PMID- 31400759
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20220531
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 70
IP  - 9
DP  - 2020 Apr 15
TI  - 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.
PG  - 1799-1808
LID - 10.1093/cid/ciz530 [doi]
AB  - BACKGROUND: The beta-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/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. 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 drug-related 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. CLINICAL TRIALS REGISTRATION: NCT02452047.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Motsch, Johann
AU  - Motsch J
AD  - Universitatsklinikum Heidelberg, Germany.
FAU - Murta de Oliveira, Claudia
AU  - Murta de Oliveira C
AD  - Santa Casa de Misericordia, Belo Horizonte, Brazil.
FAU - Stus, Viktor
AU  - Stus V
AD  - Dnipropetrovsk Medical Academy, Dnipro, Ukraine.
FAU - Koksal, Iftihar
AU  - Koksal I
AD  - Karadeniz Technical University School of Medicine, Trabzon, Turkey.
FAU - Lyulko, Olexiy
AU  - Lyulko O
AD  - Department of Urology, Zaporozhye State Medical University, Zaporozhye, Ukraine.
FAU - Boucher, Helen W
AU  - Boucher HW
AD  - Tufts Medical Center, Boston, Massachusetts.
FAU - Kaye, Keith S
AU  - Kaye KS
AD  - University of Michigan, Ann Arbor, Michigan.
FAU - File, Thomas M
AU  - File TM
AD  - Summa Health, Akron, Ohio.
FAU - Brown, Michelle L
AU  - Brown ML
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Khan, Ireen
AU  - Khan I
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Du, Jiejun
AU  - Du J
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Joeng, Hee-Koung
AU  - Joeng HK
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Tipping, Robert W
AU  - Tipping RW
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Aggrey, Angela
AU  - Aggrey A
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Young, Katherine
AU  - Young K
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Kartsonis, Nicholas A
AU  - Kartsonis NA
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Butterton, Joan R
AU  - Butterton JR
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Paschke, Amanda
AU  - Paschke A
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT02452047
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Azabicyclo Compounds)
RN  - 71OTZ9ZE0A (Imipenem)
RN  - Y1MYA2UHFL (relebactam)
RN  - Z67X93HJG1 (Colistin)
SB  - IM
CIN - Clin Infect Dis. 2021 Apr 26;72(8):1485-1486. PMID: 32634242
CIN - Clin Infect Dis. 2021 Apr 26;72(8):1484-1485. PMID: 32634243
MH  - Anti-Bacterial Agents/adverse effects
MH  - Azabicyclo Compounds/adverse effects
MH  - *Bacterial Infections/drug therapy
MH  - Colistin/adverse effects
MH  - Humans
MH  - *Imipenem/adverse effects
MH  - Microbial Sensitivity Tests
PMC - PMC7156774
OTO - NOTNLM
OT  - KPC
OT  - cIAI
OT  - cUTI
OT  - carbapenem resistant
OT  - nosocomial pneumonia
EDAT- 2019/08/11 06:00
MHDA- 2021/01/07 06:00
PMCR- 2019/08/10
CRDT- 2019/08/11 06:00
PHST- 2019/03/05 00:00 [received]
PHST- 2019/06/24 00:00 [accepted]
PHST- 2019/08/11 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2019/08/11 06:00 [entrez]
PHST- 2019/08/10 00:00 [pmc-release]
AID - 5546004 [pii]
AID - ciz530 [pii]
AID - 10.1093/cid/ciz530 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2020 Apr 15;70(9):1799-1808. doi: 10.1093/cid/ciz530.