October 23, 2012
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Linezolid effective at culture conversion in XDR-TB

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Linezolid resulted in culture conversion among patients with treatment-refractory extensively drug-resistant tuberculosis but is associated with clinically significant adverse effects, according to researchers from the International Tuberculosis Research Center in Changwon, South Korea, and the Tuberculosis Research Section of the National Institute of Allergy and Infectious Diseases.

The study included 41 patients with sputum-culture–positive XDR-TB who were enrolled from December 2008 to May 2011. None of the patients had responded to other treatments, including isoniazid, rifampin, kanamycin, ofloxacin and moxifloxacin. The enrolled patients had been treated with a failing regimen for 6 months before enrollment.

In the phase 2a study, patients were randomly assigned to receive 600 mg per day of linezolid (Zyvox, Pfizer), besides their current treatment regimen, either immediately or after a 2-month delay. After 4 months or a confirmed sputum-smear conversion, the patients were randomly assigned again to continue linezolid at 600 mg a day or 300 mg a day for 18 months.

By 4 months, 79% of patients in the immediate-start group and 35% of the patients in the delayed-start group had negative sputum cultures on solid medium. When the groups were combined, 89% of patients had a culture conversion by 6 months.

However, 87% of patients had clinically significant adverse events, although only three patients permanently discontinued therapy. There were seven episodes of myelosuppression, seven cases of optic neuropathy, 21 cases of peripheral neuropathy and one case of rhabdomyolysis. After the second randomization, fewer people in the 300-mg dose group experienced adverse events.

Thirteen patients completed treatment and have not relapsed. Four patients developed resistance to linezolid.

“Although the small numbers of treatment failure and cases of acquired resistance are encouraging, they also preclude more in-depth analyses of the associated risk factors,” the researchers wrote. “Balancing the long-term risk-benefit ratio of linezolid requires identifying a dose with sufficient potency but less toxicity.”

Disclosure: The researchers report no relevant financial disclosures.