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

Int J Antimicrob Agents. 2019 Dec;54(6):790-797. doi: 10.1016/j.ijantimicag.2019.07.003. Epub 2019 Jul 5.

Abstract

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 €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 €157·58 and €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 €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.

Keywords: Carbapenem-sparing beta-lactams; Extended-spectrum beta-lactamase; Intra-abdominal infection; Meropenem; Urinary tract infection.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / classification
  • Anti-Bacterial Agents / economics*
  • Anti-Bacterial Agents / therapeutic use*
  • Cost-Benefit Analysis*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Humans
  • Meropenem / classification
  • Meropenem / economics
  • Meropenem / therapeutic use*
  • beta-Lactams / classification
  • beta-Lactams / economics
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Meropenem