RESUMO
Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006–2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1 , MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.
RESUMO
BACKGROUND: Candida auris was first isolated from the ears of Japanese and Korean patients. However, the prevalence of yeast isolates from ear cultures and their antifungal susceptibility profiles in these nations remain unclear.METHODS: We assessed yeast isolates recovered from ear cultures from a university hospital in Korea over a 4-year period from January 2014 to December 2017. Species identification was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and/or sequence analysis. Antifungal minimal inhibitory concentrations (MICs) were determined using the broth microdilution method of the Clinical and Laboratory Standards Institute.RESULTS: Among 81 non-duplicate isolates from ear cultures, Cadida parapsilosis was the most frequently detected yeast species (34.6%), followed by C. auris (28.4%), Candida metapsilosis (9.9%), Candida orthopsilosis (8.6%), Candida albicans (7.4%), and others (11.1%). The MICs of the isolates were 0.125 to > 64 µg/mL, ≤0.03 to 4 µg/mL, 0.25 to 1 µg/mL, 0.125 to 1 µg/mL, and ≤0.03 to 2 µg/mL for fluconazole, voriconazole, amphotericin B, caspofungin, and micafungin, respectively. Of the 81 isolates, 44.4% (36/81) showed decreased susceptibility to fluconazole (MIC ≥4 µg/mL). Of the 23 C. auris isolates, 19 (82.6%) had a fluconazole MIC of ≥32 µg/mL. None of the isolates showed resistance to amphotericin B or echinocandins. Most of these patients suffered from chronic otitis media (84%).CONCLUSION: Candida parapsilosis complex and C. auris were the yeast species identified most frequently from ear cultures and they exhibited a high rate of fluconazole non-susceptibility, particularly C. auris.