Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific

Abstract

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 2017-2020 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 (MIC_50/90, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC_50/90, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC_50/90, 0.5/8 mg/L). Voriconazole (MIC_50/90, >8/>8 mg/L) and the echinocandins (MIC_50/90, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27; MIC_50/90, 1/>8 mg/L), Lichtheimia spp. (n = 11; MIC_50/90, 4/8 mg/L), and Mucor spp. (n = 8; MIC₅₀, >8 mg/L) isolates, respectively. Posaconazole MIC_50/90 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 MIC_50/90 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.

Keywords: Lichtheimia; Rhizomucor; Rhizopus; antifungal activity; azoles; mucormycosis.

Figure 1

Distribution of Mucorales isolates recovered from invasive fungal infections worldwide (2017–2020). PIHP, pneumonia in hospitalized patients; SSSI, skin and skin structure infection; IAI, intra-abdominal infection.