Servicio de Microbiología, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), CIBERINFEC, Palma de Mallorca, Spain.
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
J Antimicrob Chemother. 2022 Jun 29;77(7):1862-1872. doi: 10.1093/jac/dkac122.
To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU).
723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution. Horizontally acquired β-lactamases were analysed through phenotypic and genetic assays. The first respiratory isolates from 105 patients providing such samples were analysed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and the genetic basis of hypermutation were assessed.
All agents except colistin showed resistance rates above 20%, including ceftolozane/tazobactam and ceftazidime/avibactam. 24.9% of the isolates were XDR, with a wide intercountry variation (0%-62.5%). 13.2% of the isolates were classified as DTR (difficult-to-treat resistance). 21.4% of the isolates produced ESBLs (mostly PER-1) or carbapenemases (mostly NDM-1, VIM-1/2 and GES-5). WGS showed that these determinants were linked to high-risk clones (particularly ST235 and ST654). WGS revealed a wide repertoire of mutation-driven resistance mechanisms, with multiple lineage-specific mutations. The most frequently mutated genes were gyrA, parC, oprD, mexZ, nalD and parS, but only two of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91%-100%) and resistance (94%-100%) was documented.
An overall high prevalence of resistance is documented European ICUs, but with a wide intercountry variability determined by the dissemination of XDR high-risk clones, arguing for the need to reinforce infection control measures.
在一项前瞻性队列研究（ASPIRE-ICU）中，确定来自欧洲 ICU 的铜绿假单胞菌分离株的药敏谱和耐药组。
对来自 11 个国家 29 个地点的 402 名患者的呼吸道样本或肛周拭子的 723 株分离株进行了研究。通过肉汤微量稀释法测定 12 种抗生素的 MIC。通过表型和遗传检测分析水平获得的β-内酰胺酶。对 105 名提供此类样本的患者的第一批呼吸道分离株进行了 WGS 分析，包括耐药组分析和先前定义的基因型耐药评分。评估了自发突变频率和超突变的遗传基础。
除粘菌素外，所有药物的耐药率均高于 20%，包括头孢他啶/他唑巴坦和头孢噻肟/阿维巴坦。24.9%的分离株为 XDR，各国之间的差异很大（0%-62.5%）。13.2%的分离株被归类为 DTR（难治疗耐药）。21.4%的分离株产生 ESBLs（主要为 PER-1）或碳青霉烯酶（主要为 NDM-1、VIM-1/2 和 GES-5）。WGS 表明，这些决定因素与高危克隆（特别是 ST235 和 ST654）有关。WGS 揭示了广泛的突变驱动的耐药机制，具有多种谱系特异性突变。最常突变的基因是 gyrA、parC、oprD、mexZ、nalD 和 parS，但只有 2 株分离株是高突变性的。最后，记录了基因型评分预测敏感性（91%-100%）和耐药性（94%-100%）的良好准确性。
在欧洲 ICU 中记录了总体较高的耐药率，但由于 XDR 高危克隆的传播，各国之间的耐药率存在很大差异，这表明需要加强感染控制措施。
