Colistin monotherapy more effective than combinations for treating drug resistant infections: NEJM

To treat pneumonia or bloodstream infections (BSI) brought on by extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE), colistin and meropenem combination therapy was not effective more than colistin monotherapy, says an article published in the New England Journal of Medicine. 

XDR Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and extensively drug-resistant Acinetobacter baumannii cause bloodstream infections and pneumonia that have high mortality rates and few effective treatments. Keith S. Kaye and colleagues tested whether colistin combination therapy was more effective than colistin monotherapy for treating these infections.

An multinational, double-blind, randomized, placebo-controlled experiment called OVERCOME (Colistin Monotherapy vs Combination Therapy) was conducted. For the treatment of pneumonia and/or BSI brought on by XDR A. baumannii, XDR P. aeruginosa, or CRE, we randomly allocated individuals to receive colistin (5 mg/kg once subsequently by 1.67 mg/kg every 8 hours) in conjunction with either meropenem (1000 mg every 8 hours) or matched placebo. 28-day mortality was the main endpoint, while clinical failing and microbiologic cure were the secondary outcomes.

The key findings of this study were:

A total of 464 individuals received therapy between 2012 and 2020; the modified intention-to-treat population included 423 eligible patients. 

The most prevalent trial pathogen (78%) was A. baumannii, and pneumonia was the most typical index illness (70%). 

When patients were enrolled, the majority (69%) were in the intensive care unit. 

Between patients receiving monotherapy and combination therapy, there was no difference in mortality (43 vs. 37%; P=0.17), clinical failure, microbiologic cure, or adverse events.

In conclusion, when compared to colistin monotherapy, receiving colistin + meropenem combination treatment had no effect on 28-day mortality, clinical failure, or microbiologic cure. The high rates of death and clinical failure in A. baumannii infections seen in both treatment arms of this trial show the urgent need for non-polymyxin therapeutic options for invasive infections brought on by this bacterium. Given the statistical trends toward decreased mortality in both OVERCOME and AIDA, further studies of the colistin plus meropenem combination for CRE and P. aeruginosa may be necessary.

Reference: 

Kaye, K. S., Marchaim, D., Thamlikitkul, V., Carmeli, Y., Chiu, C.-H., Daikos, G., Dhar, S., Durante-Mangoni, E., Gikas, A., Kotanidou, A., Paul, M., Roilides, E., Rybak, M., Samarkos, M., Sims, M., Tancheva, D., Tsiodras, S., Kett, D., Patel, G., … Pogue, J. M. (2022). Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms. In NEJM Evidence. Massachusetts Medical Society. https://doi.org/10.1056/evidoa2200131