USE OF BETA-LACTAM BETA-LACTAMASE-INHIBITOR COMBINATIONS AS ANTIMYCOBACTERIAL AGENTS/

Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectivel y. Now multidrug-resistant tuberculosis is spreading in many countries , especially with the emergence of AIDS. Multidrug treatment is being promoted at present to eradicate leprosy. Since M. leprae may also bec ome multidrug-resistant, new approaches have to be adopted for control ling mycobacterial diseases. Mycobacteria usually synthesize beta-lact amase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamas e has been reported in M. leprae. Three different beta-lactam/beta-lac tamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavu lanate and piperacillin/tazobactam) were used to suppress the growth o f several strains of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam is a potent bactericidal agent against M. leprae multiplying in mouse foot pads. In the present work, ampicilli n/sulbactam showed higher activity than the other drug combinations. T he beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.