Work

In vitro activities of aztreonam/nacubactam and cefepime/nacubactam against a global collection of molecularly characterized Enterobacterales isolates carrying carbapenemases: a global antimicrobial resistance surveillance study from 2021 to 2023

Year: 2026

Type: article

Abstract: Objectives Nacubactam is a novel diazabicyclooctane β-lactamase inhibitor with activity against PBP2 that is in clinical development with aztreonam or cefepime. The in vitro activities of aztreonam/nacubactam, cefepime/nacubactam and comparator agents were determined against carbapenemase-producing Enterobacterales, collected globally from 2021 to 2023. Methods Isolates were collected as part of a surveillance study from 24 countries in Asia, Europe and North America. Susceptibility testing was by CLSI broth microdilution. Meropenem-non-susceptible Enterobacterales isolates were sequenced by nanopore technology to identify resistance mechanisms. Of 12 613 isolates collected, 630 carbapenemase-producing isolates were detected. Results All KPC-producing (158) and OXA-48-like–producing (142) isolates were inhibited by ≤4/4 mg/L of aztreonam/nacubactam or ≤8/8 mg/L cefepime/nacubactam. Aztreonam/nacubactam at ≤4/4 mg/L was active against 98.7% of the 307 NDM-producing isolates, more than aztreonam/avibactam (95.1% susceptible) or cefiderocol [85.7% susceptible (CLSI breakpoints)], while cefepime/nacubactam was active against 94.1% at ≤8/8 mg/L. Insertions in PBP3 were present in 39/47 (83%) of NDM-positive Escherichia coli. Aztreonam/nacubactam was active against 97.4% of these at ≤4/4 mg/L and cefepime/nacubactam was active against 100% at ≤8/8 mg/L, while aztreonam/avibactam and cefiderocol activities were relatively poor [69.2% aztreonam/avibactam-susceptible and 46.2% cefiderocol-susceptible (CLSI)]. Conclusions Aztreonam/nacubactam and cefepime/nacubactam demonstrated potent in vitro activity against Enterobacterales that carried serine-carbapenemases and MBLs, including those with chromosomal resistance mechanisms that compromise the current best-in-class β-lactam antibiotics for treating infections caused by MBL-positive organisms. The percentage of NDM-positive E. coli with insertions in PBP3 is alarming and warrants continued surveillance.

Source: JAC-Antimicrobial Resistance

DOI: 10.1093/jacamr/dlag166

Authors: Mark Estabrook, Eisuke Suzuki, Atsuyuki Shimizu, Hayato Okade

Institution: Meiji Seika Pharma Co., Ltd. (Japan)

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Microbiology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,609