2406. “Real-world” Treatment of Multidrug-Resistant (MDR) or Extensively Drug-Resistant (XDR) P. aeruginosa Infections With Ceftolozane/Tazobactam (C/T) vs. a Polymyxin or Aminoglycoside (Poly/AG)-based Regimen: A Multicenter Comparative Effectiveness Study

BACKGROUND: The emergence of MDR/XDR P. aeruginosa has led to a reliance on suboptimal agents (Poly/AG) for the management of infections due to this pathogen. C/T is a novel agent with excellent in vitro activity against resistant P. aeruginosa that is indicated for cUTI and cIAI and being reviewed for VABP; however real-world comparative data for invasive infections are lacking. The purpose of this study was to assess comparative rates of clinical cure, mortality, and acute kidney injury (AKI) among patients treated with C/T vs. a Poly/AG based regimen for P. aeruginosa infections METHODS: This was a retrospective, multi-site cohort of adult inpatients from January 1, 2012 to February 28, 2018 with infections due to MDR or XDR P. aeruginosa. Patients treated for ≥48 hours with C/T or a Poly/AG-based regimen were eligible for inclusion. Patients with a creatinine clearance <20 mL/minute, or those requiring renal replacement therapy at baseline were excluded. Bivariate comparisons for baseline clinical characteristics and outcomes were assessed. RESULTS: A total of 117 (57 C/T, 60 Poly/AG) patients were included. Baseline characteristics, infection source, severity of illness, and time to appropriate therapy were similar between the treatment groups. Mean age was 58.6 ± 15.1 years, and 70% were male. Common comorbidities included diabetes (35%) and CHF (28%), and the median (IQR) Charlson Comorbidity Index was 3 (1–4). 42% of the population presented with severe sepsis or septic shock, and 68% were in the ICU at the onset of the infection. The most common infections were ventilator associated (54%) or hospital acquired (17%) pneumonia. Combination therapy was more frequently used in the Poly/AG group (72% vs. 12%; P < 0.001) Treatment with C/T was associated with a higher rate of clinical cure (79% vs. 62%; P = 0.046) and a lower incidence of AKI (7% vs. 33%; P < 0.001) compared with Poly/AG based therapy. In hospital mortality rates were similar (28% vs. 37%; P = 0.33). No patients receiving C/T had hypersensitivity reactions, neurological adverse events, or C. difficile infections. CONCLUSION: This multi-center retrospective analysis provides real-world data supporting improved outcomes with C/T compared with Poly/AG based regimens for invasive infections due to MDR/XDR P. aeruginosa. DISCLOSURES: J. M. Pogue, Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. Allergan: Speaker’s Bureau, Speaker honorarium. K. S. Kaye, Merck: Consultant and Grant Investigator, Consulting fee and Research grant. A. Ray, Merck: Speaker’s Bureau, Speaker honorarium. L. Puzniak, Merck: Employee, Salary. F. Perez, Merck: Grant Investigator, Grant recipient.