Fundamental Medical Mycology Errol Reiss

Fundamental Medical Mycology Fundamental Medical Mycology Errol Reiss Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia H. Jean Shadomy Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia G. Marshall Lyon, III Department of Medicine, Division of Infectious Diseases, Emory University, School of Medicine, Atlanta, Georgia A JOHN WILEY & SONS, INC., PUBLICATION This book was written by Errol Reiss in his private capacity. No official support or endorsement by the Centers for Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred. Copyright 2012 by Wiley-Blackwell. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission. 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For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data: Reiss, Errol. Fundamental medical mycology / Errol Reiss, H. Jean Shadomy, and G. Marshall Lyon III. p. ; cm. Includes bibliographical references and index. ISBN 978-0-470-17791-4 (cloth) 1. Medical mycology. I. Shadomy, H. Jean. II. Lyon, G. Marshall. III. Title. [DNLM: 1. Mycology–methods. 2. Mycoses–microbiology. 3. Mycoses–therapy. QY 110] QR245.R45 2012 616.96901–dc22 2011009910 Printed in the United States of America oBook ISBN: 978-1-118-10177-3 ePDF ISBN: 978-1-118-10175-9 ePub ISBN: 978-1-118-10176-6 10987654321 To our spouses, with gratitude: Cheryl (E. R.), “Shad” (H. J. S.), and Tabitha (G. M. L.) Contents Preface xvii 1.6.2 Investigating Outbreaks 10 1.6.3 Determining the Susceptibility to Acknowledgments xix Antifungal Agents 10 1.6.4 Estimating the Significance of Fungi Generally Considered to be Opportunists or Saprobes 10 1.6.5 Types of Vegetative Growth 10 Part One Introduction to Fundamental Medical 1.7 Sporulation 11 Mycology, Laboratory Diagnostic Methods, 1.8 Dimorphism 11 and Antifungal Therapy 1.8.1 Dimorphism and Pathogenesis 12 1.9 Sex in Fungi 13 1. Introduction to Fundamental Medical 1.9.1 Anamorph and Teleomorph Mycology 3 Nomenclature 13 1.10 Classification of Mycoses Based on the 1.1 Topics not Covered, or Receiving Secondary Primary Site of Pathology 13 Emphasis 3 1.10.1 Superficial Mycoses 13 1.2 Biosafety Considerations: Before You Begin 1.10.2 Cutaneous Mycoses 13 Work with Pathogenic Fungi... 3 1.10.3 Systemic Opportunistic Mycoses 13 1.2.1 Biological Safety Cabinets (BSC) 4 1.10.4 Subcutaneous Mycoses 13 1.2.2 Precautions to Take in Handling Etiologic 1.10.5 Endemic Mycoses Caused by Dimorphic Agents that Cause Systemic Mycoses 4 Environmental Molds 13 1.2.3 Additional Precautions at Biosafety 1.11 Taxonomy/Classification: Kingdom Level 3 (BSL 3) 5 Fungi 14 1.2.4 Safety Training 5 1.11.1 The Phylogenetic Species Concept for 1.2.5 Disinfectants and Waste Disposal 5 Classification 15 1.3 Fungi Defined: Their Ecologic Niche 5 1.11.2 The Higher Level Classification of 1.4 Medical Mycology 5 Kingdom Fungi 15 1.5 A Brief History of Medical Mycology 6 1.12 General Composition of the Fungal 1.5.1 Ancient Greece 6 Cell 21 1.5.2 Middle Ages 6 1.12.1 Yeast Cell Cycle 21 1.5.3 Twentieth Century 6 1.12.2 Hyphal Morphogenesis 21 1.5.4 Endemic Mycoses in the Americas 6 1.12.3 Cell Wall 22 1.5.5 Era of Immunosuppression in the 25 Treatment of Cancer, Maintenance of 1.13 Primary Pathogens 1.13.1 Susceptibility to Primary Organ Transplants, and Autoimmune Pathogens 26 Diseases 7 1.5.6 Opportunistic Mycoses 7 1.14 Endemic Versus Worldwide Presence 26 1.5.7 HIV/AIDS 7 1.15 Opportunistic Fungal Pathogens 26 1.5.8 Twenty-first Century 8 1.15.1 Susceptibility to Opportunistic Fungal 1.6 Rationale for Fungal Identification 9 Pathogens: Host Factors 26 1.6.1 Developing the Treatment Plan 9 1.16 Determinants of Pathogenicity 27 vii viii Contents General References in Medical Selected References for Laboratory Mycology 27 Diagnostic Methods in Medical Selected References for Introduction to Mycology 69 Fundamental Medical Mycology 28 Websites Cited 70 Websites Cited 29 Commercial Manufacturers and Suppliers of Questions 30 Fungal Media, Stains, and Reagents 71 Packing and Shipping of Infectious Agents 2. Laboratory Diagnostic Methods in Medical and Clinical Specimens 72 Mycology 31 Questions 72 2.1 Who Is Responsible for Identifying 3A. Antifungal Agents and Therapy 75 Pathogenic Fungi? 