MULTIDRUG-RESISTANCE IN MYCOBACTERIUM-TUBERCULOSIS

All but one of the four major mechanisms of resistance to antimicrobia l agents-inactivation of the drug, altered cell wall permeability or d rug efflux, drug titration due to target overproduction, and alteratio n of the target by mutation-appear to be employed by Mycobacterium tub erculosis in its resistance to components of short course chemotherapy regimens. To date no enzymes capable of inactivating any of the front line drugs have been found. The most common resistance mechanism is al teration of the target leading to inadequate drug binding, or drug act ivation: as a result of mutations in chromosomal genes. This occurs in the case of the specific antituberculous drugs isoniazid, pyrazinamid e and ethionamide as well as in resistance to the broad-spectrum antib iotics, rifampicin, streptomycin and the fluoroquinolones. Overproduct ion of the drug target also appears to lead to resistance to isoniazid and ethionamide whereas changes in permeability, or the activation of antibiotic-efflux systems, may contribute to the low-level resistance of the tubercle bacillus to streptomycin and fluoroquinolones. (C) 19 97 Elsevier Science B.V.