Comparative efficacy of ceftolozane–tazobactam versus ceftazidime–avibactam for Pseudomonas aeruginosa infections: a GRADE-assessed systematic review and meta-analysis

Background: Infections caused by multidrug-resistant/difficult-to-treat (MDR/DTR) Pseudomonas aeruginosa present a significant challenge for treatment. Ceftolozane–tazobactam (C/T) and ceftazidime–avibactam (C/A) are important options that combine β-lactam and β-lactamase inhibitors, but their effectiveness compared to each other is still unclear. Methods: We performed a systematic review and meta-analysis, evaluated by Grading of Recommendations Assessment, Development, and Evaluation (GRADE), of comparative observational studies that included hospitalized adults with confirmed MDR/DTR P. aeruginosa infections up to 10 October 2025 (English only). Studies comparing C/T directly with C/A and matched therapies were included. We used random-effects Mantel–Haenszel models to calculate pooled risk ratios (RR) with 95% confidence intervals (CIs), and we assessed heterogeneity with I 2 . We reviewed the certainty of evidence using GRADE. Results: Six observational cohorts ( n = 1161) met our criteria. There were no significant differences between C/T and C/A for clinical success (RR: 1.07, 0.89–1.29; I 2 = 40%), 30-day all-cause mortality (RR: 1.02, 95% CI: 0.83–1.27; I 2 = 0%), 30-day recurrence (RR: 0.85, 0.46–1.57; I 2 = 48%), 90-day recurrence (RR: 0.80, 0.63–1.02; I 2 = 0%; P = 0.08), emergence of resistance (RR: 0.73, 0.30–1.81; I 2 = 84%), and microbiological response failure (RR: 0.91, 0.66–1.26; I 2 = 8%). There was a non-significant trend that slightly favored C/T for 90-day recurrence. According to GRADE, the certainty of evidence varied from low to very low, mainly due to non-randomized study designs and variability across studies. Conclusions: In current comparative cohorts, C/T and C/A show similar outcomes for severe MDR/DTR P. aeruginosa infections. More high-quality randomized trials are needed to better define any potential differences and clarify long-term recurrence and resistance risks.