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Therapeutic Guidelines in Systemic Fungal Infections Therapeutic Guidelines in Systemic Fungal Third Edition Infections

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Therapeutic Guidelines in Systemic Fungal Infections Therapeutic Guidelines in Systemic Fungal Third Edition Infections FUNGAL_cover 9-12-2003 15:17 Pagina 1 Therapeutic Guidelines in Systemic Fungal Infections Therapeutic Guidelines in Systemic Fungal Third Edition Infections Third Edition Malcolm D Richardson Malcolm D Richardson Brian L Jones • Brian L Jones Current CML Medical AB5092 Literature FUNGAL_3d 10-12-2003 16:56 Pagina i Therapeutic Guidelines in Systemic Fungal Infections Third Edition Malcolm D Richardson PhD, FIBiol, FRCPath Senior Lecturer in Medical Mycology Department of Bacteriology & Immunology University of Helsinki and Consultant in Clinical Mycology Helsinki University Central Hospital Laboratory Diagnostics Helsinki, Finland Brian L Jones BSc MBChB, FRCPath Consultant Medical Microbiologist & Honorary Senior Clinical Lecturer Department of Medical Microbiology Glasgow Royal Infirmary, Glasgow, UK Current Medical Literature FUNGAL_3d 10-12-2003 16:56 Pagina iii Contents Preface to the First Edition vii Preface to the Third Edition viii Clinical and Laboratory Diagnosis 1 1 Definitions of fungal infections 2 Categories of risk groups for systemic fungal 2 infection 7 Essential clinical examination in neutropenic 3 and solid organ transplant patients with suspected invasive fungal infection 8 Investigation of pulmonary infection in 4 neutropenic and solid organ transplant patients 9 Essential investigations for the laboratory 5 diagnosis of systemic fungal infections 10 Fungal species most commonly recovered 6 from clinical specimens 17 Criteria for the diagnosis of systemic fungal 7 infections: clinical features and laboratory parameters contributing to a definitive diagnosis 19 Assessment of the response to antifungal 8 therapy – definitions 22 iii FUNGAL_3d 10-12-2003 16:56 Pagina iv Antifungal Drugs 23 9 Amphotericin B 24 Regimen for rapid escalation of amphotericin B 10 dosage 27 Regimen for gradual escalation of 11 amphotericin B dosage 28 12 Liposomal amphotericin B (AmBisome®) 29 Amphotericin B colloidal dispersion 13 (Amphocil®, Amphotec®) 33 14 Amphotericin B lipid complex (Abelcet®) 37 Pharmacokinetic comparisons of 15 amphotericin B formulations 40 Polyene comparisons: infusion-related 16 reactions 41 17 Polyene comparisons: nephrotoxicity 43 18 Caspofungin 44 19 Fluconazole 48 20 Flucytosine (5-fluorocytosine) 53 Regimens for administration of flucytosine in 21 renal impairment 56 iv FUNGAL_3d 10-12-2003 16:56 Pagina v 22 Itraconazole 57 23 Voriconazole 64 Therapy of Specific Infections 69 24 Aspergillosis 70 25 Prevention of invasive aspergillosis 75 26 Blastomycosis 78 27 Candidosis 80 28 Coccidioidomycosis 86 29 Cryptococcosis 88 30 Histoplasmosis 91 31 Mucormycosis 94 32 Paracoccidioidomycosis 96 33 Penicillium marneffei infection 97 34 Sporotrichosis 98 v FUNGAL_3d 10-12-2003 16:56 Pagina vi 35 Unusual fungal infections 99 Prophylaxis 101 36 Prophylaxis alternatives 102 Examples of risk factors triggering targeted 37 prophylaxis/pre-emptive therapy 105 Empirical Treatment of the Persistently Febrile Neutropenic Patient 106 38 Recommended empirical treatment 107 39 Current recommended initial strategy 108 Combination Treatment and Antifungals Under Development 109 40 Combination therapy: the issues 110 41 Antifungals under development 111 General references 115 Web sites 117 Abbreviations 118 vi FUNGAL_3d 10-12-2003 16:56 Pagina vii Preface to the First Edition This guide is intended as a unique resource for clinicians responsible for the management of patients with systemic fungal infections. Up-to-date information is combined with the authors’ extensive experience in the field and is presented in a clear, well-designed format. The text focuses on three main areas and is displayed in the form of tables for easy accessi- bility: • Clinical and Laboratory Diagnosis presents the essential examinations, investigations, and criteria for the diagnosis of systemic fungal infections • Antifungal Drugs introduces currently available antifungal agents and provides details on their uses, typical dosages, adverse effects, and pharmaceutics/pharmacokinetics • Therapy of Specific Infections describes preventative strategies and therapies against individual organisms and diseases. Separate sections cover Prophylaxis and Empirical Treatment of the Persistently Febrile Neutropenic Patient, and a General References list is provided. Dosage recommendations are based on the prescribing information for each antifungal agent and are accurate at the time of publication. The authors have made a special effort to ensure that the dosage recommendations are accurate and in agreement with the standards and col- lective opinion accepted at the time of publication. The formulations