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 of multidrug-resistant (MDR) and/or difficult-to-treat (DTR) Pseudomonas aeruginosa (PA) infections. Conflicting results in terms of clinical outcome and resistance development emerged from real-world comparative studies. We perform a systematic review with meta-analysis for comparing ceftolozane-tazobactam and ceftazidime-avibactam in the treatment of MDR/DTR PA infections. Methods: Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 18th November 2025 for retrieving studies comparing ceftolozane-tazobactam vs. ceftazidime-avibactam in the management of MDR/DTR-PA infections. Clinical cure was set as the primary outcome, whereas 90-day resistance development, microbiological failure, and 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. Risk of bias of the included studies was independently assessed according to the RoB 2.0 and the ROBINS-I tools. Results: Among a total of 1,193 articles screened, six observational studies were retrieved and included (N=1,161, 644 receiving ceftolozane-tazobactam vs. 517 receiving ceftazidime-avibactam). Ceftolozane-tazobactam showed higher clinical cure rate compared to ceftazidime-avibactam (N=4; OR 1.82; 95%CI 1.10-2.99; I2=25.3%). No difference emerged in terms of microbiological failure (N=2; OR 0.66; 95%CI 0.36-1.19; I2=21.9%), 90-day resistance development (N=3; OR 1.11; 95%CI 0.51-2.42; I2=50.0%) and 30-day mortality rate (N=4; OR 1.00; 95%CI 0.89-1.12; I2=0.0%). Conclusions: Our meta-analysis showed that, after adjusting appropriately for confounders, ceftolozane-tazobactam could grant higher clinical cure rate in the treatment of MDR/DTR PA infections compared to ceftazidime-avibactam.