Trends in antifungal drug susceptibility of Cryptococcus species in South Africa, 2002-2008

Govender N.

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Cryptococcosis, most commonly caused by the fungal pathogen Cryptococcus neoformans, is a common, laboratory- confirmed, AIDS-defining, opportunistic infection in South Africa. Fluconazole, which has been widely available at no cost through a philanthropic programme since 2000, is frequently used for treatment of HIV -infected patients with newly diagnosed cryptococcal disease, as well as severe or refractory candidiasis. In order to monitor antifungal drug susceptibility trends, testing was performed on cryptococcal isolates obtained from patients through ongoing, active, population-based, laboratory-based surveillance. Susceptibility to fluconazole for randomly selected, incident- episode isolates from patients at four Gauteng Province hospitals was compared for two periods (2002-2003 and 2007-2008) with no change, demonstrated to date, in fluconazole minimum inhibitory concentration (MIC) range, MIC50 and MIC90, as determined by the Etest® (AB bioMí©rieux, Solna, Sweden). These Etest® MIC results will be confirmed by a reference broth microdilution method. In addition, susceptibility testing will be expanded to include a wider panel of antifungal drugs (amphotericin B, flucytosine, voriconazole and posaconazole). Analysis of fluconazole MICs determined by reference methodology, from isolates obtained serially from 92 patients with consecutive cryptococcal episodes, showed that a fourfold-increase in MIC occurred between the incident-episode and recurrent- episode isolate in a very small proportion of cases (5192, 5%). In the absence of interpretive breakpoints, a four-fold increase in fluconazole MIC may indicate in-vitro resistance. Despite reports to the contrary, preliminary data suggest that in-vitro fluconazole resistance amongst South African, clinical isolates has not changed substantially over 6 years, and remains relatively uncommon even amongst isolates from patients with recurrent disease.

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17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)