31 2.1.1 Role of the Clinical Laboratorian 31 3A.1 Introduction 75 2.1.2 Role of the Physician 31 3A.1.1 Major Antifungal Agents Approved for 2.2 What Methods are Used to Identify Clinical Use 76 Pathogenic Fungi? 31 3A.1.2 Comparison of Antibacterial and 2.2.1 Culture and Identification 31 Antifungal Agents According to Their 2.3 Laboratory Detection, Recovery, and Intracellular Targets 79 3A.2 Amphotericin B (AmB-deoxycholate) Identification of Fungi in the Clinical Microbiology Laboratory 33 (Fungizone , Apothecon Subsidiary of 2.3.1 The Laboratory Manual 33 Bristol-Myers-Squibb) 80 2.3.2 Specimen Collection 33 3A.2.1 Structure 80 2.3.3 Direct Examination 34 3A.2.2 Mode of Action 80 2.3.4 Histopathology 36 3A.2.3 Indications 82 2.3.5 Culture 37 3A.2.4 Formulation 82 2.3.6 Storage and Cryopreservation of Cultures 3A.2.5 Spectrum of Activity 82 for QA and QC in the Clinical Mycology 3A.2.6 Clinical Uses 82 Laboratory 41 3A.2.7 Lipid Formulations of AmB 83 2.3.7 Media and Tests for Yeast 3A.2.8 Pharmacokinetics 84 Identification 42 3A.2.9 Interactions 85 3A.2.10 Adverse Reactions 85 2.3.8 Methods Useful for Mold Identification 45 3A.3 Fluconazole (FLC) (Diflucan , 2.3.9 Microscopy Basics 53 Pfizer) 86 2.3.10 Use of Reference Laboratories 59 3A.3.1 Structure and Mode of Action 86 2.3.11 Fungal Serology and Biochemical 3A.3.2 Indications 86 Markers of Infection 59 3A.3.3 Fluconazole Pharmacokinetics 87 2.4 Genetic Identification of Fungi 64 3A.3.4 Efficacy 88 2.4.1 Commercial Test 64 3A.3.5 Formulations 88 2.4.2 Peptide Nucleic Acid–Fluorescent In Situ 3A.3.6 Interactions 88 3A.3.7 Adverse Reactions 88 Hybridization (PNA-FISH) 64 2.4.3 PCR-Sequencing Method 64 3A.4 Itraconazole (ITC) (Sporanox , Janssen 2.4.4 Nuclear rDNA Complex 64 Pharmaceutica Division of Johnson & 2.4.5 Genetic Tools for Species Johnson) 89 Identification 66 3A.4.1 Action Spectrum 89 2.4.6 How Is the Genetic Identification of an 3A.4.2 ITC: Uncertain Bioavailability 89 Unknown Fungus Accomplished? 66 3A.4.3 Properties 89 2.4.7 Growth of the Fungus in Pure Culture, 3A.4.4 Pharmacokinetics 89 Extraction and Purification of DNA 66 3A.4.5 Interactions 90 2.4.8 PCR of the Target Sequence 67 3A.4.6 Adverse Reactions 90 2.4.9 PCR Cycle Sequencing 68 3A.5 Voriconazole (VRC) (Vfend, 2.4.10 Assemble the DNA Sequence 68 Pfizer) 90 2.4.11 Perform a BLAST Search 68 3A.5.1 Action Spectrum 90 2.4.12 The MicroSeq System 68 3A.5.2 Pharmacokinetics 90 2.4.13 Other Sequence Databases 68 3A.5.3 Drug Interactions 91 General References for Laboratory 3A.5.4 Adverse Reactions 91 Diagnostic Methods in Medical 3A.6 Posaconazole (PSC) (Noxafil, Mycology 69 Schering-Plough/Merck & Co.) 91 Contents ix 3A.6.1 Action Spectrum 91 3A.14.1 Mode of Action 99 3A.6.2 Pharmacokinetics 91 3A.14.2 Action Spectrum 99 3A.6.3 Drug Interactions 92 3A.14.3 Indications 99 3A.6.4 Adverse Reactions 92 3A.14.4 Dosage Regimen 99 3A.7 Azole Resistance Mechanisms 92 3A.14.5 Metabolism 99 3A.7.1 Alteration of Target Enzyme 3A.14.6 Adverse Reactions 100 (Lanosterol Demethylase) 92 3A.15 Combination Therapy 100 3A.7.2 Overexpression of Target 3A.16 Suppressive or Maintenance Enzyme 92 Therapy 100 3A.7.3 Increased Efflux of Drug, CDR Efflux 3A.17 Prophylactic Therapy 100

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