In Vitro Antifungal Susceptibilities and Amplified Fragment Length Polymorphism Genotyping of a Worldwide Collection of 350 Clinical, Veterinary, and Environmental Cryptococcus gattii Isolates

Abstract

The in vitro susceptibilities of a worldwide collection of 350 Cryptococcus gattii isolates to seven antifungal drugs, including the new triazole isavuconazole, were tested. With amplified fragment length polymorphism (AFLP) fingerprinting, human, veterinary, and environmental C. gattii isolates were subdivided into seven AFLP genotypes, including the interspecies hybrids AFLP8 and AFLP9. The majority of clinical isolates (n ‫؍‬ 215) comprised genotypes AFLP4 (n ‫؍‬ 76) and AFLP6 (n ‫؍‬ 103). The clinical AFLP6 isolates had significantly higher geometric mean MICs for flucytosine and fluconazole than the clinical AFLP4 isolates. Of the seven antifungal compounds examined in this study, isavuconazole had the lowest MIC 90 (0.125 g/ml) for all C. gattii isolates, followed by a 1 log 2 dilution step increase (MIC 90 , 0.25 g/ml) for itraconazole, voriconazole, and posaconazole. Amphotericin B had an acceptable MIC 90 of 0.5 g/ml, but fluconazole and flucytosine had relatively high MIC 90 s of 8 g/ml.

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

“…The majority of studies addressing in vitro susceptibility testing for amphotericin B against C. neoformans and C. gattii have shown that many of these isolates are susceptible at MIC values ≤ 1 mg/L [47,48,[50][51][52][53], similar to the MIC values obtained in this work. However, the literature reports MIC values for amphotericin B ≥ 1 µg/mL, such as Lozano-Chui et al [31], who reported MIC values of 3-4 mg/L, which were associated with treatment failure.…”

“…Following their analysis of susceptibility profiles of C. gattii genotypes, Chong et al [49] reported higher MIC values for fluconazole (≥ 64 µg/mL) against C. gattii VGII than against C. gattii VGIII and VGI [48]. Iqbal et al [50] reported differences in the susceptibility profiles of the molecular types of C. gattii, having determined higher MIC values for the VGII subtypes than the VGI and VGIII subtypes.…”

“…Hagen et al [48] analyzed 350 isolates of C. gattii originating from clinical, environmental and animal sources and reported that MIC values for flucytosine and fluconazole were higher, i.e. these antifungal drugs showed less activity in vitro against C. gattii compared with isavuconazole, itraconazole, posaconazole, and voriconazole.…”

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

“…The results of a number of studies have suggested that differences in in vitro drug susceptibility are correlated with different Cryptococcus species and molecular types (19)(20)(21)(22)(23). MICs of all azoles, particularly fluconazole, appear to be higher for molecular type VGII isolates than for other C. gattii molecular types, primarily VGI, and C. neoformans (19,21,23).…”

“…MICs of all azoles, particularly fluconazole, appear to be higher for molecular type VGII isolates than for other C. gattii molecular types, primarily VGI, and C. neoformans (19,21,23). There is also growing evidence that antifungal drug susceptibility may vary between geographical locations for the same molecular type (19,21,24).…”