Comparison of ceftolozane–tazobactam and ceftazidime–avibactam for the treatment of infections caused by drug-resistant Pseudomonas aeruginosa: An updated systematic review and meta-analysis based on adjusted data from observational studies

BACKGROUND: Clinical guidelines recommend two novel β-lactam/β-lactamase inhibitor combinations-ceftolozane-tazobactam and ceftazidime-avibactam-as first-line therapies for drug-resistant Pseudomonas aeruginosa infections. This study aimed to compare their efficacy, safety, and emergence of resistance. METHODS: A systematic review and meta-analysis was conducted. The primary analysis was based on adjusted data from direct comparisons. To assess robustness, these findings were compared with pooled estimates from unadjusted direct and indirect comparisons. Outcomes included all-cause mortality, clinical response, pathogen clearance, recurrent infection, AKI, and in vivo emergence of resistance. Risk of bias was assessed using the ROBINS-I tool based on prespecified confounders. RESULTS: Twenty-two studies including 3,361 patients were analyzed. No significant differences were observed between the two agents in all-cause mortality, clinical response, AKI, and emergence of resistance. However, ceftolozane-tazobactam was associated with a lower risk of recurrent infection within 30-90 days compared with ceftazidime-avibactam (aOR = 0.46, 95% CI 0.26-0.78). CONCLUSION: Ceftolozane-tazobactam and ceftazidime-avibactam demonstrate comparable efficacy and similar risks of resistance emergence. Moderate-certainty evidence suggests that ceftolozane-tazobactam may reduce the risk of recurrent infection in patients with drug-resistant P. aeruginosa infections.