Comparative efficacy and safety of carbapenems vs noncarbapenem antibiotics in AmpC-producing Enterobacterales infections: A systematic review and meta-analysis

OBJECTIVES: This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems vs noncarbapenem antibiotics in adult hospitalized patients with AmpC-producing Enterobacterales infections across various infection sites. METHODS: A comprehensive search of PubMed, Embase, and Cochrane Library databases was conducted for observational studies and randomized controlled trials comparing carbapenems with alternative agents. Primary outcomes included 30-day all-cause mortality, microbiological failure, infection recurrence, and adverse drug reactions (ADRs). RESULTS: Seventeen studies met the inclusion criteria. There was no significant difference in 30-day mortality (odds ratio [OR] = 1.29; 95% CI: 0.91-1.82; P = 0.16) or infection recurrence (OR = 0.98; 95% CI: 0.32-2.97; P = 0.97) between carbapenems and noncarbapenems. Microbiological failure rates were also comparable. However, carbapenems were associated with a higher incidence of ADRs (OR = 4.32; 95% CI: 1.73-10.79; P = 0.03). Clinical success trended in favor of noncarbapenem agents, though the difference did not reach statistical significance (OR = 0.56, 95% CI: 0.29-1.08; P = 0.08). CONCLUSION: While carbapenems remain effective for AmpC-producing infections, noncarbapenem alternatives offer comparable outcomes with fewer adverse events. These findings support IDSA guidance recommending agents such as cefepime when the minimum inhibitory concentration is ≤2 µg/ml and highlight the need for individualized, susceptibility-guided therapy.