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1.
PLoS One ; 15(4): e0231320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267877

RESUMO

INTRODUCTION: Tuberculosis (TB) remains a major global public health problem and is the leading cause of death from a single bacterium, Mycobacterium tuberculosis (MTB) complex. The emergence and spread of drug-resistant strains aggravate the problem, especially in tuberculosis high burden countries such as Ethiopia. The supposedly high initial cost of laboratory diagnosis coupled with scarce financial resources has limited collection of information about drug resistance patterns and circulating strains in peripheral and emerging regions of Ethiopia. Here, we investigated drug susceptibility and genetic diversity of mycobacterial isolates among pulmonary tuberculosis patients in the Benishangul Gumuz region and its surroundings in northwest Ethiopia. METHODS AND MATERIAL: In a cross-sectional study, 107 consecutive sputum smear-positive pulmonary tuberculosis (PTB) patients diagnosed at two hospitals and seven health centers were enrolled between October 2013 and June 2014. Sputum samples were cultured at Armauer Hansen Research Institute (AHRI) TB laboratory, and drug susceptibility testing (DST) was performed against Isoniazid, Rifampicin, Ethambutol, and Streptomycin using the indirect proportion method. Isolates were characterized using polymerase chain reaction (PCR)based Region of Difference 9 (RD9) testing and spoligotyping. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) for Windows version 24.0. RESULTS: Of 107 acid-fast-bacilli (AFB) smear-positive sputum samples collected, 81.3% (87/107) were culture positive. A PCR based RD9 testing revealed that all the 87 isolates were M. tuberculosis. Of these isolates, 16.1% (14/87) resistance to one or more drugs was observed. Isoniazid monoresistance occurred in 6.9% (6/87). Multidrug resistance (MDR) was observed in two isolates (2.3%), one of which was resistant to all the four drugs tested. Spoligotyping revealed that the majority, 61.3% (46/75) of strains could be grouped into ten spoligotype patterns containing two to 11 isolates each while the remaining 38.7% (29/75) were unique. SIT289 (11 isolates) and SIT53 (nine isolates) constituted 43.5% (20/46) among clustered isolates while 29.3% (22/75) were ''New" to the database. The dominant families were T, 37% (28/75), CAS, 16.0% (12/75), and H, 8% (6/75), adding up to 51.3% (46/75) of all isolates identified. CONCLUSION AND RECOMMENDATIONS: The current study indicates a moderate prevalence of MDR TB. However, the observed high monoresistance to Isoniazid, one of the two proxy drugs for MDR-TB, reveals the hidden potential threat fora sudden increase in MDR-TB if resistance to Rifampicin would increase. Clustered spoligotype patterns suggest ongoing active tuberculosis transmission in the area. The results underscore the need for enhanced monitoring of TB drug resistance and epidemiological studies in this and other peripheral regions of the country using robust molecular tools with high discriminatory power such as the Mycobacterial Interspersed Repetitive Units -Variable Number of Tandem Repeats (MIRU-VNTR) typing and whole-genome sequencing (WGS).


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Variação Genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Etambutol/farmacologia , Etiópia/epidemiologia , Feminino , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
2.
Lab Chip ; 14(11): 1850-7, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24756475

RESUMO

Persistence of bacteria during antibiotic therapy is a widespread phenomenon, of particular importance in refractory mycobacterial infections such as leprosy and tuberculosis. Persistence is characterized by the phenotypic tolerance of a subpopulation of bacterial cells to antibiotics. Characterization of these "persister" cells is often difficult due to the transient, non-heritable nature of the phenotype and due to the presence of contaminating material from non-persisting cells, which usually comprise the larger fraction. In this study, we use 3D carbon-electrode arrays for dielectrophoresis-based separation of intact cells from damaged cells, revealed by differential staining with propidium iodide, and we use this procedure to purify intact cells from cultures of Mycobacterium smegmatis treated with isoniazid, a frontline anti-tuberculosis drug. The method presented in this study could be used for rapid label-free enrichment of intact persister cells from antibiotic-treated cultures while preserving the metastable persister phenotype. This approach would facilitate the downstream analysis of low-frequency subpopulations of cells using conventional omics techniques, such as transcriptomic and proteomic analysis.


