Atividade in vitro da combinação de rifampicina e verapamil em isolados de Mycobacterium tuberculosis multirresistentes

Abstract

The aim of this study was to evaluate the RIF and VP combination effect in MDR M tuberculosis clinical isolates and their ability to drug efflux. The time-kill curve assay was used to detect the synergic effect between the drugs and the inhibition of efflux pump effect was determined by ethidium bromide fluorometry. From six isolates, one (71A) had RIF and VP combination synergism with a decrease of more than two log10 CFU/mL. For the other five MDR clinical isolates, the drug combination showed to be additive. By EtBr accumulation assay two distinct profiles on the MDR isolates were observed. Isolates 18, 109 and 3614, showed a higher EtBr accumulation in VP alone and VP + RIF combination exposure and the isolates 71A, 64A and 19 showed a lower EtBr accumulation in VP + RIF combination exposure compared to a single drugs exposure. Coadjutants anti-TB therapy with VP for MDR M tuberculosis may render the bacillus to be more susceptible to RIF. However, additional studies are required in order to elucidate the safely and effectively therapeutic applications of the drug combination.