Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis

Objectives: Although linezolid has good in vitro activity against Mycobacterium tuberculosis, its long-term use in the treatment of multidrug-resistant tuberculosis (MDR-TB) may be limited by its cost and serious adverse reactions. We therefore evaluated the efficacy and tolerability of a reduced dose of linezolid, in combination with other anti-TB drugs, in patients with intractable or extensive MDR-TB. Methods: MDR-TB patients unresponsive to at least three cycles of treatment were treated with daily-half doses of linezolid (600 mg once per day) plus at least four companion drugs. Results: As of March 2006, eight patients, all HIV-negative, had been treated with linezolid for 3-18 months. Cultures became negative in all patients in an average of 82 days. Four patients developed peripheral neuropathy, two developed optic neuropathy and one developed anaemia. Although optic neuropathy resolved after cessation of linezolid therapy, peripheral neuropathy continued. One patient completed 18 months of linezolid therapy. Two patients, who have taken linezolid for 15-17 months, are still on treatment and remain in culture conversion. Three patients stopped linezolid after 7-9 months, two because of side effects and one for economic reasons, but remain on treatment with other second-line drugs with culture conversion. Two patients died from severe respiratory failure, but both previously had shown culture conversion. Conclusions: Although daily-half doses of linezolid were effective in patients with intractable or extensive MDR-TB, this dosage regimen did not reduce long-term use-related side effects, such as peripheral and optic neuropathy.