The impact of colistin minimum inhibitory concentration on clinical failure and mortality: insights from the OVERCOME trial

OBJECTIVES: Colistin is an essential antibiotic against carbapenem-resistant Gram-negative bacilli. Pharmacokinetic and pharmacodynamic limitations impact its efficacy, and susceptibility breakpoints equivocate regarding interpretation of MIC values. This post hoc analysis of the OVERCOME trial investigated the association between colistin MIC and outcomes. METHODS: OVERCOME, a randomized, double-blind, placebo-controlled trial, compared colistin monotherapy with colistin plus meropenem for treatment of carbapenem-resistant Gram-negative bacilli pneumonia and/or bloodstream infections. Outcomes were compared between participants whose infections were caused by pathogens with colistin MIC values ≤1 mg/L and those with MIC values of 2 mg/L. RESULTS: Among 369 included participants, the mean age was 67.7 ± 15.9 years, 246 (67%) were in the intensive care unit, 251 (68%) had pneumonia, and 286 (78%) were infected with Acinetobacter baumannii. Overall, no association between an infecting pathogen with an MIC of 2 mg/L and either clinical failure (adjusted odds ratio [aOR]: 1.59 [95% CI: 0.72-3.52]) or 28-day mortality (aOR: 1.62 [95% CI: 0.85-3.09]) was demonstrated. Among participants receiving monotherapy, an infecting pathogen with an MIC of 2 mg/L was independently associated with both clinical failure (aOR: 3.59 [95% CI: 1.10-11.77]) and 28-day mortality (aOR: 3.22 [95% CI: 1.32-7.84]). Among participants receiving combination therapy, no association was demonstrated between MIC and outcomes. CONCLUSIONS: When using colistin-based therapy for pathogens with an MIC of 2 mg/L, these findings support colistin and meropenem combination therapy over colistin monotherapy, particularly for pneumonia due to A. baumannii.