Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)--a report of ten cases

Abstract

Objectives: Multidrug resistant tuberculosis (MDR-TB) is an increasing problem in many parts of the world and in Norway the increase has been substantial since 1998. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. The cure rate of this disease has been reported to be lower than for non-drug resistant TB, and the use of new experimental drugs in combination therapy is warranted.

Methods: Ten consecutive patients with culture proven MDR-TB were treated with the novel antibiotic drug linezolid in combination regimens for 6-40 (median 17) weeks and followed up 11-50 (median 24) months after end of treatment. All strains were sensitive to linezolid with MIC<4 mg/l. Treatment was given as direct observed therapy (DOT) and sputum cultures, blood chemistry and neurologic examination were undertaken on a regular basis.

Results: Nine patients were cured, one patient with poor adherence to treatment and advanced AIDS died. Seven of 10 patients experienced serious adverse events, which led to withdrawal of linezolid in all seven. Six patients developed peripheral neuropathy and five patients bone marrow depression, blood transfusions were given to three patients and in all five patients bone marrow function normalized after cessation of linezolid. Peripheral neuropathy was not fully reversed in all patients.

Conclusion: Linezolid seems highly active in combination treatment of MDR-TB. Cultures became negative 10-37 days after the introduction of the drug. However, peripheral neuropathy and bone marrow depression led to linezolid withdrawal in seven patients, and neuropathy may not be fully reversible in all patients.