Untreatable cases of extensively drug-resistant tuberculosis (XDR-TB) could be tackled with a combination of two existing drugs — one of which was developed over 30 years ago.
Laboratory studies, published in Science last week (27 February), showed that a combination of the drugs meropenem and clavulanate inhibited the growth of 13 separate strains of XDR-TB.
They also inhibited the growth of drug-susceptible laboratory strains and those that mimic the 'latent' state of TB — an inactive phase of TB which is difficult to treat.
The researchers, from the US National Institute of Allergy and Infectious Diseases and the US-based Albert Einstein College of Medicine, are optimistic that if the results are reproduced in humans, an effective XDR-TB treatment could be produced in a relatively short time.
Meropenem belongs to a class of antibiotics called b-lactams. These widely-used drugs have never proved useful in TB treatment as Mycobacterium tuberculosis possesses an enzyme that breaks them down. But clavulanate inhibits the enzyme, allowing meropenem to kill M. tuberculosis when the two are used in combination.
Phase II clinical trials of the drug combination will commence on about 100 patients in South Korea by the end of the year.
A smaller trial on 15–20 TB patients in South Africa — half of whom will also be HIV-infected — will hopefully begin by mid-2009, says Brian Currie, professor of medicine at the Albert Einstein College of Medicine who will design and run the trial, along with Willem Sturm, dean of the Nelson Mandela School of Medicine in Durban, South Africa.
Currie says South Africa was chosen as a test site due to its high prevalence of XDR-TB.
He told SciDev.Net that clavulanate was not yet approved in South Africa and the trials would instead use an oral preparation of amoxicillin-clavulanate, which is approved, along with meropenem.
This combination was also tested in the current research, and while not as effective as meropenem and clavulanate, it is still superior to other drugs, says Currie, and its use will bypass an estimated 12-month delay before preparations of clavulanate are approved.