medications......Page 162 REFERENCES......Page 163 A. Candida albicans......Page 172 III. THE MICROBIOLOGY, INCIDENCE, MORBIDITY, AND MORTALITY OF CANDIDA INFECTION......Page 173 A. The Changing Microbiological Picture of Candida Infections......Page 174 B. Mortality of Candida Infection......Page 175 IV. CLINICAL ASPECTS OF CANDIDA INFECTION A. Sources of Candida in the Critical Care Patient......Page 176 C. Colonization as a Major Risk Factor for Subsequent......Page 178 V. WHO SHOULD RECEIVE ANTIFUNGAL PROPHYLAXIS IN THE ICU?......Page 180 VI. SPECIAL POPULATIONS AT RISK OF CANDIDA INFECTIONS AND POSSIBLY MERITING PROPHYLAXIS A. Liver Transplantation......Page 183 C. Postoperative Intra-Abdominal Infection......Page 184 B. Is Fluconazole Sufficient for Empiric Antifungal Therapy?......Page 185 C. Duration of Therapy......Page 186 VIII. CATHETER MANAGEMENT IN CANDIDEMIC PATIENTS......Page 187 IX. DESCRIPTIONS OF SPECIFIC AGENTS A. Imidazoles......Page 188 B. Voriconazole......Page 189 C. Amphotericin B......Page 190 D. Lipid Formulations of Amphotericin B......Page 191 E. The Echinocandins......Page 192 X. RECOMMENDATIONS FOR THERAPY—A CARE PATH......Page 193 XI. OTHER SITES OF CANDIDA INFECTIONS A. Candida Endophthalmitis......Page 194 D. Peritonitis and Intra-Abdominal Abscess......Page 195 F. Pneumonia......Page 196 REFERENCES......Page 197 I. INTRODUCTION......Page 208 II. SPECIFIC FUNGAL INFECTIONS A. Candida Species......Page 210 B. Aspergillus Species......Page 214 C. Other Fungal Infections......Page 215 REFERENCES......Page 216 I. UNEXPLAINED FEVER......Page 222 II. BRONCHOPNEUMONIA A. Aspergillus and Aspergillus-like Pulmonary Fungal Infections......Page 224 B. Other Pathogens......Page 227 III. SKIN LESIONS......Page 228 IV. SINUSITIS AND CENTRAL NERVOUS SYSTEM DISEASE......Page 230 V. DISSEMINATED DISEASE AND MISCELLANEOUS ISSUES......Page 232 REFERENCES......Page 233 II. THE PATHOGEN......Page 238 III. EPIDEMIOLOGY......Page 239 V. SYNDROMES A. Disseminated candidiasis......Page 241 B. Local Infections......Page 246 VI. DIAGNOSIS A. Direct Microscopy......Page 254 C. Identification Methods......Page 255 VII. THERAPY A. Disseminated Candidiasis......Page 256 B. Local Infections......Page 260 VIII. PREVENTION......Page 262 C. Antifungal Chemoprophylaxis......Page 263 REFERENCES......Page 265 I. ETIOLOGY AND EPIDEMIOLOGY......Page 280 II. SYNDROMES A. Invasive Aspergillosis......Page 281 C. Disseminated Aspergillosis......Page 283 F. Cutaneous Aspergillosis......Page 284 A. Microscopy, Culture, and Histopathology......Page 285 B. Antibodies......Page 287 C. Antigens......Page 288 F. Nucleic Acid-Based Diagnosis in Clinical Materials......Page 289 I. Target Genes......Page 290 K. Real-Time PCR......Page 291 IV. THERAPY A. Prevention......Page 292 C. Amphotericin B Formulations......Page 293 D. Itraconazole......Page 294 E. Voriconazole......Page 295 G. Caspofungin......Page 296 H. Other Echinocandins: Micafungin and Anidulafungin......Page 297 I. Combination Therapy......Page 298 K. Immunomodulatory Therapy......Page 