New-generation antibiotics and nonantibiotic strategies against carbapenemase-producing Enterobacterales: More focus on metallo-β-lactamase producers.
Journal
International Journal of Antimicrobial Agents
Journal Volume
67
Journal Issue
5
Start Page
Article Number : 107750
ISSN
1872-7913
Date Issued
2026-02-20
Author(s)
Abstract
Purpose Among various carbapenemase-producing Enterobacterales (CPE), strains producing metallo-β-lactamases (MBLs)—particularly New Delhi MBL (NDM)—exhibit the most severe resistant phenotypes. This study aimed to identify effective antibiotics or non-antibiotic agents against MBL-producing Enterobacterales. Methods An extensive literature search of Google Scholar and the PubMed database was conducted for articles published during 2010–2025 using the search terms (novel antibiotics OR phage) AND (MBL) AND (Enterobacterales OR Enterobacteriaceae). Results Cefiderocol exhibited lower susceptibility rates compared to aztreonam–avibactam against NDM-producing Enterobacterales isolates according to the 2025 European Committee on Antimicrobial Susceptibility Testing guidelines. Among novel β-lactamase inhibitors, taniborbactam (TAN), xeruborbactam (XER), zidebactam (ZID), and ANT2681 have demonstrated activity against MBLs. Nacubactam (NAC), when combined with partner β-lactams, is active in vitro against CPE isolates harboring bla NDM genes. TAN, XER, ZID, NAC, and ANT2681 are being developed in combination with meropenem, or cefepime for the treatment of infections caused by CPE, including various MBL producers. Additionally, due to the availability of both oral and parenteral formulations, regimens such as XER paired with ceftibuten or tebipenem are currently under evaluation for the treatment of infections caused by serine carbapenemase- and MBL-producing Enterobacterales. Moreover, the novel monobactam LYS228 alone has also demonstrated good in vitro potency against MBL producers. Novel polymyxin derivatives—including SPR741 (combined with mecillinam), SPR206, and QPX9003—and bacteriophages have shown promising activity against MBL-producing Enterobacterales. Conclusions Continued monitoring of resistance trends and the development of innovative therapeutic strategies is warranted in the ongoing battle against CPE harboring bla MBL.
Subjects
LYS228
Nacubactam
New Delhi metallo-β-lactamases
Taniborbactam
Xeruborbactam
Zidebactam
Publisher
Elsevier B.V.
Type
review