RESTORE-IMI 1: A Multicenter, Randomized, Doubleblind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections

Motsch, Johann and Murta De Oliveira, Cláudia and Stus, Viktor and Köksal, Iftihar and Lyulko, Olexiy and Boucher, Helen W. and Kaye, Keith S. and File Jr, Thomas M. and Brown, Michelle L. and Khan, Ireen and Du, Jiejun and Joeng, Hee-Koung and Tipping, Robert W. and Aggrey, Angela and Young, Katherine and Kartsonis, Nicholas A. and Butterton, Joan R. and Paschke, Amanda (2020) RESTORE-IMI 1: A Multicenter, Randomized, Doubleblind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clinical Infectious Diseases, 70 (9). pp. 1799-1808. ISSN 1058-4838 (print), 1537-6591 (online)

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Abstract

Background. The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections. Methods. Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilatorassociated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenemnonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5–21 days imipenem/ relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment. Results. Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, –27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, –46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drugrelated deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively. Conclusions. Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections

Item Type:	Article
Additional Information:	https://doi.org/10.1093/cid/ciz530
Uncontrolled Keywords:	carbapenem resistant; KPC; nosocomial pneumonia; cIAI; cUTI.
Subjects:	Urology
Divisions:	Departments > Department of Urology
Depositing User:	Елена Шрамко
Date Deposited:	25 Nov 2019 12:46
Last Modified:	16 Sep 2020 13:42
URI:	http://repo.dma.dp.ua/id/eprint/4576

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