299 REFERENCES......Page 301 A. Histoplasmosis......Page 318 B. Blastomycosis......Page 322 C. Coccidioidomycosis......Page 325 D. Paracoccidioidomycosis......Page 327 E. Penicilliosis......Page 328 II. SUMMARY......Page 329 REFERENCES......Page 330 II. EMERGING YEASTS A. Trichosporon species......Page 334 B. Wangiella dermatitidis......Page 336 C. Malassezia species......Page 337 D. Pichia species......Page 338 A. Fusarium species......Page 339 C. Scedosporium species......Page 342 D. Paecilomyces species......Page 344 E. Trichoderma species......Page 345 F. Zygomycetes......Page 347 IV. DEMATIACEOUS MOLDS......Page 348 V. CRYPTOCOCCUS SPP.......Page 350 VI. CONCLUSION......Page 352 REFERENCES......Page 353 I. INTRODUCTION......Page 364 II. CLINICAL RECOGNITION OF FUNGAL INFECTION......Page 366 IV. CONVENTIONAL METHODS FOR THE LABORATORY DIAGNOSIS OF FUNGAL INFECTIONS......Page 367 A. Specimen Collection and Processing......Page 369 B. Direct Microscopy......Page 373 D. Culture......Page 385 E. Identifying Characteristics of Fungi......Page 393 F. Role of Surveillance Cultures......Page 395 V. ANTIFUNGAL SUSCEPTIBILITY TESTING......Page 396 REFERENCES......Page 399 I. INTRODUCTION......Page 406 A. Antibody Detection......Page 407 B. Antigen Detection......Page 409 III. SERODIAGNOSIS OF INVASIVE ASPERGILLOSIS......Page 411 B. Antigen Detection......Page 412 IV. DETECTION OF FUNGAL METABOLITES AND OTHER NONANTIGENIC COMPONENTS......Page 414 V. PCR-BASED DIAGNOSIS......Page 415 B. Histoplasmosis......Page 418 VII. SUMMARY......Page 419 REFERENCES......Page 420 I. OVERVIEW......Page 430 II. CLINICAL–ETIOLOGIC CONSTELLATIONS......Page 431 A. Chest Imaging......Page 432 IV. IMAGING IN SPECIFIC INVASIVE MYCOSES A. Aspergillosis......Page 433 B. Candidiasis......Page 438 C. Cryptococcosis......Page 441 D. Endemic Mycoses......Page 443 E. Other Rare Invasive Mycoses......Page 446 V. SUMMARY......Page 447 REFERENCES......Page 448 I. INTRODUCTION......Page 452 II. AMPHOTERICIN B DEOXYCHOLATE......Page 453 III. LIPID FORMULATIONS OF AMPHOTERICIN B......Page 456 A. Amphotericin B Lipid Complex......Page 458 B. Amphotericin B Colloidal Dispersion......Page 462 C. Liposomal Amphotericin B, L-AMB (AmBisome......Page 465 D. Lipid Emulsion Mixtures of Amphotericin B Deoxycholate......Page 469 E. Comparisons of the Lipid Formulations of Amphotericin B......Page 470 REFERENCES......Page 471 A. Chemistry......Page 480 II. MECHANISM OF ACTION A. Effects on 14a-Demethylase......Page 481 B. Pharmacokinetics......Page 482 C. Adverse Effects......Page 487 III. IN VITRO ACTIVITY A. Susceptibilty Testing......Page 490 B. In Vitro Spectrum of Activity......Page 491 C. Pharmacodynamic Properties......Page 493 IV. MECHANISMS OF RESISTANCE TO AZOLES......Page 495 A. Candida Species......Page 496 A. Fluconazole......Page 498 B. Itraconazole......Page 499 C. Voriconazole......Page 500 VIII. CONCLUSION......Page 501 REFERENCES......Page 502 I. A NEW ANTIFUNGAL TARGET......Page 508 II. MECHANISM OF ACTION......Page 509 III. CORRELATING IN VITRO AND IN VIVO