Antimicrobial activities of aztreonam-avibactam and comparator agents tested against Enterobacterales from European hospitals analysed by geographic region and infection type (2019-2020)

The purpose of this study is to evaluate the activities of aztreonam-avibactam and comparator agents against Enterobacterales isolates from European medical centres as well as the occurrence of carbapenemases (CPEs). A total of 11,655 Enterobacterales isolates were collected consecutively in 2019-2020 from 38 medical centres located in Western Europe (W-EU; n = 8,784; 25 centres in 10 countries) and the Eastern European and Mediterranean region (E-EU; n= 2,871; 13 centres in 10 countries). Isolates were susceptibility tested by broth microdilution methods in a monitoring laboratory. The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by geographic region and infection type. Isolates that showed resistance to carbapenems (CRE) and/or elevated MICs (> 8 mg/L) for aztreonam-avibactam were screened for beta-lactamase-encoding genes by whole-genome sequencing. Aztreonam-avibactam inhibited 99.9% of Enterobacterales at <= 8 mg/L (MIC50/90, <= 0.03/0.12 mg/L) and retained potent activity against CRE (MIC 50/90, 0.25/0.5 mg/L), multidrug-resistant isolates (MDR; MIC50/90, 0.12/0.5 mg/L), and extensively drug-resistant (XDR) isolates (MIC50/90, 0.25/0.5 mg/L). Susceptibility to comparator agents was consistently lower among isolates from E-EU compared to W-EU for all infection types evaluated. CRE rates varied from 0.6% (urinary tract infection [UTI]) to 2.3% (bloodstream infection) in W-EU, and from 6.1% (UTI) to 17.0% (pneumonia) in E-EU. A CPE-encoding gene was identified in 360 of 424 (84.9%) CRE isolates, and the most common CPEs were bla(KPC )(36.3% of CRE), bla(OXA-)(48 )type (27.1% of CRE), and the MBLs (25.7% of CRE). All CPE producers were inhibited at an aztreonam-avibactam concentration of <= 8 mg/L. Aztreonam-avibactam demonstrated potent activity across the evaluated geographic regions and infection types.

Automated summary

The study evaluated the activity of aztreonam-avibactam against Enterobacterales isolates from European medical centers and the occurrence of carbapenemases. The results showed that aztreonam-avibactam had high inhibitory activity against Enterobacterales isolates and retained potent activity against resistant strains. The study also found that isolates from the Eastern European and Mediterranean region had lower susceptibility to comparator agents compared to isolates from Western Europe.