TOPLINE:

Among patients with carbapenem-resistant gram-negative bacterial infections treated with colistin monotherapy, those infected with pathogens for which the colistin minimum inhibitory concentration (MIC) was 2 mg/L experienced worse clinical outcomes than those infected with pathogens for which the MIC was ≤ 1 mg/L.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the OVERCOME trial to assess the outcomes of colistin plus meropenem vs colistin plus placebo in treating pneumonia and/or bloodstream infections caused by carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, or carbapenem-resistant Enterobacterales.
• A total of 369 participants (mean age, 67.7 years; 62% men) from multiple countries were included, all of whom had index pathogens that were meropenem-resistant and colistin-susceptible (MIC ≤ 2 mg/L).
• They were randomly assigned to receive either colistin monotherapy (n = 185; 5 mg/kg colistin followed by 1.67 mg/kg colistin every 8 hours plus saline placebo) or combination therapy (n = 184; the same colistin regimen plus 1000 mg meropenem every 8 hours).
• Primary outcomes were clinical failure (evaluated in patients who survived ≥ 48 hours after enrollment) and 28-day mortality, which were compared between patients infected with pathogens for which the colistin MIC was ≤ 1 mg/L and those infected with pathogens for which the MIC was 2 mg/L.

TAKEAWAY:

• After adjustment for potential confounding factors, no significant association was found between a colistin MIC of 2 mg/L and clinical failure or 28-day mortality.
• Among participants receiving colistin monotherapy, infection with a pathogen for which the colistin MIC was 2 mg/L was independently associated with significantly higher rates of clinical failure (79% vs 60%; adjusted odds ratio [aOR], 3.59; 95% CI, 1.10-11.77) and 28-day mortality (61% vs 36%; aOR, 3.22; 95% CI, 1.32-7.84) than infection with a pathogen for which the colistin MIC was ≤ 1 mg/L.
• Among participants receiving colistin plus meropenem combination therapy, no significant differences in clinical failure rates or 28-day mortality were observed between participants infected with pathogens for which the colistin MIC was 2 mg/L and those infected with pathogens for which the MIC was ≤ 1 mg/L.

IN PRACTICE:

“These findings suggest that colistin and meropenem combination therapy is preferred over colistin monotherapy, particularly for A baumannii pneumonia, when the MIC value of the ‘susceptible’ infecting pathogen is 2 mg/L,” the authors wrote.

SOURCE:

The study was led by Jason M. Pogue, PharmD, University of Michigan College of Pharmacy, Ann Arbor, Michigan. These results were presented at the 33rd European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, Spain, in 2024. The study was published online on June 6, 2026, in Clinical Microbiology and Infection.

LIMITATIONS:

Although the data were derived from a randomized, double-blind, controlled trial, randomization was not stratified based on colistin MIC. Pharmacokinetic data were not assessed in OVERCOME, limiting the ability to directly ascertain the role of drug exposures in the observed findings. The small sample size of participants infected with pathogens for which the MIC was 2 mg/L (n = 48) limited the study’s statistical power.

DISCLOSURES:

This study received support from the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases. Several authors disclosed receiving financial support from pharmaceutical organizations, including Merck, AbbVie, Shionogi, CorMedix, and Entasis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.