ACTIVITY......Page 511 IV. CLINICAL EVALUATION: HOW ARE THESE DRUGS HANDLED?......Page 514 V. CLINICAL EFFICACY A. Candida......Page 517 B. Aspergillus and Other Moulds......Page 521 VI. COMBINATION THERAPY OF MYCOSES......Page 522 REFERENCES......Page 524 I. AGENTS FOR SYSTEMIC TREATMENT OF INVASIVE MYCOSES A. Inhibitors of Protein Synthesis......Page 532 II. CELL WALL ACTIVE AGENTS A. Nikkomycin Z......Page 537 III. CELL MEMBRANE ACTIVE AGENTS A. Pradimicins......Page 538 IV. AGENTS FOR SYSTEMIC TREATMENT OF MYCOSES OF THE SKIN AND ITS APPENDAGES A. Griseofulvin......Page 540 B. Terbinafine......Page 542 V. TOPICAL ANTIFUNGAL AGENTS......Page 543 REFERENCES......Page 544 A. Pharmacokinetic Drug Interactions......Page 552 A. Polyenes......Page 555 B. Azoles......Page 556 C. Echinocandins......Page 573 D. Miscellaneous......Page 575 E. Antifungal Combinations......Page 576 REFERENCES......Page 577 B. Settings of IFIs......Page 590 II. OVERVIEW OF ANTIFUNGAL HOST DEFENSES A. Innate Host Defense......Page 591 III. RATIONALE OF ADJUNCTIVE IMMUNOTHERAPY......Page 592 IV. PRECLINICAL BASIS OF IMMUNOTHERAPY A. In Vitro and In Vivo Laboratory Investigations......Page 593 B. Combined Activity of Antifungal Drugs, Phagocytes, and Cytokines......Page 597 C. Cytokine Administration......Page 598 V. RECOMMENDATIONS FOR THE USE OF HGFS AND CYTOKINES IN THE PREVENTION AND TREATMENT OF IFIS IN IMMUNOCOMPROMISED PATIENTS......Page 603 VI. WHITE BLOOD CELL TRANSFUSIONS (WBCTX)......Page 606 VII. OTHER MODES OF ADJUNCTIVE IMMUNOTHERAPY......Page 609 VIII. FUTURE DIRECTIONS......Page 610 REFERENCES......Page 611 I. RATIONALE......Page 624 II. TYPES OF PROPHYLAXIS......Page 625 B. Hematologic Malignancy......Page 626 D. Critical Care......Page 628 F. HIV Infection......Page 629 IV. ASPERGILLUS A. HCT and Hematologic Malignancy......Page 630 V. CRYPTOCOCCUS A. HIV Infection......Page 632 VII. COCCIDIOIDES A. HIV Infection......Page 633 IX. DURATION OF PROPHYLAXIS......Page 634 X. INFECTION CONTROL......Page 635 REFERENCES......Page 636 I. INTRODUCTION......Page 644 II. RATIONALE AND GOAL OF EMPIRICAL THERAPY......Page 645 III. HISTORICAL PERSPECTIVE OF EMPIRICAL ANTIFUNGAL THERAPY A. To Treat Empirically......Page 646 IV. THE EVOLVING EMPIRICAL ARSENAL......Page 647 V. TOWARDS PREEMPTIVE OR EARLY-THERAPY STRATEGIES......Page 651 VI. FUTURE PERSPECTIVES......Page 652 REFERENCES......Page 653 A. Amphotericin B Deoxycholate......Page 660 C. Fluconazole and Other Azoles......Page 662 D. Caspofungin......Page 663 G. Practical Considerations......Page 664 B. Lipid Formulations of Amphotericin B......Page 665 E. Itraconazole......Page 667 I. Adjunctive Measures......Page 668 IV. CRYPTOCOCCUS......Page 669 B. Meningitis or Pulmonary Infection in Immunocompromised Patients......Page 670 B. Other Immunocompromised Patients......Page 674 VII. OTHER FUNGI A. Other Yeasts......Page 676 B. Other Molds......Page 677 VIII. PNEUMOCYSTIS JIROVECI (FORMERLY......Page 678 REFERENCES......Page 679 Index......Page 690 About the Editors......Page 698 Back cover......Page 700