Aztreonam-Avibactam Shows Potent Activity Against Enterobacterales Isolates

Although the frequency of metallo-β-lactamase (MBL)- and OXA-48 type-producing Enterobacterales isolates is increasing, aztreonam-avibactam shows consistently potent activity against carbapenem-resistant Enterobacterales (CRE) isolates. These study results were published in Open Forum Infectious Diseases.

Researchers evaluated a total of 27,834 Enterobacterales isolates collected from 74 hospitals across 36 US states between 2019 and 2021. Isolates were screened for antimicrobial susceptibility via broth microdilution, and recent trends in resistant phenotypes were assessed.

Among the isolates included in the analysis, most (>99.9%) were inhibited by aztreonam-avibactam at a dose of 8 mg/L or more. Stratified by type, 99.2% of multidrug-resistant (MDR) organisms, 97.3% of CRE organisms, and 92.7% of extensively drug-resistant organisms were inhibited by aztreonam-avibactam at a dose of at least 2 mg/L.

The 3 isolates that were not inhibited were Escherichia coli (n=2) and Klebsiella aerogenes (n=1). The E coli isolates contained numerous mutations, including a bla_CMY transferrable cephalosporinases, similar mutations in the outer membrane porin C (OmpC) and penicillin-binding protein 2, and a YRIK insertion at Y333 in penicillin-binding protein 3. The K aerogenes isolate had multiple mutations in ampC β-lactamase and a truncated OmpC.

Further analysis was performed after stratification by year. Fewer isolates collected in 2021 vs 2019 were inhibited by ceftazidime-avibactam (99.7% vs 99.9%), meropenem-vaborbactam (99.7% vs 99.9%), ceftolozane-tazobactam (94.1% vs 95.0%), piperacillin-tazobactam (88.2% vs 89.2%), ceftriaxone (82.1% vs 84.0%), meropenem (98.8% vs 99.1%), gentamicin (88.5% vs 89.8%), and amikacin (93.7% vs 95.2%). Among only CRE isolates, the decreased rates observed in 2021 compared with 2019 were more pronounced for ceftazidime-avibactam (78.6% vs 92.5%) and meropenem-vaborbactam (76.5% vs 91.7%), respectively.

Stratified by infection type, the lowest susceptibility was observed for bloodstream infections (79.4%) and urinary tract infections (82.2%) treated with levofloxacin, as well as for pneumonia (75.3%) and skin and skin structure infections (82.3%) treated with ceftriaxone.

The frequencies of resistance genes were observed to change between 2019 and 2021. During this period, the rate of K pneumoniae carbapenemases-type mutations decreased from 73.8% to 57.1%, the rate of MBL-type mutations increased from 3.8% to 20.4%, and the rate of OXA-48-type mutations increased from 1.3% to 8.2%, respectively.

This study was limited as cefiderocol was not assessed, and some medical centers did not participate for the total study duration.

“Due to the clinical importance of these rapid fluctuations in the epidemiology of β-lactam resistance mechanisms, the results of comprehensive surveillance programs are critical to plan therapeutic strategies and infection control measures,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.