Clinical cure rate and cost-effectiveness of carbapenem-sparing beta-lactams vs. meropenem for Gram-negative infections: A systematic review, meta-analysis, and cost-effectiveness analysis

The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of carbapenem resistance. Treatment success of carbapenem-sparing beta-lactams (CSBs) for ESBL infections is unclear. The aim of this study was to appraise the clinical cure rate and estimate the cost-effectiveness of meropenem vs. CSBs (piperacillin-tazobactam, temocillin, ceftazidime-avibactam, and ceftolozane-tazobactam) for urinary tract infections (UTIs) or intra-abdominal infections (IAIs) due to ESBL/AmpC-producing bacteria. A systematic literature search of the Cochrane library, EMBASE, PubMed, and Web of Science was conducted to identify studies assessing the clinical cure rate of the antibiotics. To assess the cost-effectiveness of CSBs vs. meropenem, a combined decision analytic and Markov model was probabilistically analysed over a 5-year period. The main outcome was presented as the incremental cost-effectiveness ratio and evaluated with a threshold of (sic)20 000 per life year gained (LYG). From 656 identified articles, 17 and 14 studies were included in the qualitative synthesis and quantitative synthesis, respectively. A clinical cure of ceftazidime-avibactam and ceftolozane-tazobactam was comparable to meropenem in patients with complicated IAIs (cIAIs) due to ESBL (Risk ratio [RR] = 1.04, 95% confidence interval [CI] = 0.95-1.13). Both temocillin and ceftolozane-tazobactam were deemed cost-effective compared to meropenem with (sic)157.58 and (sic)13 398.34 per LYG, respectively, in patients with UTIs due to ESBL. However, only ceftazidime-avibactam (plus metronidazole) was cost-effective for the treatment of IAIs, with (sic)16 916.77 per LYG. These results show that several CSBs can be considered as viable candidates for the treatment of UTIs and IAIs caused by ESBL. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.