The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of People With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens
Issued Date
2026-03-15
Resource Type
ISSN
10584838
eISSN
15376591
Scopus ID
2-s2.0-105032305988
Pubmed ID
40682801
Journal Title
Clinical Infectious Diseases
Volume
82
Issue
3
Start Page
391
End Page
398
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Infectious Diseases Vol.82 No.3 (2026) , 391-398
Suggested Citation
Huralska M., Pogue J.M., Rybak M., Abdul-Mutakabbir J.C., Stamper K., Marchaim D., Thamlikitkul V., Carmeli Y., Chiu C.H., Daikos G., Dhar S., Durante-Mangoni E., Gikas A., Kotanidou A., Paul M., Roilides E., Samarkos M., Sims M., Tancheva D., Tsiodras S., Kett D.H., Patel G., Calfee D.P., Leibovici L., Power L., Munoz-Price S., Shaikh H., Susick L., Latack K., Chiou C., Divine G., Ghazyaran V., Kaye K.S. The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of People With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens. Clinical Infectious Diseases Vol.82 No.3 (2026) , 391-398. 398. doi:10.1093/cid/ciaf398 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115895
Title
The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of People With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens
Author(s)
Huralska M.
Pogue J.M.
Rybak M.
Abdul-Mutakabbir J.C.
Stamper K.
Marchaim D.
Thamlikitkul V.
Carmeli Y.
Chiu C.H.
Daikos G.
Dhar S.
Durante-Mangoni E.
Gikas A.
Kotanidou A.
Paul M.
Roilides E.
Samarkos M.
Sims M.
Tancheva D.
Tsiodras S.
Kett D.H.
Patel G.
Calfee D.P.
Leibovici L.
Power L.
Munoz-Price S.
Shaikh H.
Susick L.
Latack K.
Chiou C.
Divine G.
Ghazyaran V.
Kaye K.S.
Pogue J.M.
Rybak M.
Abdul-Mutakabbir J.C.
Stamper K.
Marchaim D.
Thamlikitkul V.
Carmeli Y.
Chiu C.H.
Daikos G.
Dhar S.
Durante-Mangoni E.
Gikas A.
Kotanidou A.
Paul M.
Roilides E.
Samarkos M.
Sims M.
Tancheva D.
Tsiodras S.
Kett D.H.
Patel G.
Calfee D.P.
Leibovici L.
Power L.
Munoz-Price S.
Shaikh H.
Susick L.
Latack K.
Chiou C.
Divine G.
Ghazyaran V.
Kaye K.S.
Author's Affiliation
University of Michigan, Ann Arbor
Weill Cornell Medicine
National and Kapodistrian University of Athens
Wayne State University
Wayne State University School of Medicine
Università degli Studi della Campania Luigi Vanvitelli
National Institute of Allergy and Infectious Diseases (NIAID)
School of Medicine
Robert Wood Johnson Medical School
Chang Gung University College of Medicine
Tel Aviv Sourasky Medical Center
Rabin Medical Center Israel
Siriraj Hospital
The Mount Sinai Hospital
Attikon University Hospital
Henry Ford Health System
Shamir Medical Center
Heraklion University Hospital
Skaggs School of Pharmacy & Pharmaceutical Sciences
Faculty of Health Sciences
UHealth Tower
Emergency Hospital Pirogov
Infectious Diseases Institute
Emerald Coast Infectious Diseases
Corewell Health William Beaumont University Hospital
Weill Cornell Medicine
National and Kapodistrian University of Athens
Wayne State University
Wayne State University School of Medicine
Università degli Studi della Campania Luigi Vanvitelli
National Institute of Allergy and Infectious Diseases (NIAID)
School of Medicine
Robert Wood Johnson Medical School
Chang Gung University College of Medicine
Tel Aviv Sourasky Medical Center
Rabin Medical Center Israel
Siriraj Hospital
The Mount Sinai Hospital
Attikon University Hospital
Henry Ford Health System
Shamir Medical Center
Heraklion University Hospital
Skaggs School of Pharmacy & Pharmaceutical Sciences
Faculty of Health Sciences
UHealth Tower
Emergency Hospital Pirogov
Infectious Diseases Institute
Emerald Coast Infectious Diseases
Corewell Health William Beaumont University Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
Background. Colistin, a last-line treatment for carbapenem-resistant Gram-negative bacilli (CRGNB), is frequently used in combination with meropenem because these agents often demonstrate in vitro synergy. Using data from the OVERCOME trial comparing colistin + meropenem to colistin + placebo for treatment of pneumonia or bloodstream infection due to CRGNB, we evaluated the impact of synergistic therapy on outcomes. Methods. In vitro synergy testing between colistin and meropenem was conducted using 24-hour time-kill analysis; synergy was defined as >2-log reduction in colony-forming units/mL compared to the most active single agent. Patients receiving synergistic combination therapy were compared to patients receiving functional colistin monotherapy (colistin alone or combination therapy without synergy). Outcomes included mortality, clinical failure, and microbiologic cure. Adjusted analyses controlled for variables on which randomization was stratified and confounders. Results. A total of 146 subjects receiving synergistic combination therapy and 261 subjects receiving functional monotherapy were included. Most had pneumonia (70%), CR Acinetobacter baumannii infection (79%) and were in intensive care (69%). Acinetobacter baumannii was more common in those receiving synergistic combination therapy than functional monotherapy (P <.001). Mortality rates were similar (38.3% and 41.4%, respectively). In adjusted analyses, synergistic combination therapy was associated with significantly lower clinical failure rates (55.3%, 64.3%, adjusted odds ratio [aOR] 0.62, P =.049), with consistent findings in pneumonia (62.6%, 71.8%, aOR 0.55, P =.04) and A. baumannii subgroups (57.4%, 69.4%, aOR 0.60, P =.06). Microbiologic cure rates were similar. Conclusions. Colistin-based, synergistic combination treatment with meropenem (compared to nonsynergistic colistin-based therapy) was associated with decreased clinical failure, particularly in people with pneumonia and A. baumannii.