Drugs 'boost' antibiotics

Treatment may allow lower dosages of antibiotics.

Booster drugs can improve the efficacy of some antibiotic therapy allowing smaller doses to be used without compromising treatment, research suggests.

Researchers in France examined the effect on treatment of TB with the antibiotic ethionamide, but they believe the principle could be used far more widely for reducing doses of antibiotics and other drugs.

As with a number of antibiotics, ethionamide is administered as a prodrug that must be metabolised before it becomes active against bacteria.

Dr Alain Baulard and his team at the Pasteur Institute in Lille developed inhibitors of the transcriptional factor that controls production of the enzyme that activates ethionamide.

In TB-infected mice, the use of one of these inhibitors enabled a small dose of ethionamide to treat infection as effectively as conventional high-dose treatment.

This approach could be used for other treatments administered as prodrugs.

'Our data suggest a rationale for the development of candidate molecules that could be used to boost the efficacy of several antimycobacterial drugs and limit their side-effects,' the researchers added.

'The approach illustrated here can be broadly applied to virtually any prodrug whose activation is under the genetic control of a transcriptional repressor,' the researchers said.

A dose-reduction approach has particular benefits in the case of ethionamide, since the drug has a number of dose-related adverse effects, such as nausea, vomiting and diarrhoea, which limit its use at high doses.

'Decreasing the dose without affecting the efficiency of the treatment should thus substantially increase the quality of life of the patients and, by consequence, the observance of the therapy,' the researchers said.

tom.moberly@haymarket.com

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