Choosing Optimal Antibiotics for the Treatment of Patients Infected With Enterobacteriaceae: A Network Meta-analysis and Cost-Effectiveness Analysis

Overuse of carbapenems has led to the increasing carbapenem-resistant Enterobacteriaceae. It is still unknown whether other antibiotics [especially novel beta-lactam/beta-lactamase inhibitor combinations (BL/BLIs)] are better than carbapenems in the treatment of Enterobacteriaceae. A systematic literature search was performed to identify randomized controlled trials (RCTs) assessing the efficacy and safety of any antibiotics on Enterobacteriaceae infections. We carried out a traditional paired meta-analysis to compare ceftazidime/avibactam to comparators. Network meta-analysis (NMA) was conducted to integrate direct and indirect evidence of all interventions. Moreover, cost-effectiveness analysis using a combined decision analytical Markov model was completed for the treatment of patients with complex urinary tract infection (cUTI). A total of 25 relevant RCTs were identified, comprising 15 different interventions. Ceftazidime/avibactam exhibited comparable efficacy and safety with comparators (carbapenems) in the paired meta-analysis. In the NMA, the surface under the cumulative ranking curve probabilities showed that in terms of efficacy, the interventions with the highest-ranking were meropenem/vaborbactam, meropenem, imipenem/cilastatin, ceftriaxone, ceftazidime/avibactam, and ceftolozane/tazobactam [but no significant difference between any two antibiotics (p > 0.05)]. Regarding safety, ceftazidime/avibactam had a higher incidence of adverse events than that of piperacillin/tazobactam (relative risk = 0.74, 95% confidence interval = 0.59-0.94). Based on drug and hospitalization costs in China, the incremental cost-effectiveness ratio per quality-adjusted life-year gained in the patients with cUTI for meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam compared to imipenem/cilastatin were US$579, US$24569, and US$29040, respectively. The role of these BL/BLIs to serve as alternatives to carbapenems requires large-scale and high-quality studies to validate.