Department of Oncology and Emato-Oncology, University of Milan, Milan, Italy.
Microbiology and Virology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Ann Clin Microbiol Antimicrob. 2024 Nov 29;23(1):104. doi: 10.1186/s12941-024-00763-7.
During prolonged FDC therapy, the emergence of FDC non-susceptibility in CRAB has been reported. Here, we report a transmission cluster of FDC-non-susceptible CRAB in four patients, all naïve to FDC treatment, characterized by a premature stop codon and amino acid deletion in the PirA protein.
CRAB strains obtained from patients admitted in a single medicine ward of the IRCCS Fondazione Ospedale Maggiore Policlinico between March and July 2024 were analyzed by WGS and antimicrobial susceptibility testing. Phylogenetic analysis was used to assess their genetic relatedness.
Between March and July 2024, an outbreak of 33 CRAB was observed among hospitalized patients in a single ward at IRCCS. Genomic analysis, available in 29 cases, revealed that 24 isolates belonged to ST208/1806, 4 to ST369, and one to ST195/1816 (according to the Oxford scheme). FDC susceptibility was affected only in the four ST369 isolates (Kirby-Bauer disk diffusion diameter: 13 mm; UMIC method MIC: 4 mg/L), all characterized by a premature stop codon followed by a 52 amino acid deletion located between the amino acids 377 and 428 of the siderophore-drug receptor PirA. No other relevant mutations were detected in the iron-uptake genes. Core-genome ML tree including ST369 reference strains revealed that the four ST369 isolates were highly related and formed a distinct cluster (SNP distance: 3 [IQR: 1-6]). Of note, the four isolates were collected from four FDC-naïve individuals, two experiencing a CRAB-mediated infection.
Our findings alert about the circulation of clones carrying modified siderophore-drug receptors without evidence of previous FDC treatment and support the importance of testing FDC susceptibility appropriately before its administration.
在长期 FDC 治疗期间，已报道出现对 FDC 不敏感的 CRAB。在此，我们报告了在四名对 FDC 治疗无经验的患者中发生的 FDC 不敏感的 CRAB 传播集群，其特征在于在 PirA 蛋白中存在提前终止密码子和氨基酸缺失。
对 2024 年 3 月至 7 月期间在 IRCCS Fondazione Ospedale Maggiore Policlinico 的一个单一医学病房住院的患者获得的 CRAB 菌株进行 WGS 和抗菌药物敏感性测试分析。采用系统进化分析来评估它们的遗传相关性。
2024 年 3 月至 7 月期间，IRCCS 的一个单一病房住院患者中观察到 33 例 CRAB 爆发。对 29 例可进行基因组分析的病例显示，24 株分离株属于 ST208/1806，4 株属于 ST369，1 株属于 ST195/1816（根据牛津方案）。只有 4 株 ST369 分离株（Kirby-Bauer 纸片扩散直径：13mm；UMIC 方法 MIC：4mg/L）的 FDC 敏感性受到影响，均具有位于铁载体-药物受体 PirA 的氨基酸 377 和 428 之间的提前终止密码子和 52 个氨基酸缺失。在铁摄取基因中未检测到其他相关突变。包括 ST369 参考菌株的核心基因组 ML 树表明，这 4 株 ST369 分离株高度相关，形成了一个独特的聚类（SNP 距离：3[IQR：1-6]）。值得注意的是，这 4 株分离株来自 4 名对 FDC 无经验的个体，其中 2 名患有 CRAB 介导的感染。
我们的研究结果提醒人们注意携带修饰的铁载体-药物受体的克隆的传播，而没有先前 FDC 治疗的证据，并支持在使用 FDC 之前适当测试其敏感性的重要性。
