Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998

The antifungal drug susceptibilities of two collections of Cryptococcus neo formans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determine d. The MICs of fluconazole, itraconazole, and flucytosine were determined b y the National Committee for Clinical Laboratory Standards broth microdilut ion 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 (MIC(50)s), and the MIC(90)s of these four antifungal agents did not chang e from 1992 to 1998. In addition, very small numbers of isolates showed ele vated MICs suggestive of in vitro resistance. The MICs of amphotericin B we re elevated (greater than or equal to2 mug/ml) for 2 isolates, and the MICs of flucytosine were elevated (greater than or equal to 32 mug/ml) for 14 i solates. Among the azoles, the fluconazole MIC was elevated (greater than o r equal to 64 mug/ml) for 8 isolates and the itraconazole MIC (greater than or equal to1 mug/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 isol ates 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 de crease in the fluconazole MIC over a 1-month period. We conclude that in vi tro resistance to antifungal agents remains uncommon in C. neoformans and h as not significantly changed with time during the past decade.