Assuntos
Antituberculosos/farmacologia , Isoniazida/farmacologia , Mycobacterium smegmatis/citologia , Corantes/farmacologia , Eletroforese/métodos , Mycobacterium smegmatis/metabolismo , Propídio/farmacologia
3.
Nihon Hansenbyo Gakkai Zasshi ; 82(3): 119-22, 2013 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-24579459

RESUMO

Instead of rapid multiplication, pathogenic mycobacteria, such as Mycobacterium tuberculosis are likely to have acquired slow but long life. Host immunity affords desirable non-competitive environment for M tuberculosis in human lungs, where this pathogen slowly grows or arrests growing, which avoids rapid loss of living places. Mycobacterial DNA-binding protein 1 (MDP1), a unique histone-like protein associating mycobacterial GC-rich DNA, has pivotal role in realizing such slow life and pathogenesis including drug tolerance to isoniazid.


Assuntos
Antituberculosos/farmacologia , Fenômenos Fisiológicos Bacterianos/genética , Farmacorresistência Bacteriana/genética , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Animais , Proteínas de Bactérias/fisiologia , Proteínas de Ligação a DNA/fisiologia , Humanos , Pulmão/microbiologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade
4.
Arzneimittelforschung ; 57(7): 472-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17803061

RESUMO

Tissue distribution and deposition of clofazimine (CAS 2030-63-9) in mice were investigated following administration of clofazimine with or without isoniazid (CAS 54-85-3). Balb/c mice were administered clofazimine suspension in mustard oil orally at a daily dose of 20 mg/kg body weight either alone or along with isoniazid (10 mg/kg body weight) for 15 or 30 days. Various tissues (liver, lung, spleen, small intestine, heart, kidneys, mesentric fat, foot pad and nerve) and pooled plasma were analysed for clofazimine in all the treated groups. High levels of clofazimine were observed in tissues having reticulo-endothelial components (53-263 microg/g wet tissue). In other tissues the levels of the drug were relatively lower (8.1-42.8 microg/g of wet tissue). There was a significant amount of the drug in foot pads and pooled nerve tissue showed detectable amount of the drug. The plasma concentrations in all treated groups were in the range of 0.5-0.8 microg/ml. Tissue levels were found to be increased in selective tissues with the length of drug administration. Concomitant administration of isoniazid reduced clofazimine levels significantly in tissues like small intestine, spleen, and foot pad and resulted in an increase in plasma levels.


Assuntos
Clofazimina/farmacocinética , Isoniazida/farmacologia , Hansenostáticos/farmacologia , Hansenostáticos/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Densitometria , Interações Medicamentosas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Tecidual
5.
J Med Microbiol ; 50(8): 675-681, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11478670

RESUMO

As Mycobacterium leprae proliferate inside macrophages, it has been speculated that catalase encoded by katG may protect the bacilli from deleterious effects of peroxide generated from the macrophage and may also play a crucial role in the survival of M. leprae in vivo. However, unlike that of M. tuberculosis, the katG of M. leprae has been reported to be a pseudogene, implicating that isoniazid, which is activated to a potent tuberculocidal agent by catalase, is unlikely to be of therapeutic benefit to leprosy patients. These results raise a question as to how M. leprae avoids H202-mediated killing inside macrophages. To understand the survival of M. leprae in macrophages, the present study attempted to detect catalase-like activity in M. leprae. Catalase-like activity was found in M. leprae cell lysate by the diaminobenzidine (DAB) staining method with non-denaturing polyacrylamide gel electrophoresis. An ammonium sulphate precipitation study revealed that the catalase-like activity was precipitable with 80% ammonium sulphate. The effect of isoniazid (INH) on M. leprae growth was also tested by RT-PCR and radiorespirometric assay to examine catalase-like activity in M. leprae, because INH was activated by catalase. It was found that the viability of M. leprae was decreased at a concentration of 20 microg/ml by radiorespirometric assay and it was inhibited at higher concentrations as determined by RT-PCR. These data suggest that a catalase-like activity other than that encoded by katG is present in M. leprae.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias , Catalase/metabolismo , Isoniazida/farmacologia , Mycobacterium leprae/enzimologia , Peroxidases/metabolismo , Sulfato de Amônio , Animais , Sequência de Bases , Benzidinas , Catalase/genética , Primers do DNA , DNA Complementar/análise , Eletroforese em Gel de Ágar , Peróxido de Hidrogênio/metabolismo , Hanseníase/tratamento farmacológico , Hanseníase/enzimologia , Macrófagos Peritoneais/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/genética , Peroxidases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Contagem de Cintilação , Homologia de Sequência do Ácido Nucleico , Espectrofotometria
7.
Infect Immun ; 65(4): 1395-401, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9119479

