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

Chi Phuong Nguyen, Thuc Nguyen Dan Do, Roger Bruggemann, Jaap ten Oever, Eva Kolwijck, Eddy M.M. Adang, Heiman F.L. Wertheim

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)790-797
Number of pages8
JournalInternational Journal of Antimicrobial Agents
Volume54
Issue number6
DOIs
Publication statusPublished - Dec 2019
Externally publishedYes

Keywords

  • Carbapenem-sparing beta-lactams
  • Extended-spectrum beta-lactamase
  • Intra-abdominal infection
  • Meropenem
  • Urinary tract infection

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