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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

The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquir...

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Main Authors: Motsch, Johann (Author) , Murta de Oliveira, Cláudia (Author) , Stus, Viktor (Author) , Köksal, Iftihar (Author) , Lyulko, Olexiy (Author) , Boucher, Helen W (Author) , Kaye, Keith S (Author) , File, Thomas M, Jr (Author) , Brown, Michelle L (Author) , Khan, Ireen (Author) , Du, Jiejun (Author) , Joeng, Hee-Koung (Author) , Tipping, Robert W (Author) , Aggrey, Angela (Author) , Young, Katherine (Author) , Kartsonis, Nicholas A (Author) , Butterton, Joan R (Author) , Paschke, Amanda (Author)
Format: Article (Journal)
Language:English
Published: 2020
In: Clinical infectious diseases
Year: 2019, Volume: 70, Issue: 9, Pages: 1799-1808
ISSN:1537-6591
DOI:10.1093/cid/ciz530
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/cid/ciz530
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/cid/article/70/9/1799/5546004
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Author Notes:Johann Motsch, Cláudia Murta de Oliveira, Viktor Stus, Iftihar Köksal, Olexiy Lyulko, Helen W. Boucher, Keith S. Kaye, Thomas M. File Jr, Michelle L. Brown, Ireen Khan, Jiejun Du, Hee-Koung Joeng, Robert W. Tipping, Angela Aggrey, Katherine Young, Nicholas A. Kartsonis, Joan R. Butterton, and Amanda Paschke
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Summary:The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (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.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 drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively.Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections.NCT02452047.
Item Description:Published online August 10, 2019
Gesehen am 31.03.2021
Physical Description:Online Resource
ISSN:1537-6591
DOI:10.1093/cid/ciz530

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