Combination of Existing Drugs Could Treat XDR-TB, Study Says

A combination of two existing antibiotics, clavulanate and meropenem, successfully blocked the growth of 13 extensively drug-resistant tuberculosis strains in laboratory tests, according to a study published Thursday in the journal Science, the AP/Los Angeles Times reports. XDR-TB is resistant to two of the most potent first-line treatments and at least two of the classes of second-line drugs. According to the AP/Times, researchers from NIH and New York's Montefiore Medical Center are planning to begin clinical trials of the drug combination in South Korea and South Africa later this year (Neergaard, AP/Los Angeles Times, 2/26).

For the study, John Blanchard of the Albert Einstein College of Medicine and colleagues examined the effectiveness of beta-lactam antibiotics, which include penicillin and are widely used to treat infections. This class of antibiotics never has treated TB successfully because the TB bacteria contain a highly active enzyme that inactivates these antibiotics. According to the study, the drug clavulanate successfully inhibits the expression of the TB enzyme, which allows meropenem, a fairly modern antibiotic, to kill the TB strain (BBC News, 2/27). The study found that the combination of clavulanate and meropenem was effective against 13 strains of XDR-TB in the laboratory.

GlaxoSmithKline sells clavulanate in combination with amoxicillin under the brand name Augmentin, and AstraZeneca sells meropenem as MERREM I.V., an intravenous antibiotic used for a range of bacterial infections. According to the researchers, both drugs are considered safe, and FDA has approved them for use in both adults and children (Dunham, Reuters, 2/26).

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Blanchard said the researchers are "excited" about the study's findings "because, with the caveat that this needs to be shown to be effective in controlled clinical trials, this would be the first new drug to be introduced in the treatment of TB in 40 years" (BBC News, 2/27). Brian Currie, also from the Einstein school, said the researchers "see tremendous potential for treating not only XDR-TB cases but also routine TB cases" (Reuters, 2/26). Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said the drug combination is "very clever" because when one drug blocks TB's defense mechanisms, "that leaves the original drug with the capability of doing what it's supposed to be doing" (AP/Los Angeles Times, 2/26).

Ruth McNerney, TB expert at the London School of Hygiene and Tropical Medicine, said health workers "desperately need drugs for XDR-TB" but added that the drug combination would need to undergo testing among humans before researchers could draw conclusions about its efficacy. Denis Mitchison, medical microbiologist at St. George's-University of London, said that the "combination now sounds effective" but that "there are already reports of rare resistant strains of other bacteria." Mitchison said health workers should exercise caution when using the drug combination as a single treatment to avoid the development of drug resistance. However, he added, "The more drugs that can be used in the treatment of multi-drug resistant and XDR-TB, the better" (BBC News, 2/27).

An abstract of the study is available online.