Flucytosine and cryptococcosis: which in vitro test is the best predictor of outcome?
ABSTRACT The combination of flucytosine and amphotericin B is first choice treatment for active cryptococcosis. Because of innate or acquired resistance of Cryptococcus neoformans to flucytosine, in vitro testing is mandatory. Yeast nitrogen base (YNB) at pH 7.0 is the recommended medium for the broth microdilution test (NCCLS M27-A) and for the E-test. In order to verify if minimum inhibitory concentrations (MICs) were able to predict treatment outcome, the susceptibility of 24 isolates from 21 patients treated with flucytosine alone or in combination was tested by the broth microdilution, agar dilution and E-test using YNB either at pH 7.0 or at pH 5.4. Only those MICs obtained on YNB pH 5.4 proved to correlate with treatment outcome. The present study suggests that in vitro susceptibility to flucytosine of C. neoformans isolates should be evaluated on YNB pH 5.4 and the test should be standardized accordingly.
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ABSTRACT: The antifungal agent flucytosine was found to be active in vitro against Aspergillus fumigatus isolates when the MIC was determined at pH 5.0 instead of pH 7.0. The in vitro MIC at pH 5.0 corresponded to the in vivo efficacy of flucytosine monotherapy in a murine model of invasive aspergillosis.Antimicrobial Agents and Chemotherapy 10/2008; 52(12):4483-5. · 4.57 Impact Factor
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ABSTRACT: Cryptococcus diffluens is a recently re-established species that shares several phenotypic features with Cryptococcus neoformans. We evaluated the application of the Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) macro- and microbroth dilution methods and the E-test agar diffusion method to determine the in vitro susceptibilities of known strains of C. diffluens against amphotericin B (AMB), flucytosine (5-FC), fluconazole (FLC), itraconazole (ITC) and the novel triazoles, voriconazole (VRC) and posaconazole (PSC). Seven strains were found to be resistant in vitro to AMB (MICs >/=2 microg/ml), five were resistant to 5-FC (MICs of >/=32 microg/ml), four were resistant to FLC (MICs of FLC >/=32 microg/ml) and nine were resistant to ITC (MICs of ITC >1 microg/ml). In contrast, VRC and PSC showed good in vitro activity against C.diffluens strains, even those with elevated MICs to amphotericin B and/or established azoles. Most of the isolates were inhibited by 0.5 microg/ml of both VRC and PSC. A clinical isolate showing phenotypic switching exhibited elevated MICs to both agents, i.e., VRC (>16 microg/ml) and PSC (>8 microg/ml).Medical Mycology 03/2009; 47(2):169-76. · 1.98 Impact Factor
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ABSTRACT: Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with AIDS (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5μg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC≤4μg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102μg/mL and 0.396μg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC≤8μg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC≤0.25μg/mL). The geometric mean MIC of fluconazole stood at 15.14μg/mL and of itraconazole was 0.144μg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions.Journal de Mycologie MÃ©dicale/Journal of Medical Mycology 09/2012; 22(3):243-8. · 0.74 Impact Factor