Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
2023
Cecilia G. Carvalhaes | Paul R. Rhomberg | Michael D. Huband | Michael A. Pfaller | Mariana Castanheira
Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017&ndash:2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC50/90, 2/>:8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at &le:2 mg/L and &le:4 mg/L, respectively. Among comparators, amphotericin B (MIC50/90, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC50/90, 0.5/8 mg/L). Voriconazole (MIC50/90, >:8/>:8 mg/L) and the echinocandins (MIC50/90, >:4/>:4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at &le:4 mg/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27: MIC50/90, 1/>:8 mg/L), Lichtheimia spp. (n = 11: MIC50/90, 4/8 mg/L), and Mucor spp. (n = 8: MIC50, >:8 mg/L) isolates, respectively. Posaconazole MIC50/90 values against Rhizopus, Lichtheimia, and Mucor species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively: amphotericin B MIC50/90 values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.
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