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

• Main Authors: Ruiying Han (Author), Mengmeng Teng (Author), Ying Zhang (Author), Tao Zhang (Author), Taotao Wang (Author), Jiaojiao Chen (Author), Sihan Li (Author), Bo Yang (Author), Yaling Shi (Author), Yalin Dong (Author), Yan Wang (Author)
• Format: Book
• Published: Frontiers Media S.A., 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2021.656790
• Keywords: Enterobacteriaceae; network meta-analysis; complicated urinary tract infection; novel β-lactam/β-lactamase inhibitors; cost-effectiveness analysis; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 12 (2021)

Overuse of carbapenems has led to the increasing carbapenem-resistant Enterobacteriaceae. It is still unknown whether other antibiotics [especially novel β-lactam/β-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.