02265nas a2200373 4500000000100000008004100001260000900042653001600051653005000067653001500117653001200132653002600144653002100170653003000191653000900221653003200230653001800262653002200280653001700302653004600319653001400365653003000379100001800409700001500427700001500442700001400457700001700471700001700488245009000505300001100595490000700606520126400613022001401877 1993 d c199310aAmoxicillin10aAmoxicillin-Potassium Clavulanate Combination10aAmpicillin10aAnimals10aAnti-Bacterial Agents10aClavulanic Acids10aDrug Therapy, Combination10aMice10aMicrobial Sensitivity Tests10aMycobacterium10aPenicillanic Acid10aPiperacillin10aPiperacillin, Tazobactam Drug Combination10aSulbactam10abeta-Lactamase Inhibitors1 aPrabhakaran K1 aHarris E B1 aRandhawa B1 aAdams L B1 aWilliams D L1 aHastings R C00aUse of beta-lactam/beta-lactamase-inhibitor combinations as antimycobacterial agents. a251-610 v763 a

Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. 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 become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. Mycobacteria usually synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamase has been reported in M. leprae. Three different beta-lactam/beta-lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam) were used to suppress the growth of 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, ampicillin/sulbactam showed higher activity than the other drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.

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