In vitro fungicidal activity of voriconazole against six Aspergillus species



Objective. The most important role of susceptibility testing is to identify potential resistance to the antimicrobial agent being evaluated. The NCCLS has proposed optimal conditions for testing the fungistatic MICs antifungal susceptibilities of conidium-forming filamentous fungi with the established agents (NCCLS M38-P document). This study evaluated the in vitro fungistatic MICs and fungicidal MFCs activities of voriconazole against 18 Aspergillus flavus, 57 A. fumigatus, 9 A. nidulans, 7 A. niger, 1 A. sydowii and 14 A. terreus.Methods. MICs were determined following the NCCLS M38-P broth microdilution method: RPMI-1640 broth, non-germinated conidia inoculum (104 CFU/ml) and incubation at 35'C for 48 h. Both complete MICS-0: 100%) and prominent MIC-2: 50%) growth inhibition were determined. MFCs corresponded to the lowest drug dilution that showed no growth or 8 mg/ml and the MFC50s and MFC90s from 1 to 2 mg/mi for 5 of 6 the species tested. The exceptions were the MFC50 (4 mg/ml) and MFC90 (>8 mg/ml) values for A. terreus. The overall voriconazole MIC-0 range (0.06-4 mg/ml) was higher than the MIC-2 (0.01-1 mg/ml), but corresponding MIC50s and MIC90s were similar (0.2 and 0.5 vs 0.5 and 1 mg/ml, respectively).Conclusions. These preliminary data suggest that voriconazole had in vitro fungicidal activity against most isolates of aspergillus tested. The role of either fungicidal or fungistatic data as predictors of antifungal resistance is to be established in clinical trials.

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5th Trends in Invasive and Fungal Infections
    • TIFI 5th