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.

中文翻译：

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韩国多中心监测研究中回收的氟康唑非敏感白色念珠菌血流分离株的分子和临床特征。

白色念珠菌血流感染 (BSI) 分离株中获得性氟康唑耐药 (FR) 的情况很少见。我们研究了2006-2021 年韩国多中心监测研究中回收的14 株氟康唑不敏感（FNS；FR 和氟康唑敏感剂量依赖性）BSI白色念珠菌BSI 分离株的 FR 机制和临床特征。导致药物靶基因ERG11和 FR 相关转录因子基因TAC1、MRR1和UPC2中氨基酸取代 (AAS) 的突变将 14 株 FNS 分离株与 12 株氟康唑敏感分离株进行比较。在 14 个 FNS 分离株中，8 个和 7 个分别具有 Erg11p（K143R、F145L 或 G464S）和 Tac1p（T225A、R673L、A736T 或 A736V）AAS，这在 FR 分离株中已有描述。分别在 2 个、4 个和 1 个 FNS 分离株中观察到新型 Erg11p、Tac1p 和 Mrr1p AAS。在 7 个 FNS 分离株中观察到合并的 Erg11p 和 Tac1p AAS。未检测到任何与 FR 相关的 Upc2p AAS。14 例患者中，仅 1 例既往有唑类暴露史，30 天死亡率为 57.1%（8/14）。我们的数据表明，Erg11p 和 Tac1p AAS 可能会导致韩国白色念珠菌BSI 分离株的 FR，并且大多数 FNS白色念珠菌BSI 在没有唑类暴露的情况下发生。