Evaluation of the efficacy and safety of ceftazidime/avibactam in the treatment of Gram-negative bacterial infections: a systematic review and meta-analysis

Int J Antimicrob Agents. 2018 Oct;52(4):443-450. doi: 10.1016/j.ijantimicag.2018.07.004. Epub 2018 Aug 31.

Abstract

Data on the efficacy and safety of ceftazidime/avibactam (CAZ-AVI) are limited. A systematic review and meta-analysis was conducted to clarify the role of CAZ-AVI for patients with serious Gram-negative bacterial infections. The PubMed, EMBASE and Cochrane Library databases were searched for randomised controlled trials (RCTs) and cohort studies involving CAZ-AVI. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. Twelve articles (4951 patients) were included, consisting of nine RCTs and three observational studies comparing CAZ-AVI with other regimens, e.g. carbapenems or colistin. CAZ-AVI showed a comparable clinical response (RR = 0.99, 95% CI 0.96-1.02; I2 = 0%) and non-inferior bacterial eradication (RR = 1.04, 95% CI 0.93-1.17; I2 = 79.1%) to carbapenems. No significant difference was detected between groups regarding mortality and adverse events. Moreover, subgroup analyses demonstrated that CAZ-AVI improved the clinical response (RR = 1.61, 95% CI 1.13-2.29) with reduced mortality (RR = 0.29, 95% CI 0.13-0.63) in patients infected by carbapenem-resistant Enterobacteriaceae versus comparators. Likewise, CAZ-AVI improved the clinical cure rate of bloodstream infections (RR = 2.11, 95% CI 1.54-2.88). An improved ability of CAZ-AVI in microbiological eradication was also detected in patients with complicated urinary tract infections (RR = 1.13, 95% CI 1.05-1.21). CAZ-AVI exhibited comparable efficacy and safety with carbapenems. Therefore, this agent might be a potential powerful agent for patients with serious Gram-negative bacterial infections.

Keywords: Avibactam; Carbapenem-resistant Enterobacteriaceae; Clinical response; Gram-negative bacteria; Microbiological response; Safety.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / therapeutic use*
  • Carbapenems / therapeutic use
  • Ceftazidime / therapeutic use*
  • Colistin / therapeutic use
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / physiology
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / mortality
  • Humans
  • Microbial Sensitivity Tests
  • Patient Safety
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Treatment Outcome
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / mortality

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Carbapenems
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime
  • Colistin