title: Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide.
abstract: Strategies to augment conventional methods of drug delivery in treatment of multiple drug resistant tuberculosis are needed to achieve optimum results with available drugs. We have studied the effect of sub-minimum inhibitory concentrations (sub-MIC) of ethambutol and dimethyl sulphoxide on drug susceptibility of Mycobacterium tuberculosis strains both in vitro and in macrophages. At sub-MIC ethambutol between caused four and 64 fold increase in susceptibility to isoniazid rifampicin and streptomycin in four M. tuberculosis strains, resistant to these drugs. Incubation of the organisms with isoniazid and sub-MIC of dimethyl sulphoxide (2.5%) resulted in an eight-fold increase in susceptibility to the drug. Previous exposure of the organisms to sub-MIC of dimethyl sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC of sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC enhanced the activity of the anti-tuberculosis drugs against multiple drug resistant M. tuberculosis strains growing inside macrophages. Our data indicate that the agents which modify cell wall permeability can enhance the susceptibility of multiple drug resistant strains to drugs to which they were originally resistant. This could provide a new approach to treating drug resistant tuberculosis.
authors.affiliation: Department of Medicine, University of Illinois, Chicago 60612, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jagannath
authors.forename: V M
authors.initials: VM
authors.lastname: Reddy
authors.forename: P R
authors.initials: PR
authors.lastname: Gangadharam
mesh_terms: D002460:Cell Line; D002473:Cell Wall / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010539:Permeability; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin; D004121:Dimethyl Sulfoxide