Comparative Effectiveness of Carbapenems Versus Non-Carbapenem Regimens in Multidrug-Resistant Infections: A Systematic Review

Abstract

Objective:

To systematically review the comparative clinical effectiveness, safety, and resistance emergence of carbapenems versus non-carbapenem antibiotic regimens for treating multidrug-resistant (MDR) infections.

Methods:

A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and major clinical trial registries for studies published between 2018 and mid-2025. Included were randomized controlled trials (RCTs), meta-analyses, and large observational cohorts comparing carbapenem and non-carbapenem regimens in adults with MDR Gram-negative infections. Outcomes extracted comprised clinical cure, microbiological eradication, mortality, adverse events, and resistance rates. Quality assessment utilized Cochrane and Newcastle-Ottawa tools.

Results:

Thirty-one studies (including 17 RCTs, 9 meta-analyses, and 5 large cohort studies) met inclusion criteria. Both carbapenem and non-carbapenem regimens demonstrated similar overall effectiveness for mortality and clinical cure, with non-carbapenem options (especially beta-lactam/beta-lactamase inhibitors and new cephalosporins) providing comparable outcomes in urinary, respiratory, and bloodstream infections when susceptible. Combination therapy may confer increased survival for carbapenemase-producing organisms but requires further high-quality trial data. Resistance emergence was lower with carbapenem-sparing regimens; safety profiles were similar.

Conclusion:

Non-carbapenem regimens represent a viable alternative to carbapenems for many MDR infections, supporting stewardship efforts to preserve carbapenem efficacy. Regimen choice should be individualized based on microbiologic susceptibility, infection site, and clinical severity.