Emerging resistance to imipenem-relebactam among enterobacterales and non-fermenting gram-negative bacilli: a systematic review and meta-analysis.

BACKGROUND

Multidrug-resistant Gram-negative bacteria (GNB), including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, pose a growing global health threat with limited treatment options. Imipenem-relebactam (IMI/REL) is a promising therapy, but emerging resistance patterns remain poorly defined worldwide.

OBJECTIVES

This meta-analysis aimed to provide a comprehensive assessment of global IMI/REL resistance among Enterobacterales and non-fermenting GNB, highlighting species-specific, geographic, and temporal patterns.

METHODS

Studies were searched in Scopus, PubMed, and EMBASE (until October 23 2024), and all statistical analyses were conducted using R (ver. 4.2.1).

RESULTS

A total of 149,396 Enterobacterales and non-fermenting GNB were included. Overall, IMI/REL resistance was low at 8.8% (95% CI 7.3-10.5), with Enterobacterales showing the lowest resistance (2.9%) and Pseudomonas the highest (30.7%). Resistance was higher in carbapenemase-producing Enterobacterales and non-fermenting species, and varied by infection source and geography. Temporal analysis indicated a rising trend in resistance over recent years, while data were mostly derived from the Americas, limiting global generalizability.

CONCLUSION

IMI/REL remains largely effective against Enterobacterales, including ESBL and MDR strains, but resistance is increasing in high-risk subgroups and non-fermenting bacteria. These findings underscore the need for local susceptibility testing, cautious empiric therapy, and robust antimicrobial stewardship to preserve the efficacy of IMI/REL.