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Antimicrobial Agents and Chemotherapy, November 2001, p. 3065-3069, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3065-3069.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates in the United States: 1992 to 1994 and 1996 to 1998

Mary E. Brandt,1,* Michael A. Pfaller,2 Rana A. Hajjeh,1 Richard J. Hamill,3 Peter G. Pappas,4 Arthur L. Reingold,5 David Rimland,6 and David W. Warnock1,dagger for the Cryptococcal Disease Active Surveillance Group

Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention,1 and Veterans Administration Medical Center and Emory University School of Medicine,6 Atlanta, Georgia; Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa2; Veterans Administration Medical Center and Baylor College of Medicine, Houston, Texas3; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama4; and School of Public Health, University of California at Berkeley, Berkeley, California5

Received 7 May 2001/Returned for modification 14 July 2001/Accepted 3 August 2001

The antifungal drug susceptibilities of two collections of Cryptococcus neoformans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determined. The MICs of fluconazole, itraconazole, and flucytosine were determined by the National Committee for Clinical Laboratory Standards broth microdilution method; amphotericin B MICs were determined by the E-test. Our results showed that the MIC ranges, the MICs at which 50% of isolates are inhibited (MIC50s), and the MIC90s of these four antifungal agents did not change from 1992 to 1998. In addition, very small numbers of isolates showed elevated MICs suggestive of in vitro resistance. The MICs of amphotericin B were elevated (>= 2 µg/ml) for 2 isolates, and the MICs of flucytosine were elevated (>= 32 µg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (>= 64 µg/ml) for 8 isolates and the itraconazole MIC (>= 1 µg/ml) was elevated for 45 isolates. Analysis of 172 serial isolates from 71 patients showed little change in the fluconazole MIC over time. For isolates from 58 patients (82% of serial cases) there was either no change or a twofold change in the fluconazole MIC. In contrast, for isolates from seven patients (12% of serial cases) the increase in the MIC was at least fourfold. For isolates from another patient there was a 32-fold decrease in the fluconazole MIC over a 1-month period. We conclude that in vitro resistance to antifungal agents remains uncommon in C. neoformans and has not significantly changed with time during the past decade.

* Corresponding author. Mailing address: Mycotic Diseases Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., Mailstop G-11, Atlanta, GA 30333. Phone: (404) 639-0281. Fax: (404) 639-3546. E-mail: Mbrandt{at}cdc.gov.

dagger Study group members are listed in the appendix.

Antimicrobial Agents and Chemotherapy, November 2001, p. 3065-3069, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3065-3069.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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