Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance?

Abstract

The use of high-dose isoniazid in retreatment regimens for tuberculosis, despite acquired isoniazid resistance, could possibly improve therapeutic results if all or part of the organisms were resistant to only low concentrations of that drug. Furthermore, organisms resistant to low concentrations of isoniazid have been shown, on occasion, to be resistant to 2 of the retreatment drugs, ethionamide and pyrazinamide, whereas higher degrees of isoniazid resistance are associated with susceptibility to these drugs. Use of high-dose isoniazid might improve results in retreatment with ethionamide and pyrazinamide by eliminating any organisms with low degrees of isoniazid resistance that have associated ethionamide and pyrazinamide resistance. Two clinical trials concerning this topic have been reported. A controlled retreatment trial with various combinations of ethionamide, cycloserine, and pyrazinamide with and without conventional "low" doses of isoniazid (300 mg per day) showed no benefit when isoniazid was added. However, a noncontrolled trial using ethionamide and pyrazinamide with and without high doses of isoniazid, 1 to 1.5 g per day, showed marked benefit with the added isoniazid. In view of these conflicting data, the use of high-dose isoniazid in retreatment regimens needs further study, which could probably be carried out in the developing countries.