The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?

• Published in: Clinical infectious diseases 2024-10, Vol.79 (4), p.834
• Main Authors: Aitken, Samuel L, Pierce, Virginia M, Pogue, Jason M, Kline, Ellen G, Tverdek, Frank P, Shields, Ryan K
• Format: Article
• Language: English
• Subjects: Aged; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Azabicyclo Compounds - pharmacology; Azabicyclo Compounds - therapeutic use; Aztreonam - pharmacology; beta-Lactamase Inhibitors - pharmacology; beta-Lactamase Inhibitors - therapeutic use; beta-Lactamases - genetics; beta-Lactamases - metabolism; Cefiderocol; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Drug Combinations; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli Infections - drug therapy; Escherichia coli Infections - microbiology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Penicillin-Binding Proteins - genetics; Penicillin-Binding Proteins - metabolism; United States
• ISSN: 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciae229

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.