Emerg Infect Dis. 2021 Mar;27(3):779-788. doi: 10.3201/eid2703.203482.
We investigated the clinical outcomes and molecular mechanisms of fluconazole-resistant (FR) bloodstream infections. Among 1,158 isolates collected during multicenter studies in South Korea during 2008–2018, 5.7% were FR. For 64 patients with FR bloodstream infection isolates, the 30-day mortality rate was 60.9% and the 90-day mortality rate 78.2%; these rates were significantly higher than in patients with fluconazole-susceptible dose-dependent isolates (30-day mortality rate 36.4%, 90-day mortality rate 43.8%; p<0.05). For patients with FR isolates, appropriate antifungal therapy was the only independent protective factor associated with 30-day (hazard ratio 0.304) and 90-day (hazard ratio 0.310) mortality. Sequencing of pleiotropic drug-resistance transcription factor revealed that 1–2 additional Pdr1p amino acid substitutions (except genotype-specific Pdr1p amino acid substitutions) occurred in 98.5% of FR isolates but in only 0.9% of fluconazole-susceptible dose-dependent isolates. These results highlight the high mortality rate of patients infected with FR . BSI isolates harboring Pdr1p mutations.
我们研究了氟康唑耐药（FR）血流感染的临床结果和分子机制。在 2008 年至 2018 年期间，韩国多中心研究中收集的 1158 株分离株中，有 5.7%是 FR。对于 64 例 FR 血流感染分离株患者，30 天死亡率为 60.9%，90 天死亡率为 78.2%；这些比率明显高于氟康唑敏感剂量依赖性分离株患者（30 天死亡率为 36.4%，90 天死亡率为 43.8%；p<0.05）。对于 FR 分离株患者，适当的抗真菌治疗是唯一与 30 天（危险比 0.304）和 90 天（危险比 0.310）死亡率相关的独立保护因素。多药耐药转录因子的测序显示，在 98.5%的 FR 分离株中发生了 1-2 个额外的 Pdr1p 氨基酸取代（除了特定基因型的 Pdr1p 氨基酸取代），而在仅 0.9%的氟康唑敏感剂量依赖性分离株中发生了这些取代。这些结果突出了携带 Pdr1p 突变的 FR 血流感染患者的高死亡率。
