Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-one strains of 15 species of rapidly growing mycobacteria were studied for their susceptibilities to fatty acids with 2 to 20 carbons by the agar dilution method at pH 7.0. Most mycobacteria other than potential pathogens (Mycobacterium fortuitum and Mycobacterium chelonei) were resistant to saturated fatty acids, except for lauric acid (C12:0) (MIC, 6.25 to 25 micrograms/ml) and capric acid (C10:0) (MIC, 50 to 100 micrograms#ml). M. fortuitum and M. chelonei were substantially insusceptible to these fatty acids. Unsaturated fatty acids with 16 to 20 carbons, except for C20:5, were highly toxic to group IV mycobacteria other than M. fortuitum, M. chelonei, Mycobacterium smegmatis, and Mycobacterium phlei, these being highly resistant to all the unsaturated acids, except for C16:1, C18:3, and C20:5. Introduction of double bonds to C16 to C20 fatty acids caused a marked increase in their activities that depended on the increase in the number of double bonds, at least up to three or four. M. fortuitum and M. chelonei were more resistant to the unsaturated fatty acids (particularly to C20:3 and C20:4) than the other group IV mycobacteria.
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PMID:Growth of group IV mycobacteria on medium containing various saturated and unsaturated fatty acids. 648 60

In an attempt to select a group of rapidly growing Mycobacteria which could serve as a model for the in vitro screening of rifamycin derivatives for their activity against Mycobacterium leprae, the MIC values of 237 strains of rapidly growing Mycobacteria were determined for 4 reference rifamycins with known activity against M. leprae and 19 rifamycins with unknown activity against M. leprae. Study of the results by a multivariate statistical technique, the principal components analysis, defined a group of 16 rapidly growing Mycobacteria (7 strains of M. phlei, 4 strains of M. thermoresistible, 3 strains of M. fortuitum and 2 strains of M. vaccae) showing the lowest distance to M. leprae. The analysis detected among rifamycin derivatives with different activities M. tuberculosis, compounds which should be active against M. leprae, and allows the selection of a limited number of rifamycins for the in vivo screening in the mouse model.
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PMID:Multivariate analysis of the activity of rifamycins against rapidly growing Mycobacteria, to define an in vitro screening model for their activity against mycobacterium leprae. 701 30

Neither amoxicillin nor clavulanic acid used alone was active at the highest level tested, i.e., 256.0 micrograms/ml, in vitro against 24 isolates of Mycobacterium fortuitum, Mycobacterium kansasii, and Mycobacterium marinum. However, the MIC of an amoxicillin-clavulanic acid combination of 2:1 was < or = 8.0/4.0 micrograms/ml for 50 percent of the isolates tested, with all isolates being inhibited in the range of 4.0/2.0 to 32.0/16.0 micrograms/ml, respectively. Titration of amoxicillin-clavulanic acid with a fixed 2-micrograms/ml concentration of ethambutol resulted in synergistic activity against 3 of 9 isolates of M. fortuitum, 10 of 10 isolates of M. kansasii, and 5 of 5 isolates of M. marinum. This observation was confirmed in a checkerboard analysis in which fractional inhibitory concentrations were < or = 0.5 for 20 of the 24 isolates. Synergistic activity was observed against the other four isolates in one of two trials. On the other hand, titration of amoxicillin-clavulanic acid in the presence of either one or two fixed concentrations of isoniazid, rifampin, cycloserine, tetracycline, or amikacin failed to result in synergism.
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PMID:Susceptibilities of nontuberculosis mycobacterial species to amoxicillin-clavulanic acid alone and in combination with antimycobacterial agents. 749 84

A colorimetric method for quantitative measurement of the susceptibility of Mycobacterium tuberculosis to antimicrobial agents is described. The method utilizes an oxidation-reduction dye, Alamar blue, as an indicator of growth. By this method, MICs of isoniazid, rifampin, streptomycin, and ethambutol were determined for 50 strains of M. tuberculosis. Colorimetric MIC results were available on the 7th, 10th, or 14th day of incubation for 29 (58%), 14 (28%), and 7 (14%) of the 50 strains, respectively. When MIC susceptibility results were compared with results obtained by the agar proportion method, increased levels of resistance detected by agar proportion were associated with higher MICs obtained by the colorimetric method. Tentative interpretive criteria for colorimetric MIC results which showed good agreement with results obtained by the agar proportion method were established. Interpretive agreement between the two methods was 98% for isoniazid, rifampin, and ethambutol and 94% for streptomycin. Overall, there was agreement between the two methods for 194 of 200 test results (97%). The colorimetric method is a rapid, quantitative, nonradiometric method for determining the antimicrobial susceptibility of M. tuberculosis.
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PMID:Colorimetric method for determining MICs of antimicrobial agents for Mycobacterium tuberculosis. 749 21

In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX.
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PMID:In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis. 757 27

The activities of four newly synthesized benzoxazinorifamycin derivatives, either alone or in combination with ofloxacin, against strains of Mycobacterium leprae were determined by assessing their effects on two biochemical parameters of metabolic activity which served as surrogate markers for growth in vitro. KRM-1648 and KRM-2312 were the most active agents tested against both a rifampicin-susceptible isolate (MICs of 0.05 and 0.1 mg/L respectively) and a rifampicin-resistant isolate (MICs of 0.2 and 0.3 mg/L respectively); both compounds were more active than either rifampicin or rifabutin. The activities of the two other derivatives, KRM-1657 and KRM-1668, against a rifampicin- susceptible strain (MICs of 0.3 mg/L) were similar to that of rifampicin, while the MIC of each of these agents for the rifampicin-resistant strain was 1.0mg/L. In common with rifabutin, both of the more active derivatives demonstrated synergy with ofloxacin against the rifampicin-susceptible isolates. The results of this study suggest that these compounds, in combination with ofloxacin as part of multidrug regimens, warrant further evaluation as treatment for patients with leprosy.
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PMID:The in-vitro activities of novel benzoxazinorifamycins against Mycobacterium leprae. 762 81

