Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterisation of Candida auris Detected in a Surveillance Program

Antimicrob Agents Chemother. 2021 Jan 11:AAC.02031-20. doi: 10.1128/AAC.02031-20. Online ahead of print.

ABSTRACT

A total of 15 Candida auris isolates from the SENTRY Antimicrobial Surveillance Program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed for genetic relatedness and resistance mechanisms. Applying the tentative statistical epidemiological cutoff values and the Centers for Disease Control tentative breakpoints, 32/36 isolates were resistant to fluconazole, 5/36 were resistant to amphotericin B, 5/36 were non-wildtype (NWT) to anidulafungin, 3/36 were NWT to micafungin, and 1/36 and 10/36 were non-WT to isavuconazole and voriconazole, respectively. Ten isolates were multidrug-resistant, which is when isolates are resistant to 2 antifungal classes. Synergy or partial synergy was noted in 5/36 and 22/36 of the isolates with the combination of anidulafungin plus voriconazole and 11/36 and 19/36 isolates for the combination of anidulafungin plus isavuconazole. MLST analysis of the 15 SENTRY isolates demonstrated that the isolates from the US were genetically related to, but different from isolates from Latin America (Panama and Colombia) and Germany. Single nucleotide polymorphism analysis showed that the 15 SENTRY isolates belonged to the described international clades and had associated Erg11 alterations, including 11 isolates displaying K143R, 1 F126L, 1 Y501H alterations, and fluconazole MIC results of ≥64 mg/L. Resistance mechanisms were not observed in the 2 isolates displaying fluconazole MIC values at 4 and 16 mg/L. Isavuconazole displayed activity and greater synergy when tested with anidulanfungin than seen with anidulafungin plus voriconazole against the C. auris clinical isolates that displayed resistance phenotypes.

PMID:33431416 | DOI:10.1128/AAC.02031-20