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1.
Microbios ; 76(309): 251-61, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8302203

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Quimioterapia Combinada/farmacologia , Mycobacterium/efeitos dos fármacos , Inibidores de beta-Lactamases , Amoxicilina/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio , Ampicilina/farmacologia , Animais , Ácidos Clavulânicos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium/enzimologia , Mycobacterium/crescimento & desenvolvimento , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam , Sulbactam/farmacologia
2.
J Infect Dis ; 163(6): 1374-7, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2037803

RESUMO

The activity of amoxicillin plus clavulanic acid against logarithmically multiplying Mycobacterium leprae was evaluated by treating mice by gavage five times weekly with various amounts of the compound from day 60 to day 150 after footpad infection. At 25, 50, and 100 mg/kg, it was inactive; at 200-600 mg/kg, multiplication of M. leprae was entirely prevented for 6-11 months after drug discontinuation, consistent with observations of bactericidal activity for M. leprae. In a confirmatory study in mice, five-times-weekly intraperitoneal ticarcillin plus clavulanic acid, 1000 mg/kg, was not bactericidal for M. leprae, while amoxicillin plus clavulanic acid, 400 mg/kg five times weekly, was weakly bactericidal (80% +/- 14%). In addition, activity of amoxicillin plus clavulanic acid, 400 mg/kg, was evaluated in combination with previously established active drugs dapsone, 0.0001% (in diet), rifampin, 20 mg/kg monthly (by gavage), and kanamycin, 25 mg/kg five times weekly (intraperitoneally). All three combinations were active, and the combination with kanamycin was more active than either drug alone.


Assuntos
Amoxicilina/farmacologia , Ácidos Clavulânicos/farmacologia , Hanseníase/tratamento farmacológico , Mycobacterium leprae/efeitos dos fármacos , Amoxicilina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio , Animais , Ácidos Clavulânicos/uso terapêutico , Dapsona/farmacologia , Dapsona/uso terapêutico , Quimioterapia Combinada/farmacologia , Quimioterapia Combinada/uso terapêutico , Canamicina/farmacologia , Canamicina/uso terapêutico , Cinética , Camundongos , Rifampina/farmacologia , Rifampina/uso terapêutico
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