Real-World Applications of Imipenem-Cilastatin-Relebactam: Insights From a Multicenter Observational Cohort Study
Kaylee E Caniff, Nicholas Rebold, Xhilda Xhemali, Nikki Tran, Taryn A Eubank, Kevin W. Garey, Yi Guo, Mei H. Chang, Katie E. Barber, Tamara Krekel, Mark Biagi, Wesley D. Kufel, Amy Carr, Jillian E Hayes, Travis J Carlson, Jeremy J Frens, Veena Venugopalan, Kristen Lucas, Ashlan J. Kunz Coyne, James M. Sanders, Elisabeth Chandler, Rosanna Li, Kayla Antosz, Julie Ann Justo, Russell J Benefield, William J Moore, Jennifer Ross, Jenna C. Adams, Fritzie S Albarillo, Sylvia S. Stefanos, Athena L V Hobbs, Nicholas J. Mercuro, Brian R. Raux, Kristen Zeitler, Michael J. Rybak
Abstract
Abstract Background Multidrug-resistant (MDR) gram-negative infections are a substantial threat to patients and public health. Imipenem-cilastatin-relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor with expanded activity against MDR Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales. This study aims to describe the patient characteristics, prescribing patterns, and clinical outcomes associated with IMI/REL. Methods This was a retrospective, multicenter, observational study of patients ≥18 years old who received IMI/REL for ≥48 hours for a suspected or confirmed gram-negative infection. The primary outcome was clinical success, defined as improvement or resolution of infection-related signs or symptoms while receiving IMI/REL and the absence of 30-day microbiologic failure. Multivariable logistic regression analysis was performed to identify independent predictors of clinical success. Results The study included 151 patients from 24 US medical centers. IMI/REL was predominantly prescribed for lower respiratory tract infections, accounting for 52.3% of cases. Most patients were infected with a carbapenem-nonsusceptible pathogen (85.4%); P aeruginosa was frequently targeted (72.2%). Clinical success was achieved in 70.2% of patients. Heart failure, receipt of antibiotics within the past 90 days, intensive care unit admission at time of index culture collection, and isolation of difficult-to-treat resistant P aeruginosa were independently associated with a reduced odds of clinical success. Adverse events were reported in 6.0% of patients, leading to discontinuation of IMI/REL in 3 instances. Conclusions This study provides a comprehensive analysis of the real-world effectiveness and safety of IMI/REL. Comparative studies and investigations of specific subgroups will further enhance our understanding of IMI/REL in treating MDR infections.