RESUMO

Mutations to the regulatory region of the ahpC gene, resulting in overproduction of alkyl hydroperoxide reductase, were encountered frequently in a large collection of isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis but not in INH-susceptible strains. Overexpression of ahpC did not seem to be important for INH resistance, however, as most of these strains were already defective for catalase-peroxidase, KatG, the enzyme required for activation of INH. Transformation of the INH-susceptible reference strain, M. tuberculosis H37Rv, with plasmids bearing the ahpC genes of M. tuberculosis or M. leprae did not result in a significant increase in the MIC. Two highly INH-resistant mutants of H37Rv, BH3 and BH8, were isolated in vitro and shown to produce no or little KatG activity and, in the case of BH3, to overproduce alkyl hydroperoxide reductase as the result of an ahpC regulatory mutation that was also found in some clinical isolates. The virulence of H37Rv, BH3, and BH8 was studied intensively in three mouse models: fully immunocompetent BALB/c and Black 6 mice, BALB/c major histocompatibility complex class II-knockout mice with abnormally low levels of CD4 T cells and athymic mice producing no cellular immune response. The results indicated that M. tuberculosis strains producing catalase-peroxidase were considerably more virulent in immunocompetent mice than the isogenic KatG-deficient mutants but that loss of catalase-peroxidase was less important when immunodeficient mice, unable to produce activated macrophages, were infected. Restoration of virulence was not seen in an INH-resistant M. tuberculosis strain that overexpressed ahpC, and this finding was confirmed by experiments performed with appropriate M. bovis strains in guinea pigs. Thus, in contrast to catalase-peroxidase, alkyl hydroperoxide reductase does not appear to act as a virulence factor in rodent infections or to play a direct role in INH resistance, although it may be important in maintaining peroxide homeostasis of the organism when KatG activity is low or absent.


Assuntos
Antituberculosos/farmacologia , Resistência Microbiana a Medicamentos/genética , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Isoniazida/farmacologia , Mycobacterium tuberculosis/enzimologia , Oxirredutases/biossíntese , Peroxidases , Animais , Sequência de Bases , Camundongos , Dados de Sequência Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Oxirredutases/genética , Peroxirredoxinas , Virulência/genética
8.
FEMS Microbiol Lett ; 149(2): 273-8, 1997 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-9141669

RESUMO

The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although isoniazid has been used for the treatment of leprosy, it is shown here that the katG gene of Mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. Inactive genes were detected by the polymerase chain reaction in several isolates of M. leprae, of different geographical origins, and attempts to complement an isoniazid-resistant strain of Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias , Isoniazida/farmacologia , Hanseníase/microbiologia , Mycobacterium leprae/genética , Peroxidases/genética , Clonagem Molecular , Cosmídeos , Genes Bacterianos/genética , Hanseníase/tratamento farmacológico , Dados de Sequência Molecular , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/enzimologia , Pseudogenes/genética , Homologia de Sequência de Aminoácidos
9.
Clin Microbiol Rev ; 8(4): 496-514, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8665467

RESUMO

The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes. Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M. tuberculosis and many Mycobacterium leprae isolates. Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs). Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M. tuberculosis isolates. A majority of fluoroquinolone-resistant M. tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region. Multidrug-resistant isolates of M. tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents. Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance. These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory.


Assuntos
Anti-Infecciosos/farmacologia , Antibióticos Antituberculose/farmacologia , Genes Bacterianos/genética , Isoniazida/farmacologia , Mutação/genética , Mycobacterium/efeitos dos fármacos , Sequência de Aminoácidos , Sequência de Bases , Resistência Microbiana a Medicamentos/genética , Fluoroquinolonas , Dados de Sequência Molecular , Mycobacterium/genética
10.
Mol Microbiol ; 17(5): 889-900, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8596438

