Cefmetazole or flomoxef versus carbapenems in treating patients with extended-spectrum β-lactamase-producing Enterobacterales bacteremia: A systematic review and meta-analysis.

BACKGROUND

Cefmetazole and flomoxef are alternative therapies for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) bacteremia in Asia; however, their comparative efficacy remains unclear. We evaluated their efficacy versus carbapenems in adults with ESBL-PE bacteremia.

METHODS

We conducted a systematic review and meta-analysis of targeted therapy for ESBL-PE bacteremia in adults. Primary outcomes were 14-day and 30-day mortality. Odds ratios (ORs) were pooled using fixed- and random-effects models.

RESULTS

Ten studies (975 patients) were included. Fourteen-day mortality (5 studies) was significantly higher in the cefmetazole/flomoxef group than in the carbapenem group (fixed-effect OR: 2.32; 95% CI: 1.24-4.35; I2 = 30%), primarily driven by flomoxef in high-risk populations. Conversely, 30-day mortality (6 studies), largely reflecting cefmetazole use, showed no significant difference between groups (fixed-effect OR: 1.12; 95% CI: 0.71-1.75; I2 = 69%). Subgroup analyses revealed flomoxef was associated with increased 14-day mortality (OR: 2.50; 95% CI: 1.32-4.73), whereas cefmetazole was associated with decreased 30-day mortality (OR: 0.34; 95% CI: 0.14-0.84) versus carbapenems. However, cefmetazole results may have been influenced by treatment-selection bias, including lower baseline severity and more controllable infection foci.

CONCLUSIONS

The clinical impacts of cefmetazole and flomoxef varied by agent and clinical context. Flomoxef was associated with increased 14-day mortality in high-risk populations, whereas overall 30-day mortality with cefmetazole did not differ significantly from carbapenems after accounting for clinical heterogeneity. Given this variability, a unified effect cannot be determined. Randomized controlled trials stratified by agent and disease severity are needed to evaluate their potential as carbapenem-sparing therapies.