Can Colistin-Meropenem Synergy Combat Resistant Infections?

TOPLINE: 

Synergistic therapy combining colistin and meropenem reduced clinical failure rates in carbapenem-resistant infections and was particularly effective in Acinetobacter baumannii pneumonia cases. 

METHODOLOGY: 

• Researchers reported the findings from a secondary analysis of a randomized, double-blind trial that assessed the impact of synergistic therapy of colistin and meropenem on carbapenem-resistant pneumonia and/or bloodstream in adults.
• Overall, 407 patients (mean age, 68.0 years; 50.9% White; 63.5% men) were categorized into receiving synergistic combination therapy (n = 146) and functional monotherapy (n = 261) that included non-synergistic combination therapy and monotherapy.
• Outcomes of interest were 28-day all-cause mortality, clinical failure, and microbiologic cure.
• Clinical failure was defined as death during or within 7 days of treatment; rescue therapy initiation within 7 days of treatment; treatment discontinuation due to adverse events; persistent bacteremia > 5 days of treatment; or no improvement or worsening of oxygenation at treatment end in those with pneumonia.

TAKEAWAY:

• The most common pathogen was carbapenem-resistant A baumannii (n = 320) patients, followed by carbapenem-resistant Enterobacterales (n = 64) and carbapenem-resistant Pseudomonas aeruginosa (n = 41).
• Mortality rates did not differ significantly between the synergistic combination therapy and functional monotherapy groups (38.4% vs 41.4%); however, in the bloodstream infection subgroup, a trend toward reduced mortality was observed (adjusted odds ratio [aOR], 0.42; P = .054).
• In the pneumonia subgroup, synergistic combination therapy demonstrated significantly reduced clinical failure rates (62.6% vs 71.8%; aOR, 0.54; P = .04), and a similar but nonsignificant trend was observed in A baumannii infections (57.4% vs 69.4%; aOR, 0.60; P = .06).
• Microbiologic cure rates were similar between the study groups, with similar outcomes observed across subgroups defined by infection type and pathogen type.

IN PRACTICE:

“As synergism between colistin and meropenem is frequently present in A baumannii, when treating severe A baumannii infection with polymyxin-based therapy, consideration might be given to combination therapy with meropenem,” the authors wrote. 

SOURCE:

The study was led by Mariya Huralska, MD, from Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, and Jason M. Pogue, PharmD, from the University of Michigan College of Pharmacy in Ann Arbor. It was published online on July 19, 2025, in Clinical Infectious Diseases.

LIMITATIONS: 

The main limitation was that more than three quarters of the study pathogens were A baumannii, which limited the power to determine associations between synergy and outcomes for carbapenem-resistant Enterobacterales and P aeruginosa. Additionally, the findings might be applicable to polymyxin B; however, definitive conclusions cannot not be drawn as colistin was used in the trial. 

DISCLOSURES:

The study was supported by the National Institute of Allergy and Infectious Diseases. Some authors disclosed serving in consulting, advisory, or other financial support roles for Merck, Shionogi, Melinta, Entasis, GlaxoSmithKline, or VenatoRx. 

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