Chapter 16
Drug Resistance in Cryptococcus: Epidemiology and Molecular Mechanisms
M. A. Pfaller,
J. K. Lodge,
M. A. Ghannoum,
M. A. Pfaller
Departments of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, IA, 52242-1009
Search for more papers by this authorJ. K. Lodge
Department of Molecular Microbiology, Washington University of School of Medicine, St. Louis, MO, 63110
Search for more papers by this authorM. A. Ghannoum
Center for Medical Mycology, Case Western Reserve University, Cleveland, OH, 44106
Search for more papers by this authorM. A. Pfaller,
J. K. Lodge,
M. A. Ghannoum,
M. A. Pfaller
Departments of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, IA, 52242-1009
Search for more papers by this authorJ. K. Lodge
Department of Molecular Microbiology, Washington University of School of Medicine, St. Louis, MO, 63110
Search for more papers by this authorM. A. Ghannoum
Center for Medical Mycology, Case Western Reserve University, Cleveland, OH, 44106
Search for more papers by this authorBook Editor(s):Joseph Heitman,
Thomas R. Kozel,
Kyung J. Kwon-Chung,
John R. Perfect,
Arturo Casadevall,
Joseph Heitman
Duke University Medical Center, Durham, NC, 27710
Search for more papers by this authorThomas R. Kozel
University of Nevada School of Medicine, Reno, NV, 89557-0320
Search for more papers by this authorKyung J. Kwon-Chung
National Institute of Allergy and Infectious Diseases, Bethesda, MD, 20892
Search for more papers by this authorJohn R. Perfect
Duke University Medical Center, Durham, NC, 27710
Search for more papers by this authorArturo Casadevall
Albert Einstein College of Medicine, Bronx, NY, 10461
Search for more papers by this authorFirst published: 12 November 2010
Summary
This chapter describes the epidemiology of antifungal drug resistance as identified by in vitro susceptibility testing and studies of the mechanisms of resistance in Cryptococcus neoformans and C. gattii. Taking into consideration the MIC distribution profiles for the various antifungal agents, the pharmacology of the antifungal drugs, and studies of resistance mechanisms and clinical outcomes, it is reasonable to adapt the breakpoints developed by the Clinical and Laboratory Standards Institute (CLSI) for Candida spp. for use in the discussion of antifungal resistance in C. neoformans and C. gattii. Resistance to flucytosine may develop from decreased uptake (loss of permease activity) or loss of enzymatic activity required for the conversion of flucytosine to 5-fluorouracil (cytosine deaminase) and 5-fluorouridylic acid (FUMP pyrophosphorylase). The echinocandin class of antifungals is relatively ineffective against Cryptococcus sp., but the mechanism of this resistance is still unknown. The epidemiology of antifungal resistance in the pathogenic cryptococci is a dynamic process that differs considerably according to the status of health care, especially that devoted to HIV and AIDS, in the region of interest. Improved understanding of the mechanisms of antifungal resistance in cryptococci will ultimately help in the battle against emerging resistance.
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