Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil.

摘要: Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. clinical isolates presenting efflux as part their phenotype has a major impact in treatment. In this work, we used checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) study single combinations between antituberculosis drugs inhibitors (EIs) against multidrug using fully susceptible strain H37Rv reference. Efflux activity was studied on real-time basis by fluorometric method that uses ethidium bromide substrate. Quantification pump genes mRNA transcriptional levels were performed RT-qPCR. fractional inhibitory concentrations (FIC) indicated synergistic interactions isoniazid, rifampicin, amikacin, ofloxacin, plus EIs verapamil, thioridazine chlorpromazine. FICs ranged from 0.25, indicating four-fold reduction MICs, 0.015, 64-fold reduction. detection active fluorometry showed all strains presented intrinsic contributes overall resistance which can be inhibited presence EIs. quantification most important these shows they intrinsically predisposed expel toxic compounds exposure subinhibitory antibiotics not necessary when compared non-exposed counterpart. results obtained confirm inhibition pumps enhance effect substrates.