A systematic literature review and (network) meta-analysis of the effectiveness of ceftolozane/tazobactam versus aminoglycosides/polymyxins and ceftazidime/avibactam for treating adult patients with multidrug-resistant Pseudomonas aeruginosa infections.

Multidrug-resistantant (MDR) Pseudomonas aeruginosa is a major public health concern necessitating new antimicrobials. There are new antimicrobials available with activity against MDR-P. aeruginosa, but there is a lack of robust evidence synthesis to guide clinical decision-making for patients with infections caused by MDR-P. aeruginosa. This study, which was supported by Merck & Co., Inc., aimed to evaluate the real-world effectiveness of ceftolozane/tazobactam (C/T) compared to other commonly used therapies (aminoglycosides/polymyxins and ceftazidime/avibactam [CZA]) among adults with MDR-P. aeruginosa infections. A systematic literature review was conducted to identify real-world clinical and healthcare-resource utilization outcomes for C/T versus comparators. A feasibility assessment excluded comparators that were not aminoglycosides/polymyxins or CZA due to insufficient data for comparisons. A meta-analysis and network meta-analysis (NMA) were conducted on the included studies. Heterogeneity between the studies was calculated using I2 statistic. The NMA displayed statistically significant results for clinical cure (odds ratio [OR] = 0.308, 95% CI = 0.168-0.515) and all-cause mortality (OR = 1.651, 95% CI = 1.114-2.501) for C/T versus aminoglycosides/polymyxins, while microbiological cure and length of stay did not display statistical significance. However, comparisons for C/T versus CZA demonstrated no statistical significance for any of the outcomes explored. These findings suggest that C/T is more likely to achieve clinical cure and less likely to result in all-cause mortality compared to aminoglycosides/polymyxins. In the absence of head-to-head trials, this real-world evidence indicates potential advantages of using C/T over aminoglycosides/polymyxins for MDR-P. aeruginosa infections. Larger prospective studies with standardized outcome measures are needed to further inform clinical decision-making.