In-vitro and intracellular activity of rifabutin on drug-susceptible and multiple drug-resistant (MDR) tubercle bacilli

Rifabutin, a spiropiperidyl derivative of rifampicin, is approved for the prophylaxis of Mycobacterium avium infections in AIDS patients in the US, and for the treatment of M. avium infections, tuberculosis and multiple drug resistant tuberculosis in many countries. In the present study, rifabutin was compared with rifampicin for its activity against drug susceptible and multi-drug resistant tubercle bacilli by several in-vitro and macrophage studies. Rifabutin exhibited similar or greater in-vitro activity than rifampicin as judged by the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and MBC/MIC ratios, as well as continuous exposure and post-antibiotic effect studies. Rifabutin has been shown to be active against some multiple drug resistant strains which were resistant to rifampicin. In macrophage studies with continuous exposure to the drug or when the drug had been removed after 24 h, rifabutin also demonstrated high activity which was better than RMP against intracellular tubercle bacilli. This long-acting intracellular anti-mycobacterial activity may explain, in part, the clinical efficacy of rifabutin.