Aztreonam/avibactam activity against Enterobacterales from European medical centres: summary of 5 years of surveillance prior to approval for clinical use (2019–2023)

Abstract Objectives To evaluate the in vitro activity of aztreonam/avibactam against Enterobacterales from European medical centres during the 5-year period prior to its approval for clinical use in Europe. Methods Thirty thousand seventy-four Enterobacterales isolates were consecutively collected in 2019–2023 from 19 medical centres in Eastern Europe and Mediterranean region (E-EU; n = 8074) and 27 medical centres in Western Europe (W-EU; n = 22 000) and susceptibility tested by broth microdilution. Carbapenem-resistant Enterobacterales (CRE) and isolates with elevated MICs (>4 mg/L) for aztreonam/avibactam were molecularly characterized. Results Aztreonam/avibactam was active against 99.8% and >99.9% of Enterobacterales from E-EU and W-EU, respectively and exhibited potent activity against CRE isolates (MIC50/90, 0.25/0.5 mg/L; 99.6%/99.7% susceptible in E-EU/W-EU). Cefiderocol was active against 74.8%/87.6% of CREs from E-EU/W-EU. Ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam retained moderate activity against CRE isolates from W-EU (68.3–80.3% susceptibility) but showed limited activity against CRE isolates from E-EU (45.1–63.0% susceptible). The occurrence of carbapenemases varied markedly among the countries evaluated. In general, the MBLs predominated in E-EU and the KPCs prevailed in W-EU. Decreased susceptibility to aztreonam/avibactam was predominantly due to PBP3 alterations and production of CMY and/or CTX-M β-lactamases among Escherichia coli, and hyperexpression of ampC plus porin alterations in Enterobacter cloacae species complex and Klebsiella aerogenes. Conclusions The results of this investigation provide a valuable benchmark for monitoring the in vitro activity of aztreonam/avibactam after its clinical approval in Europe and emphasizes the importance of comprehensive surveillance programmes to monitor the emergence of high-risk clones and resistance mechanisms to newly approved antimicrobial agents.