Objective: To determine the susceptibility profiles and the resistome of P. aeruginosa isolates from European ICUs during a prospective cohort (ASPIRE-ICU).
Methods: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs for 12 antibiotics were determined by broth microdilution. Horizontally-acquired β27 lactamases were analyzed through phenotypic and genetic assays. The first respiratory isolate from 105 patients providing such samples were analyzed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and genetic basis of hypermutation were assessed.
Results: 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 2 of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91-100%) and resistance (94-100%) was documented.
Conclusions: 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 of reinforcement of infection control measures.
