Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis. (6th April 2018)

• Record Type: Journal Article
• Authors: Sternbach, Neta; Leibovici Weissman, Yaara; Avni, Tomer; Yahav, Dafna
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 8(2018)
• Page Start: 2021
• Page End: 2029
• Publication Date: 2018-04-06
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky124
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Ceftazidime/avibactam is approved for complicated intra-abdominal and urinary tract infections (UTIs) based on results from randomized controlled trials (RCTs). Data regarding its effectiveness in treating hospital-acquired infections or resistant pathogens have not been systematically compiled. Methods: A systematic review and meta-analysis including RCTs evaluating ceftazidime/avibactam versus comparator for the treatment of any infection. Primary outcome was 30 day all-cause mortality. Subgroups of hospital-acquired infections and specific resistance phenotypes were planned. Results: Seven publications (eight trials, 4093 patients) were included, reporting a baseline ∼25% of ESBL-carrying Enterobacteriaceae. No significant difference between ceftazidime/avibactam and comparator (mostly carbapenem) was demonstrated for 30 day all-cause mortality, late follow-up mortality and clinical response [relative risk (RR) 1.10, 95% CI 0.70–1.72, P = 0.69; RR 1.23, 95% CI 0.87–1.76, P = 0.25; RR 0.98, 95% CI 0.96–1.01, P = 0.21, respectively, without significant heterogeneity]. Higher microbiological response rate was demonstrated with ceftazidime/avibactam in patients with UTI (RR 1.14, 1.0–1.29, P = 0.05, I 2 = 51%). No significant difference in clinical response was demonstrated for patients with ceftazidime-resistant pathogens (RR 1.02, 95% CI 0.94–1.10, P = 0.66, I 2 = 0%). Results for other subgroups of resistant pathogens or hospital-acquired infection were not available. Serious adverse events (SAEs) were significantly more common with ceftazidime/avibactam (RR 1.24, 95% CI 1.00–1.54, P = 0.05, I 2 = 0%). Conclusions: Ceftazidime/avibactam is clinically and microbiologically as effective as carbapenems for treatment of infections in a setting of ∼25% ESBL-carrying Enterobacteriaceae. Safety of the drug should be further evaluated owing to a higher rate of SAEs compared with carbapenems. Further studies should assess the drug's effectiveness in the treatment of carbapenemase-producing Enterobacteriaceae.