Colistin Plus Meropenem Not Superior to Monotherapy for Carbapenem-Resistant Gram-Negative Bacteria

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Combination therapy increased the incidence of diarrhea and decreased the incidence of mild renal failure. <i>Photo Credit: CDC/ Janice Haney Carr.</i>
Combination therapy increased the incidence of diarrhea and decreased the incidence of mild renal failure. Photo Credit: CDC/ Janice Haney Carr.

The combination of colistin plus meropenem did not improve clinical failure in severe carbapenem-resistant bacterial infections compared with colistin monotherapy only, according to research published in the Lancet Infectious Diseases.

A randomized controlled superiority trial (ClinicalTrials.gov identifier: NCT01732250) was performed across 6 hospitals in Italy, Greece, and Israel in which 406 patients were randomly assigned to receive colistin or colistin plus meropenem. Of the 406 patients 87% had pneumonia or bacterimia, and 77% of all infections were caused by Acinetobacter baumannii.

Results indicated no significant difference in clinical failure (death or non-improving Sequential Organ Failure Assessment) after 14 days following randomization to either combination or monotherapy (risk difference –5.7%; 95% CI, –13.9-2.4; risk ratio [RR] 0.93; 95% CI, 0.83–1.03). The results were similar in patients with A baumannii (RR 0.97; 95% CI, 0.87-1.09).

Combination therapy did not result in better outcomes in this first randomized trial to address colistin plus meropenem combination therapy for carbapenem non-susceptible Gram-negative pathogens. The results do, however, relate mainly to the dominant bacteria in the cohort, A baumannii, as the study lacked the statistical power to address other bacteria.

The study was also not able to identify differences in the emergence of colistin resistance and did not use real-time drug measurements or central microbiology laboratory minimal inhibitory concentration determinations to direct treatment, although analysis of the latter is ongoing and will be presented in a separate report.

Future randomized trials are needed to “address different antibiotic strategies and patients subgroups, mainly infections caused by carbapenem-resistant K pneumoniae or other Enterobacteriaceae,”and this work “points to the necessity of assessing combination therapy in randomized trials before adopting it [into] in clinical use,” concluded the investigators. 

Reference

Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial [published online February 15, 2018]. Lancet Infect Dis. doi:10.1016/S1473-3099(18)30099-9

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