Abstract
BACKGROUND: Imipenem/relebactam (I/R) demonstrates potent in vitro activity against multidrug-resistant (MDR) Pseudomonas aeruginosa. The objective of this study was to evaluate the effectiveness of I/R for treatment of MDR P. aeruginosa infections across the U.S. [Figure: see text] [Figure: see text] METHODS: This was a retrospective, multicenter, observational study of I/R for MDR P. aeruginosa pneumonia and bacteremia. Patients were included if they received I/R for >48h initiated within 7 days of the index MDR P. aeruginosa culture (Table 1). Clinical success was defined as survival, resolution of signs and symptoms of infection, completion of the intended treatment course, and the absence of a recurrent infection due to MDR P. aeruginosa. I/R susceptibility was determined by site-level microbiology labs; non-susceptibility was defined by the Clinical and Laboratory Standards Institute (CLSI) criteria. [Figure: see text] [Figure: see text] RESULTS: 64 patients from 10 centers were included (Table 2); patients from 6 additional centers were screened and did not meet inclusion criteria. The overall cohort was critically-ill; 80%, 75%, and 48% were in the intensive care unit, receiving mechanical ventilation, and on vasopressors, respectively. The median (interquartile range; IQR) SOFA score was 7 (5 – 12). 53% received treatment with another new β-lactam for MDR P. aeruginosa infections prior to I/R. The median time to I/R initiation was 67 hours. I/R treatment was primarily prescribed based on susceptibility results in 75% of patients, including resistance to other novel β-lactam agents (Table 3). 63% of patients completed the intended I/R treatment course as planned. At day 7 and 30, 80% and 55% met criteria for clinical success, respectively (Table 4). The overall 30- and 90-day mortality rates were 17% and 30%, respectively. Recurrent infections were documented in 38% of patients within 90 days. CONCLUSION: In this critically-ill patient population we found that I/R was often used following treatment with other novel β-lactams. Clinical outcomes were generally comparable to those previously reported in similar real-world studies for other novel β-lactam agents suggesting that I/R plays a role in treatment of MDR P. aeruginosa infections, particularly when other agents are not available or test resistant. DISCLOSURES: jason M. Pogue, PharmD, Entasis: Advisor/Consultant|Entasis: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support Alexander J. Lepak, MD, FIDSA, BioMerieux: Grant/Research Support William R. Miller, M.D., Merck: Grant/Research Support|UpToDate: Royalties, topic author Jeffrey C. Pearson, PharmD, InflaRx Pharmaceuticals, Inc.: Advisor/Consultant Emre Yucel, PhD, Merck & Co., Ltd: Stocks/Bonds (Public Company)