Evidence map›Paper›PMID 40682801›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2026

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.

Mariya Huralska, Jason M Pogue, Michael Rybak, Jacinda C Abdul-Mutakabbir, Kyle Stamper, Dror Marchaim, Visanu Thamlikitkul, Yehuda Carmeli, Cheng-Hsun Chiu, George Daikos and 23 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Challenges and opportunities in the management of severe pneumonia. Key concepts from the Seventh Annual Meeting of Spanish Experts 2025.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026
    Review
  4. Article
  5. Treating Extensively Drug-ResistantPathogens (Basel, Switzerland) · 2026
    Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Mariya HuralskaDivision of Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.ORCID 0009-0007-5197-5966
Jason M PogueDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Michael RybakAnti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, Detroit, MI, USA.
Jacinda C Abdul-MutakabbirSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, USA.ORCID 0000-0003-4162-6408
Kyle StamperAnti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, Detroit, MI, USA.
Dror MarchaimUnit of Infection Control, Shamir (Assaf Harofeh) Medical Center, Be'er Ya'akov, Israel.
Visanu ThamlikitkulDivision of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.ORCID 0000-0002-0044-5988
Yehuda CarmeliNational Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Tel Aviv, Israel.
Cheng-Hsun ChiuDivision of Pediatric Infectious Diseases, Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chiayi County, Taiwan.ORCID 0000-0003-4324-7743
George DaikosSchool of Medicine, National and Kapodistrian University of Athens, Athen, Greece.ORCID 0000-0001-5365-4874
Sorabh DharDivision of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA.
Emanuele Durante-MangoniInternal Medicine, University of Campania 'L. Vanvitelli', and AORN dei Colli-Monaldi Hospital, Naples, Italy.ORCID 0000-0002-5381-3537
Achilles GikasDepartment of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, Stavrakia, Greece.
Anastasia KotanidouSchool of Medicine, National and Kapodistrian University of Athens, Athen, Greece.
Mical PaulInfectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel.ORCID 0000-0003-2317-1112
Emmanuel RoilidesInfectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University School of Health Sciences and Hippokration General Hospital, Thessaloniki, Greece.ORCID 0000-0002-0202-364X
Michael SamarkosFirst Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0001-9630-9712
Matthew SimsSection of Infectious Diseases and International Medicine, Department of Medicine, Corewell Health William Beaumont University Hospital, New York, NY, USA.
Dora TanchevaCentre for Burns and Plastic Surgery, Pirogov Emergency Medicine Hospital, Sofia, Bulgaria.
Sotirios Tsiodras4th Department of Internal Medicine, Attikon University Hospital, University of Athens Medical School, Athens, Greece.
Daniel H KettUniversity of Miami Hospital, Jackson Memorial Hospital, Miami, FL, USA.
Gopi PatelDivision of Infectious Diseases, Mount Sinai Hospital, New York, NY, USA.ORCID 0000-0003-1877-5608
David P CalfeeDivision of Infectious Disease, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0002-4647-790X
Leonard LeiboviciRabin Medical Center, Petah Tikva, Israel.
Laura PowerUniversity of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-9069-512X
Silvia Munoz-PriceEmerald Coast Infectious Diseases, Fort Walton Beach, FL, USA.
Hamadullah ShaikhDivision of Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Laura SusickDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.ORCID 0000-0002-1389-837X
Katie LatackDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
Christine ChiouNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
George DivineDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.ORCID 0000-0002-8465-0523
Varduhi GhazyaranNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Keith S KayeDivision of Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.ORCID 0000-0003-2051-1732

Funding

Division of Microbiology and Infectious Diseases 10-0065National Institute of Allergy and Infectious Diseases
6 · The paper itself

Abstract

backgroundColistin, 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.

methodsIn 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.

resultsA 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.

conclusionsColistin-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.

Indexed as

Anti-Bacterial AgentsBacteremiaColistinGram-Negative BacteriaGram-Negative Bacterial InfectionsMeropenemPneumonia, BacterialAgedCarbapenemsDrug Resistance, Multiple, BacterialDrug SynergismDrug Therapy, CombinationFemaleHumansMaleMicrobial Sensitivity TestsAnti-Bacterial AgentsCarbapenemsColistinMeropenemAcinetobacter baumanniiclinical failurecolistinmeropenemsynergy

Identifiers

PMID40682801
PMCPMC13016684

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.