MIRAGE
Effectiveness of iMIpenem-Relebactam for multidrug-resistant Pseudomonas AeruGinosa in pnEumonia and bloodstream infections in the United States
Background
Imipenem-relebactam is recommended as a preferred treatment option for multidrug resistant and difficult-to-treat P. aeruginosa infections by IDSA1,2. The agent demonstrates potent in vitro activity against MDR P. aeruginosa, optimized PK-PD,3 and encouraging efficacy in clinical trials4,5.
In the challenging setting of resistance to C/T, imipenem-relebactam retains potent in vitro activity.6 Real-world evidence, however, is extremely limited,7,8 and few patients enrolled in a randomized clinical trial of HAP/VAP were infected with MDR P. aeruginosa5. Clinical use in the U.S. has generally been restricted to salvage situations8. ESCMID guidelines have concluded that there is insufficient evidence to recommend imipenem-relebactam until further data are available.
Details
MIRAGE is a retrospective, multicenter, observational study describing the clinical effectiveness of imipenem-relebactam against multidrug-resistant P. aeruginosa pneumonia and bloodstream infections in real-world settings.
Clinical efficacy, treatment response, and emergence of resistance will all be studied. Available isolates will be collected from participating sites for molecular characterization, identification of resistance mechanisms, and standardized susceptibility testing for imipenem-relebactam by broth microdilution.
Progress
Stay tuned for announcements of preliminary data reports.
References:
1. O'Donnell JN, Lodise TP. New Perspectives on Antimicrobial Agents: Imipenem-Relebactam. Antimicrob Agents Chemother 2022;66(7):e0025622. DOI: 10.1128/aac.00256-22.
2. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum beta-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis 2020. DOI: 10.1093/cid/ciaa1478.
3. Rizk ML, Rhee EG, Jumes PA, et al. Intrapulmonary Pharmacokinetics of Relebactam, a Novel beta-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects. Antimicrobial agents and chemotherapy 2018;62(3). DOI: 10.1128/AAC.01411-17.
4. Titov I, Wunderink RG, Roquilly A, et al. A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study). Clin Infect Dis 2020. DOI: 10.1093/cid/ciaa803.
5. Motsch J, Murta de Oliveira C, Stus V, et al. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis 2019. DOI: 10.1093/cid/ciz530.
6. Rubio AM, Kline EG, Jones CE, et al. In Vitro Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa following Treatment-Emergent Resistance to Ceftolozane-Tazobactam. Antimicrob Agents Chemother 2021;65(6). DOI: 10.1128/AAC.00084-21.
7. Rebold N, Morrisette T, Lagnf AM, et al. Early Multicenter Experience With Imipenem-Cilastatin-Relebactam for Multidrug-Resistant Gram-Negative Infections. Open Forum Infect Dis 2021;8(12):ofab554. DOI: 10.1093/ofid/ofab554.
8. Shields RK, Stellfox ME, Kline EG, Samanta P, Van Tyne D. Evolution of Imipenem-Relebactam Resistance Following Treatment of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia. Clin Infect Dis 2022;75(4):710-714. DOI: 10.1093/cid/ciac097.