In vitro susceptibility of Mycobacterium leprae to two bipyridyl analogs was studied by using two biochemical parameters to measure the metabolic activity of the organism. VUF-8514 at 0.16 micrograms/ml, but not VUF-8842, completely inhibited the metabolic activity of M. leprae, and the action was bactericidal. When compared to rifampin (MIC 0.3 micrograms/ml), VUF-8514 was equally bactericidal against M. leprae.
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PMID:In vitro activities of 2,2'-bipyridyl analogs against Mycobacterium leprae. 769 82

We evaluated the in vitro antimicrobial activity of T-3761 and ofloxacin against representative pathogenic mycobacteria by the agar dilution method, using 7H11 agar medium. T-3761 showed appreciable antimicrobial activity against Mycobacterium tuberculosis (MIC90: 3.13 micrograms/ml), M. kansasii (MIC90: 6.25 micrograms/ml) and M. fortuitum (MIC90: 3.13 micrograms/ml), whereas the agent was not active against M. marinum (MIC90: 25 micrograms/ml), M. scrofulaceum (MIC90: 50 micrograms/ml), M. avium (MIC90: > 100 micrograms/ml), M. intracellulare (MIC90: > 100 micrograms/ml), M. chelonae subsp. abscessus (MIC90: > 100 micrograms/ml) and M. chelonae subsp. chelonae (MIC90: 50 micrograms/ml). The in vitro antimicrobial activity of T-3761 against M. fortuitum was a little more potent than that of ofloxacin, whereas the activity of T-3761 against the other mycobacteria was slightly inferior to that of ofloxacin. The antimycobacterial activity of T-3761 against M. tuberculosis H37Rv (MIC in vitro: T-3761 = 3.13 micrograms/ml, OFLX = 0.78 micrograms/ml) phagocytosed in murine peritoneal macrophages was less active than that of ofloxacin, when the macrophages were cultured in RPMI-1640 medium containing 1 microgram/ml or 10 micrograms/ml of these agents for up to 5 days. The activity of 10 micrograms/ml of T-3761 was equivalent to that of 1 microgram/ml of ofloxacin.
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PMID:[In vitro antimycobacterial activity of a new quinolone, T-3761]. 769 82

We investigated the activity of benzoxazinorifamycin (KRM-1648) against several drug-susceptible and multidrug-resistant strains of tubercle bacilli. Since KRM-1648 is a rifamycin derivative, we included some strains of Mycobacterium tuberculosis resistant to rifampin (RIF) among the multidrug-resistant strains. For RIF-susceptible strains, the MIC of KRM-1648 was much lower than that of RIF (MICs of KRM-1648 and RIF at which 90% of strains are inhibited, < or = 0.015 and < or = 0.25 micrograms/ml, respectively). The MBC of KRM-1648 (range, 0.007 to 0.03 microgram/ml) was also much lower than that of RIF (range, 0.5 to 1.0 microgram/ml). Postantibiotic effect studies with KRM-1648 showed a rapid reduction in the CFU counts with an exposure of 24 h or more, and its sterilizing effect was maintained even up to 21 days thereafter. Parallel postantibiotic effect studies with RIF showed a less significant effect with a faster recovery of growth, and RIF failed to sterilize the organisms even after 72 h of exposure. KRM-1648 at 0.125 and 0.25 microgram/ml caused complete inhibition of intracellular growth of M. tuberculosis in J774 A.1 macrophages after 48 h of exposure. After a similar exposure time RIF at a concentration of 0.25 microgram/ml caused complete inhibition of growth, but a concentration of 0.125 microgram/ml caused only a 50% reduction in growth compared with that of controls at day 7. With 24 h of pulsed exposure of the intracellular organisms to 0.25 micrograms of the drugs per ml, KRM-1648 caused complete inhibition of intracellular growth, while RIF caused only moderate inhibition of intracellular growth. These findings suggest that KRM-1648 is a potentially useful drug for the treatment of tuberculosis.
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PMID:In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli. 772 12

Strategies to augment conventional methods of drug delivery in treatment of multiple drug resistant tuberculosis are needed to achieve optimum results with available drugs. We have studied the effect of sub-minimum inhibitory concentrations (sub-MIC) of ethambutol and dimethyl sulphoxide on drug susceptibility of Mycobacterium tuberculosis strains both in vitro and in macrophages. At sub-MIC ethambutol between caused four and 64 fold increase in susceptibility to isoniazid rifampicin and streptomycin in four M. tuberculosis strains, resistant to these drugs. Incubation of the organisms with isoniazid and sub-MIC of dimethyl sulphoxide (2.5%) resulted in an eight-fold increase in susceptibility to the drug. Previous exposure of the organisms to sub-MIC of dimethyl sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC of sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC enhanced the activity of the anti-tuberculosis drugs against multiple drug resistant M. tuberculosis strains growing inside macrophages. Our data indicate that the agents which modify cell wall permeability can enhance the susceptibility of multiple drug resistant strains to drugs to which they were originally resistant. This could provide a new approach to treating drug resistant tuberculosis.
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PMID:Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide. 778 54


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