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1.
Int J Antimicrob Agents ; 13(2): 133-5, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10595573

RESUMO

The resistance of mycobacteria to beta-lactam antibiotics is attributed to their ability to synthesize beta-lactamase. In our previous studies, beta-lactam/beta-lactamase-inhibitor combinations suppressed the growth of several mycobacteria in axenic cultures and ampicillin/sulbactam was bactericidal to Mycobacterium tuberculosis H37Rv in vitro, and to Mycobacterium leprae multiplying in mouse foot-pads. Since both these organisms multiply in phagocytic cells in the host, it is important to know whether the drug combination is active against mycobacteria multiplying in macrophages. We tested the action of ampicillin/sulbactam against four potentially pathogenic (to humans or to animals) mycobacteria, M. simiae, M. haemophilum, M. avium, M. microti, when phagocytosed by mouse macrophages. Bacteria were exposed to monolayers of peritoneal macrophages harvested from BALB/c mice. Unphagocytosed bacilli were removed and three concentrations of ampicillin/sulbactam were tested. Optimum activity was observed at 100 mg/l which killed 58-97% of the mycobacteria within macrophages, as determined by the CFU. beta-Lactam/beta-lactamase-inhibitors, especially ampicillin/sulbactam, might provide an effective alternative therapy against infections caused by mycobacteria resistant to other drugs.


Assuntos
Ampicilina/farmacologia , Inibidores Enzimáticos/farmacologia , Mycobacterium/efeitos dos fármacos , Penicilinas/farmacologia , Sulbactam/farmacologia , Inibidores de beta-Lactamases , Animais , Contagem de Colônia Microbiana , Interações Medicamentosas , Humanos , Técnicas In Vitro , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium/crescimento & desenvolvimento , Fagocitose
2.
J Antimicrob Chemother ; 44(2): 279-81, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10473236

RESUMO

We reported previously that an injectable form of ampicillin/sulbactam, Unasyn, was bactericidal to Mycobacterium leprae multiplying in mouse foot pads. In this study, we examined the effect of an orally active form of ampicillin/sulbactam, Sultamicillin, on the growth of M. leprae in mice. Three concentrations of the drug, mixed with the feed, were administered from the start until the mice were killed at 6 months; 0.01% of the drug inhibited bacterial growth by 54%, 0.10% by 74% and 0.20% by 93%. To test whether oral ampicillin/sulbactam was bactericidal, 0.50% of the drug, mixed with the feed, was administered to experimentally infected mice for 3 months during the logarithmic phase of bacterial growth, and then discontinued; multiplication of the bacilli was monitored monthly for the next 8 months. The results showed that orally active ampicillin/sulbactam is bactericidal to M. leprae.


Assuntos
Quimioterapia Combinada/farmacologia , Mycobacterium leprae/efeitos dos fármacos , Administração Oral , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Animais , Quimioterapia Combinada/administração & dosagem , Membro Posterior/microbiologia , Hanseníase/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Mycobacterium leprae/crescimento & desenvolvimento , Sulbactam/administração & dosagem , Sulbactam/farmacologia
4.
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
5.
Microbios ; 72(291): 137-42, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1287401

RESUMO

The multiplication of Mycobacterium leprae in foot pads of experimentally-infected mice was suppressed by intramuscular administration of ampicillin combined with sulbactam or YTR-830H, two potent inhibitors of beta-lactamase in the bacteria. The antibiotic or the inhibitors by themselves were inactive. Ampicillin/sulbactam also inhibited the growth of drug-resistant M. leprae which grew in the presence of rifampin or dapsone. The finding provides a new approach to treat leprosy and to overcome drug resistance of the mycobacteria.


Assuntos
Ampicilina/farmacologia , Mycobacterium leprae/efeitos dos fármacos , Sulbactam/farmacologia , Animais , Resistência Microbiana a Medicamentos , Quimioterapia Combinada/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium leprae/crescimento & desenvolvimento
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