Efficacy and Safety of Various Antibiotics in Bacteremia Caused by AmpC-Producing Enterobacteriaceae, Comparing Carbapenems: A Systematic Review and Network Meta-analysis

This meta-analysis aimed to evaluate the efficacy and safety of various antibiotics used as definitive therapy for bacteremia caused by AmpC-producing bacteria. MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to identify all relevant studies. Carbapenem served as a reference, and the intervention effects of the other antibiotics were compared. Primary outcomes were all-cause mortality, recurrent infections, and adverse events. A frequentist network meta-analysis was performed using a random-effects model to account for any significant heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (CIs) for each outcome in comparison with the carbapenem antibiotic were calculated based on the size of the population. Twelve studies were included in this meta-analysis. There were no significant differences in all-cause mortality or recurrent infections between carbapenems and other individual antibiotics. While cefepime significantly reduced the risk of adverse events compared to carbapenem (OR 0.28, 95% CI 0.14-0.57), and piperacillin-tazobactam showed a tendency to increase the risk of adverse events compared to carbapenem (OR 13.41, 95% CI 0.64-280.80). In conclusion, this meta-analysis found that cefepime was associated with comparable efficacy and fewer adverse events than carbapenems in the treatment of bacteremia caused by AmpC-producing bacteria. Additionally, potential concerns identified regarding the therapeutic efficacy of piperacillin-tazobactam, cephalosporins (excluding cefepime), fluoroquinolones, and aminoglycosides.