The following is a summary of “Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022),” published in the January 2025 issue of Pulmonology by Sader et al.
Antimicrobial therapy for pneumonia is often initiated empirically, and resistance to antimicrobial agents poses a significant challenge in treating hospitalized patients with pneumonia.
Researchers conducted a retrospective study to evaluate the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals.
They collected bacterial isolates (1 per patient) from individuals hospitalized with pneumonia across 69 medical centers (2020–2022). The antimicrobial susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was tested using broth microdilution in a monitoring lab. Aztreonam-avibactam was tested with fixed avibactam (4 mg/L) and a pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L. Carbapenem-resistant Enterobacterales (CRE) isolates (MIC > 2 mg/L for imipenem/meropenem) were screened for carbapenemases using whole genome sequencing.
The results showed Gram-negative bacilli comprised 71.1% of organisms, with Pseudomonas aeruginosa (22.4%) and Klebsiella pneumoniae (8.8%) most common and Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L, displaying potent activity against CRE (MIC50/90: 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were effective against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam also retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam/meropenem-vaborbactam (n = 19; MIC50/90: 0.25/4 mg/L). Common carbapenemases were KPC (69.2%), NDM (9.6%), and SME (4.8%), with no carbapenemase gene identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were effective against KPC/SME producers but limited against MBL producers. Tigecycline (95.2%), amikacin (73.1%), and gentamicin (60.6%) were the most active against CRE. Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L by aztreonam-avibactam, with 77.2% meropenem- and piperacillin-tazobactam-susceptible. Aztreonam-avibactam inhibited 99.5% of S. maltophilia isolates at ≤ 8 mg/L.
Investigators concluded the aztreonam-avibactam demonstrated strong in vitro activity against a wide range of contemporary Gram-negative organisms, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam.
Source: bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-025-03500-8