Imipenem/cilastatin/relebactam treatment of hospital-acquired/ventilator-associated bacterial pneumonia caused by imipenem-nonsusceptible pathogens: Subgroup analysis and molecular characterization of isolates from the RESTORE-IMI 2 clinical study
- 1Merck & Co., Inc., Rahway, New Jersey, United States of America
Abstract
Background: Additional treatment options are needed for patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by carbapenem-resistant pathogens. This subgroup analysis examined clinical and microbiologic outcomes in participants from RESTORE-IMI 2 treated with imipenem/cilastatin/relebactam (IMI/REL), stratified by baseline lower respiratory tract (LRT) isolate susceptibility to imipenem. Emergence of nonsusceptibility to IMI/REL during treatment was also evaluated. Methods: Baseline LRT specimens were obtained ≤48 hours before screening, identified at a central laboratory, and susceptibility determined per the Clinical and Laboratory Standards Institute breakpoints. Outcomes for participants who received IMI/REL, with ≥1 imipenem-nonsusceptible, imipenem/REL-susceptible baseline LRT pathogen were compared with participants with imipenem-susceptible pathogens. Emergence of nonsusceptibility to imipenem/REL was also assessed, and isolates were characterized molecularly. Results: In total, 215 participants in the microbiologic-modified intent-to-treat population received IMI/REL, of whom 112 were infected with imipenem-susceptible pathogens and 18 with imipenem-nonsusceptible, imipenem/REL-susceptible pathogens and were included in this analysis. Of these 18 participants, 88.9% were in the intensive care unit and 83.3% had one gram-negative baseline pathogen. Day 28 all-cause mortality was 22.2% and 18.8% (adjusted difference: 7.3 [−8.8 to 31.1]) for participants who received IMI/REL for the treatment of HABP/VABP caused by imipenem-nonsusceptible versus imipenem-susceptible pathogens, respectively. Of a total of 192 isolates, 59 gram-negative isolates (baseline isolates that were nonsusceptible to imipenem and subsequent isolates of the same species from the same participants) were characterized using multiplex polymerase chain reaction and sequencing techniques. Emergence of nonsusceptibility to imipenem/REL occurred in isolates from three of the 112 participants with indicated imipenem-susceptible baseline pathogens (two isolates of Pseudomonas aeruginosa and one isolate of Klebsiella pneumoniae). Conclusions: Day 28 all-cause mortality was similar among participants treated with IMI/REL, regardless of baseline pathogen susceptibility to imipenem. Emergence of nonsusceptibility to imipenem/REL on treatment was low. Clinical trials registration: ClinicalTrials.gov (NCT02493764).
Related
- Cilastatin Protects Against Chemotherapy-Induced Neuropathy via the FKBP51/DPEP1 Axis: Confocal Insights into Protein Dynamics
- Diverse transcriptomic effects of evolved imipenem-relebactam resistance in Pseudomonas aeruginosa
- DONSON-Associated MISSLA with Co-Occurring p.Arg442Ter and p.Lys489Thr Variants: Longitudinal Clinical and Genomic Characterization
- Morphological, molecular, and pathogenic characterization of five Fusarium species associated with coffee berry rot in Malaysia
- Screening and characterization of endophytic bacterial isolates associated with Echinops kebericho M. and Lepidium sativum L. and evaluation of their potential role
BibTeX
@article{young2026imipenemcilastatinrelebactam,
title = {{Imipenem/cilastatin/relebactam treatment of hospital-acquired/ventilator-associated bacterial pneumonia caused by imipenem-nonsusceptible pathogens: Subgroup analysis and molecular characterization of isolates from the RESTORE-IMI 2 clinical study}},
author = {Katherine Young and C. Andrew DeRyke and David W. Hilbert and Maria C. Losada and Jiejun Du and Amanda Paschke and Luke F. Chen},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357288},
url = {https://doi.org/10.1371/journal.pone.0357288},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Imipenem/cilastatin/relebactam treatment of hospital-acquired/ventilator-associated bacterial pneumonia caused by imipenem-nonsusceptible pathogens: Subgroup analysis and molecular characterization of isolates from the RESTORE-IMI 2 clinical study
AU - Katherine Young
AU - C. Andrew DeRyke
AU - David W. Hilbert
AU - Maria C. Losada
AU - Jiejun Du
AU - Amanda Paschke
AU - Luke F. Chen
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0357288
UR - https://doi.org/10.1371/journal.pone.0357288
AB - Background: Additional treatment options are needed for patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by carbapenem-resistant pathogens. This subgroup analysis examined clinical and microbiologic outcomes in participants from RESTORE-IMI 2 treated with imipenem/cilastatin/relebactam (IMI/REL), stratified by baseline lower respiratory tract (LRT) isolate susceptibility to imipenem. Emergence of nonsusceptibility to IMI/REL during treatment was also evaluated. Methods: Baseline LRT specimens were obtained ≤48 hours before screening, identified at a central laboratory, and susceptibility determined per the Clinical and Laboratory Standards Institute breakpoints. Outcomes for participants who received IMI/REL, with ≥1 imipenem-nonsusceptible, imipenem/REL-susceptible baseline LRT pathogen were compared with participants with imipenem-susceptible pathogens. Emergence of nonsusceptibility to imipenem/REL was also assessed, and isolates were characterized molecularly. Results: In total, 215 participants in the microbiologic-modified intent-to-treat population received IMI/REL, of whom 112 were infected with imipenem-susceptible pathogens and 18 with imipenem-nonsusceptible, imipenem/REL-susceptible pathogens and were included in this analysis. Of these 18 participants, 88.9% were in the intensive care unit and 83.3% had one gram-negative baseline pathogen. Day 28 all-cause mortality was 22.2% and 18.8% (adjusted difference: 7.3 [−8.8 to 31.1]) for participants who received IMI/REL for the treatment of HABP/VABP caused by imipenem-nonsusceptible versus imipenem-susceptible pathogens, respectively. Of a total of 192 isolates, 59 gram-negative isolates (baseline isolates that were nonsusceptible to imipenem and subsequent isolates of the same species from the same participants) were characterized using multiplex polymerase chain reaction and sequencing techniques. Emergence of nonsusceptibility to imipenem/REL occurred in isolates from three of the 112 participants with indicated imipenem-susceptible baseline pathogens (two isolates of Pseudomonas aeruginosa and one isolate of Klebsiella pneumoniae). Conclusions: Day 28 all-cause mortality was similar among participants treated with IMI/REL, regardless of baseline pathogen susceptibility to imipenem. Emergence of nonsusceptibility to imipenem/REL on treatment was low. Clinical trials registration: ClinicalTrials.gov (NCT02493764).
SN - 1932-6203
ER -