Comparison of early treatment with ceftolozane/tazobactam versus polymyxin-based therapy of pneumonia due to MDR <i>Pseudomonas</i> <i>aeruginosa</i> (PUMA)

Ceftolozane/tazobactam and polymyxin-based regimens are frequently used to treat pneumonia caused by multi-drug-resistant <i>P. aeruginosa</i> (MDR-PSA). However, comparative data on global clinical outcomes between these therapies are limited. A multi-centered observational study was performed using the PINC AI^TM Healthcare Database (2016-2022). The study population included hospitalized patients ≥ 18 years who were diagnosed with pneumonia and had MDR-PSA (defined as non-susceptible to ≥1 agent in ≥3 antimicrobial categories) on a respiratory or blood culture, receipt of ceftolozane/tazobactam or a polymyxin-based regimen within 3 days of index MDR-PSA culture, receipt of ≥2 days of ceftolozane/tazobactam or a polymyxin-based regimen, and without a COVID-19 diagnosis. A Desirability of Outcome Ranking (DOOR) analysis was performed. Components of the DOOR included in-hospital mortality, discharge destination (home vs other), recurrent MDR-PSA pneumonia, receipt of any renal replacement therapy (RRT) post-index culture in RRT-naive patients, and 30-day pneumonia-related readmissions. In total, 186 patients met the study criteria (104 ceftolozane/tazobactam and 82 polymyxin). In the IPW-adjusted DOOR analysis, a ceftolozane/tazobactam-treated patient had a higher probability of a more favorable outcome (DOOR probability: 61.3%; 95% CI: 56.8%, 65.7%). In the DOOR partial credit analyses, a ceftolozane/tazobactam-treated patient had a higher probability of being discharged home alive with no undesirable outcomes than a polymyxin-treated patient (20.2% vs 9.8%, <i>P</i> = 0.04). This real-world evidence study of non-COVID-19 patients with MDR-PSA pneumonia suggests that patients treated with ceftolozane/tazobactam have a higher probability of a more favorable outcome compared with patients treated with a polymyxin-based regimen. Further large-scale studies with detailed dosing are needed to validate the findings.