Diabetes drug improves survival from life-threatening melioidosis infection
1 March 2011
Melioidosis, caused by a soil-dwelling bacterium (Burkholderia pseudomallei) that is present in certain regions of the world, results in severe infections including bloodstream infections and pneumonia. Death results in up to four out of ten affected individuals despite antibiotic treatment.
Now, in research published in the journal 'Clinical Infectious Diseases',an international team from the UK, Thailand, Singapore and the Netherlands has found that the diabetes drug glibenclamide (known as 'glyburide' in the USA) halves the risk of death in patients with melioidosis.
The investigators were supported by the Wellcome Trust South-east Asia Programme to study 1160 patients with melioidosis in northeast Thailand, and found that the number of deaths from melioidosis was only 28% in diabetic patients taking glyburide, compared to a mortality rate of nearly one in two in other patient groups, including those on other diabetes medication and people not affected by diabetes.
A study of white blood cells from people taking glibenclamide, performed by collaborators at the Wellcome Trust Sanger Institute, also showed less evidence of activity relating to inflammation.
“Our Thai collaborators realised several years ago that people with diabetes are more likely to get melioidosis, but are less likely to die from their infection compared with other people," says Dr Gavin Koh, from the University of Cambridge. "Our research shows that this improvement in survival is not an effect of diabetes itself, but of glibenclamide which is often prescribed to control the high blood sugar of diabetes.”
Glibenclamide does not seem to have a direct effect on the bacterium, and the researchers hypothesise that its benefit comes from modulating the human immune response to infection. This raises the important possibility that it might have the same benefit in people infected with other pathogens.
“Glibenclamide cannot be given safely to people who present to hospital with severe bacterial infection who do not have diabetes,” cautions Professor Sharon Peacock, senior investigator on the study, “but we hope that our findings will result in further research to define the mechanisms by which the drug increases patient survival, and to the development of related drugs that share these mechanisms but that do not lower blood sugar levels and can be given safely to all patients with severe sepsis.”
Image: Burkholderia pseudomallei grown on sheep blood agar for 48 hours. Credit: CDC/Courtesy of Larry Stauffer, Oregon State Public Health Laboratory.
Reference
Koh, GC et al. Glyburide Is anti-inflammatory and associated with reduced mortality in melioidosis. Clin Infect Dis; 3 Feb 2011
