IN-VITRO AND IN-VIVO SYNERGISTIC EFFECT OF ISONIAZID WITH STREPTOMYCIN AND CLOFAZIMINE AGAINST MYCOBACTERIUM-AVIUM COMPLEX (MAC)

Setting: Isoniazid (INH), the powerful antituberculosis drug, has also been used in regimens for treating disease caused by Mycobacterium av ium complex (MAC), an important opportunistic pathogen encountered in AIDS patients. Its use for treatment of MAC disease has also been endo rsed by the American Thoracic Society. However some controversy has em erged recently in medical literature, discounting its role and even im plying that its use is contraindicated in chemotherapy of MAC disease. Objective: In view of the controversy, we investigated its in vitro a nd in vivo activity in combination with streptomycin (SM) and clofazim ine (CFM) against MAC. Design: In the in vitro studies, the minimal in hibitory concentrations (MIC) of individual drugs or combinations of I NH and SM as well as INH and CFM were determined in a checker-board ty pe studv by both conventional and radiometric (BACTEC) methods. In viv o studies assessed the efficacy of chemotherapy with INH alone or in c ombination with either SM or CFM against MAC infection in beige mice. Results and conclusions: While MICs of INH and SM were 12.5 mug/ml and 6.25 mug/ml respectively, complete inhibition of growth was seen at 1 .56 mug/ml with the combination of both drugs. The synergistic effect was observed both in conventional and BACTEC methods. In vivo studies demonstrated elevated activity when INH was given along with SM or CFM . Based on these observations we stress that isoniazid has still a pla ce in chemotherapy of MAC disease, at least until other potent drugs a re discovered.