Introduction

Carbapenem-resistant Enterobacteriaceae (CRE) is increasingly recognised as a significant public health concern. Recently, polymyxins were reintroduced into medical practice as one of the last resorts for treating extensively drug-resistant gram-negative bacteria. Also, a meta-analysis demonstrated that ceftazidime-avibactam (CAZ-AVI) might be an option for empirical therapy of CRE infection.

Aim

To conduct a meta-analysis to compare the clinical efficacy and safety of CAZ-AVI relative to polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections.

Patient Profile

• 1111 patients with carbapenem-resistant Enterobacteriaceae infections

  Method

  Study Design

  Endpoints

  Results

  Efficacy

• CAZ-AVI treatment groups demonstrated a significantly lower 30-day mortality compared with polymyxins groups (risk ratio, RR 0.48, I²=10%, p<0.0001) in nine studies (n=766) in patients with carbapenem-resistant Enterobacteriaceae infections

• Systematic review and meta-analysis of seven retrospective and four prospective cohort studies
• Eligible studies included all available published studies that compared CAZ-AVI with polymyxins for the treatment of CRE infections in adult patients (>18 years)
• CAZ-AVI or polymyxins-based combined administration schemes were included

• Mortality, clinical success, microbiological eradication and nephrotoxicity

• CAZ-AVI treatment groups showed higher clinical success versus polymyxins groups (RR 1.71, I²=35%, p<0.0001) in four studies (n=463)
• No significant difference was observed in microbiological eradication rates with CAZ-AVI or polymyxins (RR 1.16, I²=0, p>0.05) in two studies (n=249;)
• All included studies had low risk of bias (Newcastle–Ottawa Scale scores ≥7 [graded as high quality])

Figure 1: Effect of ceftazidime-avibactam and polymyxins on outcomes

Safety 

• Lower nephrotoxicity was seen in CAZ-AVI treatment groups compared with polymyxins (RR 0.42, I²=35%, p<0.05) in seven studies (n=696)

  Conclusion

• CAZ-AVI treatment was superior with respect to efficacy and safety compared with polymyxins in carbapenem-resistant Enterobacteriaceae infections
• This is the first of its kind meta-analysis to compare the efficacy and safety of CAZ-AVI with polymyxins in treating CRE infection

BMJ Open 2023; 13(5): e070491