Journal of Global Antimicrobial Resistance (Dec 2024)
In Vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenemase-producing Enterobacterales Collected in Turkey and the Middle East as Part of the ATLAS Surveillance Program: 2018-2022
Abstract
BACKGROUND: Aztreonam-avibactam is approved in the European Union for treatment of hospital/ventilator acquired bacterial pneumonia, complicated intraabdominal infection, complicated urinary tract infection and infections where treatment options are limited. Aztreonam is stable to hydrolysis by metallo-β-lactamases (MBLs), while avibactam inhibits class A and C β-lactamases, often co-carried by MBL-positive isolates, that inactivate aztreonam. This study examined the activity of aztreonam-avibactam and comparators against Enterobacterales carrying carbapenemases collected in 2018-2022 as part of the ATLAS surveillance program. METHODS: 6335 non-duplicate Enterobacterales isolates were collected from 17 medical centers in Israel, Jordan, Kuwait, Qatar, Saudi Arabia, and Turkey as part of the ATLAS program from 2018-2022. Susceptibility testing was by broth microdilution according to CLSI guidelines and interpreted according to EUCAST 2024 breakpoints. Organisms testing with meropenem MIC ≥2 mg/L or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, and Proteus mirabilis testing with ceftazidime or aztreonam MIC values ≥2 mg/L were screened for β-lactamase genes by PCR and Sanger sequencing. RESULTS: Of all 6335 isolates collected, 99.7% were susceptible to aztreonam-avibactam (MIC90=0.25 mg/L), more than any comparator agent tested (Table). Of isolates carrying any carbapenemase (n=577), 99.0% were susceptible to aztreonam-avibactam (MIC90=0.5 mg/L), which was also higher than for the comparators tested. Aztreonam-avibactam activity ranged from 97.9% - 100% against isolates carrying NDM (±OXA-48-like), OXA-48-like, or KPC, whereas the most active comparator (colistin) was active against 64.7-79.2% of these isolates. CONCLUSION: The potent in vitro activity of aztreonam-avibactam against carbapenemase-producing Enterobacterales highlights the importance of its medical need.
