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

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.