Department of Pediatrics, Chonnam National University Medical School, Gwangju, South Korea.
Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Microbiol Spectr. 2024 Oct 3;12(10):e0088324. doi: 10.1128/spectrum.00883-24. Epub 2024 Aug 20.
The clonal transmission of fluconazole-resistant isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 . isolates, comprising 31 isolates from three premature infants with persistent bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles.
The prevalence of fluconazole-resistant bloodstream infections caused by is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of bloodstream infections within the same hospital, revealing the transmission of clonal strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy.
通过全基因组测序（WGS）对医院内氟康唑耐药株的克隆传播进行分析的情况很少见。我们对 79 株 进行了 WGS 分析，其中包括 2022 年在同一家新生儿重症监护病房（NICU）中接受抗真菌治疗但持续发生血流感染的 31 例早产儿中的 31 株，以及 2010 年至 2022 年期间来自韩国 15 家医院的 48 名患者的 48 株（27 株为氟康唑耐药且为氟康唑剂量依赖性敏感，21 株为氟康唑敏感）血流感染株。基于 WGS 单核苷酸多态性（SNP）的系统发育分析根据多位点序列分型（MLST）区分了 79 株（17 株 ST3、13 株 ST7、2 株 ST22、41 株 ST26、4 株 ST55 和 2 株 ST59 分离株），并揭示了 ST26 分离株中可能存在的两起医院内传播簇。来自 2022 年重叠 NICU 住院的两名早产儿的一个簇包含 15 株氟康唑耐药株，这些耐药株携带多药耐药转录因子（Pdr1p）P258L（13 株）或 N1086I（2 株），以及 10 株缺乏 Pdr1pSNP 的氟康唑剂量依赖性敏感株。另一个簇表明，在同一医院的 8 个月内，5 名患者（4 名肺移植后和 1 名弥漫性间质性肺病）之间存在意外的氟康唑耐药血流感染的克隆传播。这 5 株分离株中，4 株在接触唑类抗真菌药物后获得，携带不同的 Pdr1pSNP（N1091D、E388Q、K365E 和 R376Q）。这些发现揭示了接受抗真菌治疗的患者中 克隆血流分离株的传播模式，表现出不同水平的氟康唑敏感性或不同的 Pdr1pSNP 谱。
全球范围内由 引起的氟康唑耐药性血流感染的患病率正在上升，但医院内这些耐药菌株的传播情况很少被记录。通过全基因组测序和流行病学分析，本研究在同一医院内确定了两个潜在的 血流感染簇，揭示了具有不同氟康唑敏感性或不同转录因子多药耐药蛋白 1（Pdr1p）单核苷酸多态性谱的克隆 菌株在接受抗真菌治疗的患者中的传播。
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