Carol A. Kauff man · Peter G. Pappas Editors Jack D. Sobel · William E. Dismukes Essentials of Clinical Mycology Second Edition Essentials of Clinical Mycology wwwwwwwwwwwwwwwww Carol A. Kauffman Peter G. Pappas (cid:76) Jack D. Sobel William E. Dismukes (cid:76) Editors Essentials of Clinical Mycology Second Edition Editors Carol A. Kauffman, M.D. Jack D. Sobel, M.D. Professor of Internal Medicine Professor of Internal Medicine Division of Infectious Diseases Division of Infectious Diseases University of Michigan Medical School Detroit Medical Center Veterans Affairs Ann Arbor Healthcare System Wayne State University School of Medicine Ann Arbor, MI, USA Detroit, MI, USA [email protected] [email protected] Peter G. Pappas, M.D. William E. Dismukes, M.D. Professor of Medicine Professor Emeritus of Medicine Division of Infectious Diseases Division of Infectious Diseases University of Alabama at Birmingham University of Alabama at Birmingham School of Medicine School of Medicine Birmingham, AL, USA Birmingham, AL, USA [email protected] [email protected] ISBN 978-1-4419-6639-1 e-ISBN 978-1-4419-6640-7 DOI 10.1007/978-1-4419-6640-7 Springer New York Dordrecht Heidelberg London 1st edition: © Oxford University Press, 2003 2nd edition: © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. 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The publisher makes no warranty, express or im-plied, with respect to the material contained herein Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface to the Second Edition Since the publication of the first edition of this book in 2003, the field of clinical mycology has burgeoned. This is in no small measure due to increasing numbers of immunosuppressed hosts. Transplants of both solid organs and stem cells have become commonplace. In addition to patients who classically have been considered to be immune compromised, the expanded use of immune modifiers, such as tumor necrosis factor antagonists and other monoclonal antibod- ies, has created new populations at risk for fungal infections. Advances in intensive care have allowed survival of desperately ill patients, but also have created another population group at high risk for invasive fungal infections. Our understanding of the epidemiology of fungal infections has expanded with detailed studies on risk factors and effects of various prophylac- tic regimens in specific at-risk populations and with the use of newer molecular methods. The treatment of fungal infections has improved markedly in the few short years since the first edition was published. New antifungal agents have been licensed for use, and indications for the use of various antifungal agents have changed. New agents in the echinocandin and azole classes of drugs and the increasing use of lipid formulations of amphotericin B have allowed safer and more effective therapy for severe fungal infections, especially in immuno- suppressed patients. The scientific basis of antifungal therapy has been enhanced with new studies on the pharmacodynamics and pharmacokinetics of these agents. Unfortunately, and perhaps not unexpectedly, these positive developments have been tempered by increasing resistance to several classes of antifungal agents. For each of the medically important fungal diseases, we have attempted to integrate basic aspects of mycology pertinent to an understanding of pathogenesis of infection with an exten- sive discussion of clinical manifestations, diagnosis, and treatment. Color photographs are used extensively to illustrate the many different manifestations of fungal infections. The book is organized, as before, into several distinct sections and is extensively indexed to allow easy access to the topics pertinent to patients cared for by busy clinicians. Part I gives a general overview of laboratory aspects of mycology, emphasizing newer molecular techniques that are assuming increasing importance in diagnosis, and of epidemiologic trends in fungal infections. The chapters in Part II give an in-depth review of the antifungal agents available for the treatment of systemic fungal infections. In addition, specific chapters deal with the expand- ing area of pharmacokinetics and pharmacodynamics, the increasing problem of antifungal resistance, and the use of combination antifungal therapy. Parts III–VI are devoted to individ- ual fungal diseases, and are arranged by diseases caused by yeasts (Part III), moulds (Part IV), dimorphic or endemic fungi (Part V), and other mycoses (Part VI). The final section (Part VII) is devoted to specific immunosuppressed populations who are at high risk for fungal infections. It is hoped that this text will provide a valuable resource for clinicians who do battle with the medically important fungi in their daily practices, as well as for those who only infre- quently are faced with the “odd case” that could possibly be an unusual fungal infection. C.A.K., P.G.P., J.D.S., W.E.D. v wwwwwwwwwwwwwwwww Contents Part I Introduction Laboratory Aspects of Medical Mycology............................... 