Real-World Antibiotic Strategies for Multidrug-Resistant Pseudomonas aeruginosa: Evidence from the Italian SUSANA Multicentre Study

Background/Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa pneumonia and bloodstream infections (BSI) remain challenging because of their severity, limited therapeutic options, and high mortality, despite the availability of novel β-lactam-based agents. We aimed to describe real-world treatment patterns, characteristics associated with treatment and infusion-strategy selection, and the association of these strategies with clinical outcomes in the retrospective, multicentre Italian SUSANA cohort, an observational study evaluating the use, safety, and outcomes of novel antibiotics in hospitalized patients. Methods: Adults with MDR P. aeruginosa pneumonia and/or BSI treated with novel antipseudomonal agents for ≥72 h were included. Treatment was classified as monotherapy or combination therapy, and infusion strategy as prolonged/continuous or standard. The primary outcome was 28-day all-cause mortality. A multivariable Cox regression analysis was performed. Results: Among 173 patients, pneumonia was the most frequent clinical presentation (74.0%). Monotherapy was used in 111 patients (64.2%), combination therapy in 62 (35.8%), and prolonged/continuous infusion in 120 (69.4%). Ceftolozane–tazobactam (CT) (64.7%) and ceftazidime–avibactam (CZA) (20.2%) were the most prescribed agents. Patients receiving prolonged/continuous infusion, regardless of monotherapy or combination therapy, had greater baseline clinical severity than those receiving standard infusion. Overall, 28-day mortality was 23.7%. In the multivariable analysis, neither combination therapy nor prolonged/continuous infusion was independently associated with reduced mortality, whereas septic shock (aHR 4.10, 95% CI 1.01–16.66) and ICU admission (aHR 2.53, 95% CI 1.06–6.08) increased mortality risk. Conclusions: In this multicentre real-world cohort, treatment strategies for MDR P. aeruginosa pneumonia and BSI appeared to be influenced by baseline severity and patient-related factors. Mortality was more strongly associated with markers of severe illness, including ICU admission and septic shock. No independent association with improved survival was observed for combination therapy compared with monotherapy or for prolonged/continuous compared with standard infusion. These findings highlight the prognostic role of baseline clinical severity and support the need for prospective, randomized, pharmacokinetic/pharmacodynamic (PK/PD)-guided studies to identify patients who may benefit from these strategies.