ABSTRACT

Purpose: to characterize the distribution and mechanisms involved in ceftolozane/tazobactam (C/T) resistance in Pseudomonas aeruginosa isolates recovered from intensive care units (ICUs) in Portugal as part of the STEP surveillance study. Materials and methods: a total of 226 P. aeruginosa isolates were collected from patients with low respiratory tract infections (LRTI) admitted to ICUs between June 2017 and July 2018. Susceptibility to antimicrobials including the recent C/T combination was determined by EUCAST-criteria. Whole genome sequencing (WGS) was performed in a subset of 17 isolates. Results: multidrug resistant (MDR) and extremely drug resistant (XDR) phenotypes accounted for 20.4% and 25.7% of cases, respectively. C/T showed the highest susceptibility rate in both MDR (100%) and XDR (93.1%) isolates, followed by amikacin (97.8% MDR and 79.3% XDR). bla_KPC-3 (n = 2) and bla_GES-13 (n = 1) carbapenemase genes were detected in 3 of the 17 sequenced isolates, but only the GES-13-producing isolate displayed resistance to C/T. Additionally, the C/T-resistant phenotype was also found in two non-carbapenemase producers that carried known ceftolozane/tazobactam resistance-associated mutations in the PBP3 gene. Conclusions: C/T was highly active against MDR/XDR-P. aeruginosa isolates causing LRTI in ICUs. Moreover, beyond carbapenemase-encoding genes, mutations in chromosomal PBP-encoding genes might also be involved in ceftolozane/tazobactam resistance in Portugal.

中文翻译：

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在葡萄牙从 ICU 患者的下呼吸道感染中恢复的铜绿假单胞菌的体外表征（STEP 研究）

摘要

目的：作为 STEP 监测研究的一部分，表征从葡萄牙重症监护病房 (ICU) 回收的铜绿假单胞菌分离株中头孢洛扎/他唑巴坦 (C/T) 耐药性的分布和机制。材料与方法：共226个铜绿假单胞菌从 2017 年 6 月至 2018 年 7 月期间入住 ICU 的下呼吸道感染 (LRTI) 患者中收集了分离株。 EUCAST 标准确定了对抗生素的敏感性，包括最近的 C/T 组合。在 17 个分离株的子集中进行了全基因组测序 (WGS)。结果：多重耐药（MDR）和极度耐药（XDR）表型分别占病例的20.4%和25.7%。C/T 在 MDR (100%) 和 XDR (93.1%) 分离株中显示出最高的易感性，其次是阿米卡星（97.8% MDR 和 79.3% XDR）。bla _KPC-3 ( n  = 2) 和bla _GES-13 ( n = 1) 在 17 个测序分离株中的 3 个中检测到碳青霉烯酶基因，但只有产生 GES-13 的分离株显示出对 C/T 的抗性。此外，还在两个非碳青霉烯酶生产者中发现了 C/T 抗性表型，它们在 PBP3 基因中携带已知的头孢噻吩/他唑巴坦抗性相关突变。结论：C/T 对 MDR/XDR-铜绿假单胞菌分离株在 ICU 中引起 LRTI具有高度活性。此外，除了碳青霉烯酶编码基因外，染色体 PBP 编码基因的突变也可能与葡萄牙的头孢噻吩/他唑巴坦耐药有关。