EFFECT OF EFFLUX PUMP INHIBITORS ON RESISTANCE OF OFLOXACIN IN CLINICAL ISOLATES OF MYCOBACTERIUM TUBERCULOSIS

Bacterial efflux pump systems contribute to antimicrobial resistance in pathogenic bacteria. The coadministration of bacterial efflux pump inhibitors with antibiotics overcomes the efflux mediated resistance to antibiotics. In this study, we assessed the effect of efflux pump inhibitors on resistance levels of ofloxacin by minimal inhibitory concentration (MIC) and analyzed the extent of the efflux pump mediated ofloxacin drug resistance in clinical isolates of Mycobacterium tuberculosis. A total of 50 M. tuberculosis clinical isolates were tested to observe the decrease in MIC by the resazurinmicrotitre assay method in the presence and absence of efflux pump inhibitors; verapamil, carbonyl cyanide m-chlorophenylhydrazone, chloropromazine, 2-4 di-nitro phenol & reserpine. In this study, inhibitors exhibit efflux activity both in resistant and susceptible isolates to ofloxacin. However, they are seen to be more active in resistant isolates, since the MIC of ofloxacin studied in these isolates was reduced between 2- and 8-fold. Reduction in MIC of ofloxacin was achieved by more than one efflux pump inhibitors. Our findings suggest that the involvement of active efflux pumps alone can exist as an independent mechanism of resistance in M. tuberculosis isolates apart of mutations in gyrA&gyrB genes.