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

Abstract

The purpose of this study is to evaluate the activities of aztreonam-avibactam and comparator agents againstEnterobacterales 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 (> 8mg/L) for aztreonam-avibactam were screened for β-lactamase-encoding genes by whole-genome sequencing. Aztreonam-avibactam inhibited 99.9% of Enterobacterales at ≤ 8mg/L (MIC50/90, ≤ 0.03/0.12mg/L) and retained potent activity against CRE (MIC50/90, 0.25/0.5mg/L), multidrug-resistant isolates (MDR; MIC50/90, 0.12/0.5mg/L), and extensively drug-resistant (XDR) isolates (MIC50/90, 0.25/0.5mg/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 blaKPC (36.3% of CRE), blaOXA-48 type (27.1% of CRE), and the MBLs (25.7% of CRE). All CPE producers were inhibited at an aztreonam-avibactam concentration of ≤ 8mg/L. Aztreonam-avibactam demonstrated potent activity across the evaluated geographic regions and infection types.