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The following is a summary of “Antimicrobial susceptibility of enterobacterales causing bloodstream infection in United States medical centres: comparison of aztreonam-avibactam with beta-lactams active against carbapenem-resistant enterobacterales,” published in the November 2024 issue of Infectious Disease by Sader et al. 

Bloodstream infection (BSI) caused by multidrug-resistant Enterobacterales, including those producing metallo-β-lactamases (MBL) and OXA-48-like carbapenemases, are associated with poor outcomes. Aztreonam-avibactam, a novel antimicrobial combination, is under investigation for the treatment.  

Researchers conducted a retrospective study to evaluate the antimicrobial susceptibility of Enterobacterales causing BSIs in US medical centers and compare the activity of aztreonam-avibactam with other antimicrobials, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and others.  

They collected 4,802 Enterobacterales isolates (1/patient) from 72 US medical centers between 2020 and 2022 and tested their susceptibility using broth microdilution. Aztreonam-avibactam was tested with a fixed avibactam concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase-encoding genes using Next-generation sequencing.  

The results showed that aztreonam-avibactam was highly active against Enterobacterales, with only 2 isolates (1 meropenem-susceptible E. coli and 1 K. aerogenes CRE) resistant. All carbapenemase producers and 98.0% of CRE were susceptible to aztreonam-avibactam, CRE susceptibility rates were lower for other agents, with cefiderocol showing the highest activity (87.8%). Aztreonam-avibactam maintained activity against most non-susceptible isolates of other agents. The most common carbapenemases were KPC-2/3 (57.1%), OXA-48-like (16.3%), and NDM (14.3%). Carbapenemase genes were not detected in 12.3% of CREs. While ceftazidime-avibactam and meropenem-vaborbactam were active against KPC producers, they had limited activity against MBL and OXA-48-like producers. Gentamicin and amikacin were the most active non-β-lactam agents against CRE.  

Investigators concluded that aztreonam-avibactam exhibited potent activity against a diverse collection of Enterobacterales, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations. 

Sources: bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10133-5