RESUMO

The systems participating in detoxification of reactive oxygen intermediates in Mycobacterium tuberculosis are believed to play a dual role in the biology of this highly adapted human pathogen: (i) they may contribute to the survival of this bacterium in the host; and (ii) alterations in the gene encoding catalase/peroxidase have been linked to this organism's resistance to the front-line antituberculosis drug isoniazid. These relationships prompted us to extend investigations of the oxidative-stress-response systems in M. tuberculosis by analysing the alkyl hydroperoxide reductase gene ahpC and its putative regulator oxyR. Surprisingly, the oxyR gene was found to be inactivated by multiple lesions in M. tuberculosis H37Rv. These alterations were observed in all M. tuberculosis strains tested, and in members of the M. tuberculosis complex: Mycobacterium bovis BCG, Mycobacterium africanum, and Mycobacterium microti. The corresponding region carrying these genes in Mycobacterium leprae, an organism not sensitive to isoniazid, has a complete oxyR gene divergently transcribed from ahpC. An increase in minimal inhibitory concentration for isoniazid was observed upon transformation of M. tuberculosis H37Rv with cosmids carrying the oxyR-ahpC region of M. leprae. In keeping with the observed inactivation of oxyR, transcriptional activity of the corresponding region in M. tuberculosis was an order of magnitude lower than that of the oxyR gene from M. leprae. While the loss of this putative regulator of oxidative-stress response in M. tuberculosis is paradoxical considering the fact that survival in host macrophages is regarded as a critical feature of this pathogen, it offers a partial explanation for the exquisite sensitivity of M. tuberculosis to isoniazid.


Assuntos
Proteínas de Ligação a DNA , Genes Bacterianos , Genes Reguladores , Isoniazida/farmacologia , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium/genética , Estresse Oxidativo/genética , Oxirredutases/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Sequência de Bases , Catalase/genética , Humanos , Dados de Sequência Molecular , Mycobacterium bovis/genética , Mycobacterium leprae/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/fisiologia , Oxirredutases/biossíntese , Peroxidases/genética , Peroxirredoxinas , Proteínas Repressoras/biossíntese , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/biossíntese
11.
Int J Lepr Other Mycobact Dis ; 59(2): 262-70, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2071984

RESUMO

Laser microprobe mass analysis of single bacterial organisms allows the determination of their intrabacterial ratio of sodium-to-potassium ions and the registration of fragment ions originating from their organic bacterial cell matrices as mass fingerprint spectra. It has been established previously that the intrabacterial cation ratio provides information on the physiological state of an individual bacterial cell. In the present experiments it is also shown, with different cultivable mycobacterial species and strains (drug sensitive and resistant) exposed to various drugs, that data derived from the evaluation of the mass fingerprint spectra reflect changes in the degree of impairment. The analysis of Mycobacterium leprae derived from a limited number of skin biopsies of lepromatous/borderline lepromatous leprosy patients under World Health Organization-recommended multiple-drug therapy (WHO/MDT) showed impairment of the organisms with both of the methods of measurement in proportion to the duration of treatment except in one case. In one M. leprae population from a patient who had been treated for 19 months, the fingerprint evaluation gave the first evidence for an insufficient response to treatment. This was further confirmed by the unusual frequency distribution of the Na+,K+ ratios which revealed the existence of two subpopulations, one impaired and one unimpaired.


Assuntos
Antibacterianos/farmacologia , Hansenostáticos/farmacologia , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium/efeitos dos fármacos , Potássio/análise , Sódio/análise , Resistência Microbiana a Medicamentos , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Dimorfa/microbiologia , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/microbiologia , Espectrometria de Massas , Mycobacterium/análise , Mycobacterium leprae/análise , Polimixina B/farmacologia , Polimixina B/uso terapêutico , Rifampina/farmacologia , Rifampina/uso terapêutico , Trimetoprima/farmacologia , Trimetoprima/uso terapêutico
13.
s.l; s.n; May-Jun. 1979. 7 p. tab.
Não convencional em Espanhol | SES-SP, HANSEN, SESSP-ILSLACERVO, SES-SP | ID: biblio-1240715

RESUMO

Se estudió un grupo de 86 enfermos tuberculosos que recebieron esquemas terapèuticos con Isoniacida y Rifampicina y se evaluó la acción de esas drogas sobre el hígado. Para ello, antes de iniciar la quimioterapia, se praticó una biopsia hepática y se dosaron transaminasas, fosfatasa y bilirrubina séricas; al finalizar el tercer mes de tratamiento se repitió una biopsia hepática. Los tests funcionales se repitieron mensualmente durante todo el tratamiento. El grupo I (10 casos) recibió Isonacida, Ethambutol y Estreptomicina. En la biopsia inicial hubo 1 caso con transformación grasa y 1 con necrosis focal; al 3er. mes persistía la necrosis focal en 1 caso y apreció en otros 3. El grupo II (14 casos) recibió Rifampicina, Ethambutol y Capreomicina.


Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Adolescente , Etambutol/uso terapêutico , Fígado/patologia , Isoniazida/administração & dosagem , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Quimioterapia Combinada , Rifampina/administração & dosagem , Rifampina/farmacologia , Rifampina/uso terapêutico
14.
Acta Leprol ; (73): 13-28, 1978.
Artigo em Inglês | MEDLINE | ID: mdl-108909

RESUMO

Drug sensitivity was tested using liquid medium on three stains isolated from the subcutaneous nodules of L-type patients who have long been administered DDS alone. The results revealed that the first strain was resistant to DDS up to the concentration of 1.0 microgram/ml suggesting as if it were DDS dependent or enhanced strain, whereas the second strain was completely sensitive to DDS even at the lowest concentration of 0.01 microgram/ml suggesting possible inactivation of this drug in the host patient. The third strain was completely resistant to 0.1 microgram/ml, but sensitive to 1.0 microgram/ml of DDS, suggesting that the therapeutic effect can not be expected any more, when the strain becomes resistant to 0.1 microgram/ml of DDS. All of the three strains were sensitive to REP at the concentration of 0.01 microgram/ml, and the host patients of the former two strains showed rapid improvement of the clinical symptomes after REP administration. That the second strain was sensitive to INH at the concentratin of 0.01 microgram/ml suggested the availability of the combined use of INH in the chemotherapy of leprosy.


Assuntos
Dapsona/farmacologia , Hanseníase/tratamento farmacológico , Mycobacterium leprae/efeitos dos fármacos , Dapsona/administração & dosagem , Dapsona/uso terapêutico , Resistência Microbiana a Medicamentos , Feminino , Humanos , Isoniazida/farmacologia , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Rifampina/farmacologia , Fatores de Tempo
17.
Microbios ; 19(76): 117-23, 1977.
Artigo em Inglês | MEDLINE | ID: mdl-366337

RESUMO

Sensitivity to anti-leprous drugs of M. leprae isolated from an L-type leprosy patient was tested using M--Y 14b liquid medium by direct and indirect methods. The results revealed that the strain, SR61-L74, was almost completely resistant to DDS, and responded only to the long-term administration of Streptomycin and Isoniazid. However, the strain was completely sensitive to rifampicin which had never been administered previously. The subsequent administration of rifampicin resulted in a rapid improvement of the patient's clinical symptoms. It can be concluded that the in vitro method, both direct and indirect, to test the sensitivity of M. leprae to anti-leprous drugs is economic, and accordingly available practically as one of the routine examinations in the laboratory of ordinary leprosaria. This must be very beneficial to the treatment of leprosy patients.


Assuntos
Hansenostáticos/farmacologia , Hanseníase/microbiologia , Mycobacterium leprae/efeitos dos fármacos , Dapsona/farmacologia , Resistência Microbiana a Medicamentos , Humanos , Isoniazida/farmacologia , Hanseníase/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Rifampina/farmacologia , Estreptomicina/farmacologia
20.
Int J Lepr Other Mycobact Dis ; 43(3): 234-8, 1975.
Artigo em Inglês | MEDLINE | ID: mdl-176120

RESUMO

A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M. lepraemurium. The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C. Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin. The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness. The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M. lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible. Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M. leprae in vitro.


Assuntos
Antibacterianos/farmacologia , Infecções por Mycobacterium/tratamento farmacológico , Mycobacterium lepraemurium/efeitos dos fármacos , Bacitracina/farmacologia , Cefaloridina/farmacologia , Cloranfenicol/farmacologia , Dactinomicina/farmacologia , Dapsona/farmacologia , Etionamida/farmacologia , Isoniazida/farmacologia , Canamicina/farmacologia , Metenamina/farmacologia , Testes de Sensibilidade Microbiana , Nitrofurantoína/farmacologia , Oxacilina/farmacologia , Polimixinas/farmacologia , Radiometria , Rifampina/farmacologia , Estreptomicina/farmacologia , Sulfadimetoxina/farmacologia , Vancomicina/farmacologia
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