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NIH Study: Antibiotic Shows Promise in Treating Drug-Resistant TB

Findings tempered by high rate of adverse events (Oct. 18)

The National Institutes of Health (NIH) have reported that linezolid, an antibiotic used to treat severe bacterial infections, was largely effective when added to ongoing treatment regimens in hospitalized patients with extensively drug-resistant tuberculosis (XDR-TB) that was unresponsive to previous therapies. In addition, few patients developed resistance to the drug.

These promising findings were tempered, however, by the fact that 82% of the patients who received linezolid experienced significant adverse events that may have been drug-related.

The study was conducted by researchers at the National Institute of Allergy and Infectious Diseases, part of the NIH, and was published in the October 18 issue of the New England Journal of Medicine.

XDR-TB is a form of TB that is resistant to at least four of the drugs most often used to treat the disease. Although XDR-TB is rare, 77 countries worldwide reported at least one case by the end of 2011, according to the World Health Organization. In the U.S., at least 57 cases of XDR-TB were reported between 1993 and 2010. Patients infected with XDR-TB typically have poor clinical outcomes, and with no effective drugs available for their treatment, they often die.

Researchers evaluated patients with chronic XDR-TB who had failed to respond to any treatment during the 6 months before enrollment into the study. The patients — predominantly men (72%) ranging in age from 20 to 64 years — were randomly assigned to begin immediate treatment with linezolid 600 mg once daily as part of their existing treatment regimen (19 patients) or to start the drug after a 2-month delay (20 patients). After they no longer tested positive for the bacterium or after 4 months of therapy, whichever came first, the patients were then randomly assigned for the next 18 months to continue taking either a daily 600-mg dose of linezolid or a daily 300-mg dose. The patients were regularly monitored for adverse effects.

After 4 months of treatment, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 patients (35%) in the delayed-start group no longer tested positive for TB. After 6 months of treatment, 34 of the 39 patients (87%) no longer tested positive for the bacterium.

Adverse effects associated with long-term linezolid use included bone-marrow suppression and peripheral and optic neuropathy. Thirty-one patients (82%) experienced clinically significant adverse events that were likely related to linezolid therapy, but most of these events resolved quickly after briefly stopping the drug or after using the lower 300-mg dose, the authors noted. Only three of the 31 patients (10%) permanently discontinued use of the drug because of side effects. In addition, only 4 of the 38 patients (11%) treated with linezolid for 6 months or more acquired resistance to the drug. Thirteen patients completed treatment and have not experienced a relapse in the 12 months after treatment ended. All of the patients continue to be watched for long-term outcomes.

The authors concluded that linezolid may become an important therapeutic option for patients with XDR-TB in the future. The drug may also form part of a regimen to treat MDR-TB in periods shorter than the 2 years of current standard therapy. However, in both instances, additional clinical trials are needed to identify a dosage that is sufficiently potent and yet does not cause significant adverse events, the authors said.

Source: NIH, October 18, 2012.

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