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1.
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
3.
Antimicrob Agents Chemother ; 39(9): 2116-9, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8540726

RESUMO

The in vitro susceptibility of Mycobacterium leprae to levofloxacin was studied by using two biochemical parameters to measure the metabolic activity of the organism. Levofloxacin consistently exhibited twofold greater bactericidal activity than ofloxacin, with the MIC being 0.75 microgram/ml. When combined with one of the three rifamycin analogs, synergism was obtained with KRM-1648 and rifabutin but not with rifampin.


Assuntos
Anti-Infecciosos/farmacologia , Quimioterapia Combinada/farmacologia , Levofloxacino , Mycobacterium leprae/efeitos dos fármacos , Ofloxacino/farmacologia , Trifosfato de Adenosina/metabolismo , Antibacterianos/farmacologia , Meios de Cultura , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Mycobacterium leprae/metabolismo , Rifamicinas/farmacologia , Timidina/metabolismo
4.
Nihon Kyobu Shikkan Gakkai Zasshi ; 32(11): 1078-82, 1994 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-7815761

RESUMO

An 80-year-old blind man with lepromatous leprosy suffered from right femoral neck and humeral neck fractures on July 9, 1993. Because of fever (38.6 degrees C), difficult expectoration and diffuse bilateral perihilar infiltrates with consolidation in the left lower lung field on his chest radiograph, severe pneumonia was diagnosed. With intravenous hyperalimentation, imipenem/cilastatin (IPM/CS), ceftazidime, minocycline, gentamicin (GM), and human immunoglobulin were administrated. On July 29, hip screw-plate fixation was done. Citrobacter freundii was isolated from the sputum and its susceptibility was IPM/CS+, GM3+. Multi-drug therapy with GM and other antibiotics improved the patients' condition, but Citrobacter freundii were still detected and 43 days of medication were needed. According to a report by the Ministry of Health and Welfare in 1992, the resistance rate of IPM/CS against Citrobacter freundii is only 0.7%, and IPM/CS is more effective than beta-Lactams. This is a very rare case of severe pneumonia in an elderly patient caused by Citrobacter freundii that was suspected to have low susceptibility to IPM/CS.


Assuntos
Citrobacter freundii/efeitos dos fármacos , Quimioterapia Combinada/farmacologia , Infecções por Enterobacteriaceae/microbiologia , Pneumonia Bacteriana/microbiologia , Idoso , Idoso de 80 Anos ou mais , Cilastatina/farmacologia , Combinação Imipenem e Cilastatina , Citrobacter freundii/isolamento & purificação , Combinação de Medicamentos , Resistência Microbiana a Medicamentos , Infecções por Enterobacteriaceae/tratamento farmacológico , Gentamicinas/uso terapêutico , Humanos , Imipenem/farmacologia , Masculino , Pneumonia Bacteriana/tratamento farmacológico
5.
Int J Lepr Other Mycobact Dis ; 62(1): 37-42, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8189087

RESUMO

The anti-Mycobacterium leprae activities of single doses of rifampin (RMP), clarithromycin (CLARI), or minocycline (MINO) alone, and various combinations of CLARI + MINO were determined in immunocompetent mice by the kinetic method. A single dose of RMP 10 mg/kg, CLARI 100 mg/kg or 200 mg/kg, MINO 25 mg/kg or 50 mg/kg alone, or various combinations of CLARI & MINO were active. RMP was more active than the other treatments; the activity of CLARI 100 mg/kg was greater than that of 50 mg/kg, but did not differ significantly from that of 200 mg/kg; MINO 50 mg/kg was more active than 25 mg/kg; and none of the combinations of CLARI + MINO was more active than any of the stronger components administered alone. Therefore, both CLARI and MINO may be applied, either alone or in combination, as components of monthly administered, fully supervised, multidrug regimens for the treatment of multibacillary leprosy. Taking into account the effectiveness of the drugs and the comparative pharmacokinetic data, we propose that the optimal dosage in human trials is CLARI 1000 mg per month or MINO 200 mg per month.


Assuntos
Claritromicina/farmacologia , Minociclina/farmacologia , Mycobacterium leprae/efeitos dos fármacos , Animais , Claritromicina/administração & dosagem , Quimioterapia Combinada/farmacologia , Feminino , Camundongos , Minociclina/administração & dosagem , Mycobacterium leprae/crescimento & desenvolvimento
6.
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
7.
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
8.
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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