Comparison of Ceftolozane-Tazobactam and Ceftazidime-Avibactam in the Treatment of Multidrug-Resistant/Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-analysis

BACKGROUND: Ceftolozane-tazobactam and ceftazidime-avibactam are considered first-line treatment for multidrug-resistant (MDR) and/or difficult-to-treat resistant (DTR) Pseudomonas aeruginosa infections. Conflicting results in terms of clinical outcome and resistance development emerged from real-world comparative studies. We performed a systematic review with meta-analysis to compare ceftolozane-tazobactam and ceftazidime-avibactam in the treatment of MDR/DTR P. aeruginosa infections. METHODS: Two authors independently searched PubMed-MEDLINE and Scopus databases from inception to 18 November 2025 to retrieve studies comparing ceftolozane-tazobactam versus ceftazidime-avibactam in the management of MDR/DTR P. aeruginosa infections. Clinical cure was set as the primary outcome, whereas 90-day resistance development, microbiological failure, and the 30-day mortality rate were set as the secondary outcomes. Meta-analysis was performed by pooling the odds ratios (ORs) retrieved from studies providing adjustment for confounders by means of a random-effects model with the inverse variance method. The risk of bias in the included studies was independently assessed using the RoB 2.0 and the ROBINS-I tools. RESULTS: Among a total of 1193 articles screened, 6 observational studies were retrieved and included (n = 1161; 644 receiving ceftolozane-tazobactam vs 517 receiving ceftazidime-avibactam). Ceftolozane-tazobactam showed a higher clinical cure rate than ceftazidime-avibactam (n = 4; OR, 1.82 [95% confidence interval, 1.10-2.99]; I2 = 25.3%). No difference emerged in terms of microbiological failure (n = 2; OR, 0.66 [95% confidence interval, .36-1.19]; I2 = 21.9%), 90-day resistance development (n = 3; OR, 1.11 [.51-2.42]; I2 = 50.0%), or 30-day mortality rate (n = 4; OR, 1.00 [.89-1.12]; I2 = 0.0%). CONCLUSIONS: Our meta-analysis showed that, after appropriate adjustment for confounders, ceftolozane-tazobactam could grant a higher clinical cure rate than ceftazidime-avibactam in the treatment of MDR/DTR P. aeruginosa infections.