Efficacy and Safety of Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Enterobacterales Bloodstream Infection: a Systematic Review and Meta-Analysis

Several clinicians use ceftazidime-avibactam (CAZ-AVI) to treat bloodstream infections (BSIs) due to carbapenem-resistant Enterobacterales (CRE), although no conclusive data support this practice. We aimed to assess the efficacy and safety of CAZ-AVI in the treatment of CRE bacteremia. PubMed, Embase, and Cochrane Library were systematically searched until 5 November 2021. Studies comparing the clinical outcome of CAZ-AVI with other regimens in CRE BSI were included if they reported data on mortality. Results were expressed as risk ratios (RRs) or mean differences with accompanying 95% confidence intervals (95% CIs). Eleven articles with 1,205 patients were included. CAZ-AVI groups showed a significantly lower 30-day mortality than control groups of other regimens (RR = 0.55, 95% CI of 0.45 to 0.68, P < 0.00001). The result is robust when a colistin-based regimen serves as the control group (RR = 0.48, 95% CI 0.33 of 0.69, P < 0.0001). In subgroup meta-analyses, the 30-day mortality was significantly lower in patients infected with CRE producing Klebsiella pneumoniae carbapenemase (RR = 0.59, 95% CI of 0.46 to 0.75, P < 0.0001). Additionally, patients in CAZ-AVI groups had a significantly higher clinical cure rate (RR = 1.75, 95% CI of 1.57 to 2.18, P < 0.00001) and lower nephrotoxicity rate (RR = 0.41, 95% CI of 0.20 to 0.84, P = 0.02). No significant differences of relapse rates were demonstrated in 2 groups (RR = 0.69, 95% CI of 0.29 to 1.66, P = 0.41). Although the current study is based on observational studies with a small sample of participants, the findings suggest that CAZ-AVI treatment is effective and safe compared with other antibiotics, including colistin, in CRE BSI. IMPORTANCE Ceftazidime-avibactam (CAZ-AVI) has been used as a frontline agent in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, the efficacy and safety of CAZ-AVI on carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) remain unclear. Patients with CRE BSIs were often enrolled in small-sized clinical studies, together with other sites of infections, which reported pooled results. In this meta-analysis, the efficacy and safety were compared between CAZ-AVI and any other regimens used against CRE infections. The findings suggest that patients in the CAZ-AVI group had a significantly lower 30-day mortality than any other regimens and than colistin-based regimens. This paper provides a rationale for the use of CAZ-AVI in one of the most urgent antimicrobial-resistant infections of CRE bloodstream infections.