ENHANCEMENT OF DRUG SUSCEPTIBILITY OF MULTIDRUG-RESISTANT STRAINS OF MYCOBACTERIUM-TUBERCULOSIS BY ETHAMBUTOL AND DIMETHYL-SULFOXIDE

Strategies to augment conventional methods of drug delivery in treatme nt of multiple drug resistant tuberculosis are needed to achieve optim um results with available drugs. We have studied the effect of sub-min imum inhibitory concentrations (sub-MIG) of ethambutol and dimethyl su lphoxide on drug susceptibility of Mycobacterium tuberculosis strains both in vitro and in macrophages. At sub-MIG ethambutol between caused four and 64 fold increase in susceptibility to isoniazid rifampicin a nd streptomycin in four M. tuberculosis strains, resistant to these dr ugs. Incubation of the organisms with isoniazid and sub-MIG of dimethy l sulphoxide (2.5%) resulted in an eight-fold increase in susceptibili ty to the drug. Previous exposure of the organisms to sub-MIG of dimet hyl sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIG of sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dime thyl sulphoxide at the sub-MIG enhanced the activity of the anti-tuber culosis drugs against multiple drug resistant M. tuberculosis strains growing inside macrophages. Our data indicate that the agents which mo dify cell wall permeability can enhance the susceptibility of multiple drug resistant strains to drugs to which they were originally resista nt. This could provide a new approach to treating drug resistant tuber culosis.