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27-03-2012 | General practice | Article

Currently available antibiotics hold promise for treating drug resistant TB

Abstract

ACS website

MedWire News: Research suggests that a combination of two currently available antibiotics - meropenem and clavulanate - may be an effective treatment for tuberculosis (TB), particularly the hard to treat multi- and extensive-drug resistant (MDR and XDR) strains of the bacterium.

Presenting the data at the 243rd American Chemical Society National Meeting and Exposition in San Diego, California, USA, John Blanchard (Albert Einstein College of Medicine, Bronx, New York, USA) explained: "We've tested this combination against laboratory strains of Mycobacterium tuberculosis, XDR and MDR strains from patients.

"In all cases, the combination doesn't just slow down growth - it kills the bacterium in laboratory tests."

Standard treatment for TB involves taking a combination of four antibiotics (isoniazid, rifampin, pyrazinamidem, and ethambutol) for a period of 2 months, followed by a two-antibiotic combination (isoniazid and rifampin) for 4 months.

"As you can well imagine, after 40 or 45 years of people being treated with the same drugs, what's happening is that the bacterium is developing resistance to those drugs," commented Blanchard in a press statement.

"Some forms, or strains, are resistant to many drugs (MDR, or multidrug-resistant), and some are resistant to almost all known antibiotics (XDR, or extensively drug-resistant). A physician I know in India just reported a strain of TB that is totally drug-resistant. There's nothing currently available that he can use to treat these patients."

The basis of the current research was to find antibiotics that can resist or avoid the destructive effects of the beta-lactamase enzyme, which is produced by M.tuberculosis.

The team found that clavulanate irreversibly inactivates beta-lactamase and, if used in combination with a poor beta-lactam substrate such as meropenem, results in effective destruction of normal, MDR, and all 13 XDR strains of M. tuberculosis when tested in vitro.

In vivo trials of the new antibiotic combination in humans have not yet been carried out, but a recent case study suggests that the treatment is very promising.

"Clinical validation of our biochemical studies has come with the recent publication of a case study in which a 14 year-old girl was cured after 8 months of treatment," said Blanchard.

By Helen Albert

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