Gene Mutation Prevalence in Triazole-Resistant Clinical Isolates.

Recently, mutations in the -encoding gene (), a gene involved in ergosterol production, were associated with triazole-resistance in . In this study, we determined the prevalence and characteristics of mutations in a collection of clinical triazole-resistant isolates collected during 2001-2019 from two international mycology reference centers: the Belgian National Reference Center for Mycosis and the Center of Expertise in Mycology Radboudumc/CWZ. Clinical isolates with and without gene mutations and randomly selected wild-type (WT) controls were included. Isolates were characterized by in vitro susceptibility testing, and sequencing, and short tandem repeat typing. Available clinical records were analyzed for previous triazole exposure. In 23 isolates (24%) of the 95 triazole-resistant isolates, gene mutations were observed; including 5/23 (22%) isolates without gene mutations and 18/72 (25%) with mutations. Four previously described gene mutations (E105K, G307R/D, G466V, and S541G) and two novel mutations (W273S and L304P) were found; 4/23 (17%) in the sterol-sensing-domain region. No triazole-antifungal exposure was reported in 75% (9/12) of patients harboring an isolate with gene mutations. Three of 39 WT isolates (8%) contained a gene mutation; E105K (2-isolates) and S541G. gene mutations were predominantly found in with mutations with voriconazole MICs ≥ 8 mg/L.