3 Mary E. Brandt, Shawn R. Lockhart, and David W. Warnock Epidemiology of Systemic Fungal Diseases: An Overview.................. 27 Benjamin J. Park, Tom M. Chiller, Mary E. Brandt, and David W. Warnock Part II Systemic Antifungal Drugs Amphotericin B .................................................... 41 Stanley W. Chapman, John D. Cleary, and P. David Rogers Flucytosine ........................................................ 57 Robert A. Larsen Azoles ............................................................ 61 David R. Andes and William E. Dismukes Echinocandins ..................................................... 95 Andreas H. Groll, Dominik Schrey, and Thomas J. Walsh Terbinafine ........................................................ 113 Peter G. Pappas Antifungal Pharmacokinetics and Pharmacodynamics.................... 121 David R. Andes and Alex J. Lepak Resistance to Antifungal Drugs ....................................... 135 Dominique Sanglard Combination Antifungal Therapy ..................................... 153 Elizabeth Dodds Ashley and Melissa D. Johnson Part III Mycoses Caused by Yeasts Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Jose A. Vazquez and Jack D. Sobel Cryptococcosis ..................................................... 207 John W. Baddley and William E. Dismukes Rhodotorula, Saccharomyces, Malassezia, Trichosporon, Blastoschizomyces, and Sporobolomyces................................ 227 Jose A. Vazquez Part IV Mycoses Caused by Moulds Aspergillosis ....................................................... 243 Thomas F. Patterson vii viii Contents Mucormycosis and Entomophthoramycosis (Zygomycosis) ................ 265 Ashraf S. Ibrahim, John E. Edwards, Jr, Scott G. Filler, and Brad Spellberg Hyalohyphomycoses (Hyaline Moulds) ................................. 281 Harrys A. Torres and Dimitrios P. Kontoyiannis Phaeohyphomycoses (Brown-Black Moulds) ............................ 305 John R. Perfect, Barbara D. Alexander, and Wiley A. Schell Part V Mycoses Caused by Dimorphic Fungi Histoplasmosis ..................................................... 321 Carol A. Kauffman Blastomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 Robert W. Bradsher and J. Ryan Bariola Coccidioidomycosis ................................................. 349 Neil M. Ampel Paracoccidioidomycosis.............................................. 367 Angela Restrepo, Angel Gonzalez, and Carlos A. Agudelo Sporotrichosis...................................................... 387 Peter G. Pappas Penicilliosis ........................................................ 399 Kenrad E. Nelson, Khuanchai Supparatpinyo, and Nongnuch Vanittanakom Part VI Mycoses Involving Skin and Subcutaneous Tissues Eumycetoma....................................................... 415 Beatriz Bustamante and Pablo E. Campos Chromoblastomycosis ............................................... 427 John W. Baddley and William E. Dismukes Part VII Other Mycoses Pneumocystosis..................................................... 437 Catherine F. Decker and Henry Masur Infections due to Miscellaneous Fungi.................................. 455 John W. Baddley and William E. Dismukes Part VIII Special Patient Populations Fungal Infections in Neutropenic Patients............................... 465 Juan C. Gea-Banacloche, Andreas H. Groll, and Thomas J. Walsh Fungal Infections in Stem Cell Transplant Recipients..................... 497 Dionissios Neofytos and Kieren A. Marr Fungal Infections in Solid Organ Transplant Recipients................... 511 Peter G. Pappas Fungal Infections Among Patients with AIDS ........................... 525 Olivier Lortholary and Bertrand Dupont Index. . . . . . . . . . ....................................................... 537 Contributors Carlos A. Agudelo M.D. Department of Internal Medicine, Corporacion para Investigaciones Biologicas, School of Medical Sciences, Universidad Pontificia Bolivriana, Medellin, Colombia [email protected] Barbara D. Alexander M.D. Duke Mycology Research Unit, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, NC, USA [email protected] Neil M. Ampel M.D. Division of Infectious Diseases, Southern Arizona Veterans Affairs Health Care Center, University of Arizona, Tucson, AZ, USA [email protected] David R. Andes M.D. Department of Medicine, and Medical Microbiology and Immunology, Section of Infectious Diseases, Madison, WI, USA [email protected] John W. Baddley M.D., MSPH Division of Infectious Diseases, Birmingham VA Medical Center, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA [email protected] J. Ryan Bariola M.D. University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, AR, USA [email protected] Robert W. Bradsher Jr M.D. University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, AR, USA [email protected] Mary E. Brandt Ph.D. Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA [email protected] ix