Pseudomonas aeruginosa infections that are MDR (multidrug-resistant), XDR (extensively drug-resistant), or DTR (difficult-to-treat) are becoming increasingly difficult to treat. Treatment of MDR and XDR Pseudomonas aeruginosa often involves the use of ceftolozane-tazobactam (C/T), a new β-lactam—β-lactamase inhibitor combination. Infections caused by MDR/XDR P. aeruginosa continue to originate most frequently in lower respiratory tract infections (LRTIs). To date, comparative effectiveness studies have been constrained by the use of specific comparator drugs (e.g., aminoglycosides and polymyxins) and the inclusion of a wide variety of infection sources (i.e., urinary tract, abdominal, skin, and soft tissue, etc.) From January 2014 through December 2019, researchers conducted a multicenter retrospective study of persons admitted with LRTI due to MDR or XDR P. aeruginosa. Their study’s primary objective was to evaluate and contrast the clinical outcomes of patients who were given C/T (n=118) with those of patients who were given the best available alternative treatment (n=88). Clinical failure, measured as either death within 30 days or a severe reaction to antibiotic treatment, was the primary endpoint. The study included 206 patients who met the criteria. The incidence of XDR P. aeruginosa and VAP was considerably greater in the C/T group ventilator-associated bacterial pneumonia (VABP). After controlling for confounding factors, multivariate logistic regression found that C/T treatment was independently related to a 73.3% reduction in clinical failure compared to those who received the best alternative therapy (P<0.001). There were just 3 times as many patients who needed harming with the best alternative therapy as there were with conventional treatment. Based on their findings, it appears that C/T is a viable therapy option for those with MDR and XDR Pseudomonas aeruginosa LRTI.