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, 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.
Prabhakaran
K
K
Laboratory Research Branch, GWL Hansen's Disease Center, Louisiana State University, Baton Rouge 70894-2059.
Harris
E B
EB
Randhawa
B
B
Adams
L B
LB
Williams
D L
DL
Hastings
R C
RC
D000658:Amoxicillin / Q000494:pharmacology; D019980:Amoxicillin-Potassium Clavulanate Combination; D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D013407:Sulbactam / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; C035444:sultamicillin; D019980:Amoxicillin-Potassium Clavulanate Combination; D000667:Ampicillin; D000658:Amoxicillin; D010397:Penicillanic Acid; D013407:Sulbactam; D010878:Piperacillin