and usage described do not necessarily have specific approval by the regulatory authorities of all countries. Since dosage regimens and contraindications may be regularly reviewed and revised, further editions of this guide are envisaged in order to keep this information updated. vii FUNGAL_3d 10-12-2003 16:56 Pagina viii Preface to the Third Edition An even greater understanding of the benefits and limitations of old and new antifungal agents is reflected in this edition of Therapeutic Guidelines in Systemic Fungal Infections. Each table has been revised to present antifungal treatment as it is used today, taking into account evi- dence-based recommendations that have been made since the publication of the first and sec- ond editions. New diagnostic tests such as PCR and ELISA have been assessed in immunocompromised patients. These may assist in the choice of antifungal and may be used to monitor treatment success or failure. The number of oral and parenteral antifungal agents has increased significantly and new formulations of established agents have been licensed in many countries. Furthermore, antifungal susceptibility testing has been refined. Significant progress has been made in determining the applications of these tests in routine clinical prac- tice. The use of these tests is indicated where appropriate. As previously, we have included the most relevant key publications and reviews at the ends of the tables. These provide a link to a far larger body of established literature. We have made every effort to ensure that the dosage recommendations are accurate and in agreement with the standards and collective opinion accepted at the time of publication. The formulations and usage described do not necessarily have specific approval by the regu- latory authorities of all countries. Since dosage regimens may be modified as new clinical research accumulates, readers are strongly advised to check the prescribing information to see whether changes have been made to the recommended dosages and/or contraindications for use. New antifungal agents are constantly being developed and evaluated. Some are close to being introduced into clinical practice. Significant changes in the guidelines and key publi- cations will be available on Clinical Mycology Online (www.clinical-mycology.com). Malcolm Richardson Brian Jones viii FUNGAL_3d 10-12-2003 16:56 Pagina 1 Clinical and Laboratory Diagnosis 1 Definitions of fungal infections 2 Categories of risk groups for systemic fungal infection 3 Essential clinical examination in neutropenic and solid organ transplant patients with suspected invasive fungal infection 4 Investigation of pulmonary infection in neutropenic and solid organ transplant patients 5 Essential investigations for the laboratory diagnosis of systemic fungal infections 6 Fungal species most commonly recovered from clinical specimens 7 Criteria for the diagnosis of systemic fungal infections: clinical features and laboratory parameters contributing to a definitive diagnosis 8 Assessment of the response to antifungal therapy – definitions Clinical and laboratory diagnosis ____________________________________________________________________________________________________________ 1 FUNGAL_3d 10-12-2003 16:56 Pagina 2 Definitions of fungal infections 1(i) PROVEN INVASIVE FUNGAL INFECTIONS Deep tissue infections Molds* Yeasts* Histo/cytochemistry showing hyphae or Histo/cytochemistry showing yeast cells spherules (filamentous fungi without and/or pseudohyphae from a needle aspi- yeast forms) from a needle aspiration or ration or biopsy excluding mucous mem- biopsy with evidence of associated tis- branes sue damage (either microscopically or OR unequivocally by imaging) Positive culture obtained from a normal- OR ly sterile and clinically or radiologically Positive culture obtained by a sterile pro- abnormal site consistent with infection, cedure from a normally sterile and clin- excluding urine, sinuses, and mucous ically or radiologically abnormal site membranes by a sterile procedure consistent with infection OR Microscopy (India ink, mucicarmine stain) or antigen positivity for Crypto- coccus in CSF Fungemia Molds* Yeasts* Positive blood culture of fungi exclud- Positive blood culture of Candida and ing Aspergillus species and Penicillium other yeasts in patients with temporally species, other than P. marneffei, accom- related clinical signs and symptoms panied by temporally related clinical compatible with the relevant organism signs and symptoms compatible with the relevant organism * Append identification at genus or species level if available 2 ____________________________________________________________________________________________________________ Clinical and laboratory diagnosis FUNGAL_3d 10-12-2003 16:56 Pagina 3 Definitions of fungal infections 1(ii) Endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and paracoccidioidomycosis) Either systemic
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