Comparison of Two Methods and Three End Points in Determination of In Vitro Activity of Micafungin against Aspergillus spp

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Abstract
We investigated the in vitro activity of micafungin against clinical Aspergillus isolates ( n = 37) ( Aspergillusfumigatus [ n = 21], Aspergillusflavus [ n = 14], and Aspergillus niger [ n = 2]) by using NCCLS M38A microdilution and an investigational disk diffusion assay. Microdilution assay results were evaluated by using the end points of a MIC-2 (measured in micrograms per milliliter) and minimum effective concentration (MEC, measured in micrograms per milliliter; the lowest concentration of micafungin that produces short and aberrant hyphal branchings microscopically). Disk diffusion results were interpreted by measuring the zone(s) of inhibition (ZOI, measured in millimeters). Micafungin proved to be similarly active against all Aspergillus species tested. At 24 h, MIC-2s and MECs were identical. At 48 h, however, MIC-2s increased unpredictably, leading to the loss of a consistent correlation between the two end points. MECs and ZOI remained consistent and correlated at both reading times, suggesting their use as relevant end points in susceptibility testing of micafungin against Aspergillus . All Aspergillus isolates yielded intrazonal growth on disk diffusion agar plates. The intrazonal colonies contained short, aberrant hyphal branchings microscopically. The in vivo significance of these findings remains to be further investigated.