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)

CGI 17341 (2-ethyl-5-nitro-2,3-dihydro[2-1b]imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents. At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis. CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol. While the in vitro activity of CGI 17341 against M. tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721. The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed. In mice infected with M. tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection. CGI 17341 gave a dose-dependent (r = 0.995) and significant increase in the survival time. Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities. Further investigations on this compound are warranted.
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PMID:In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis. 845 46

The ability of human monocytes to phagocytize and respond to infection by Mycobacterium fortuitum was tested using the method of Crowle and May. The monocytes were obtained from heparinized donor blood samples and separated from lymphocytes by adherence to plastic surfaces. M. fortuitum infection was performed immediately. Intracellular viability was indicated by colony forming units (CFU) done at 2 hour intervals. Monocytes were found to cause a rapid reduction in CFU during the first 2 hours of incubation. The rate of killing of M. fortuitum decreased thereafter but continued for the entire 8-hour study period. In parallel tests, ciprofloxacin and ofloxacin were added to the culture medium. Increased intracellular killing was observed with drug concentrations above 2 x MIC in both cases. Ofloxacin showed better antimycobacterial effects than ciprofloxacin.
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PMID:Control of intracellular growth of Mycobacterium fortuitum by human monocytes in vitro. 851 90

Mycobacterium avium infection is a frequent complication during the late stage of AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are bactericidal against M. avium, and their use has dramatically improved the prognosis of this infection. In vitro, azithromycin has MICs against M. avium ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low concentrations in serum, close to 0.4 mg/l, very high intracellular concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is active in vitro in the model of macrophage infection. Furthermore, azithromycin is active against murine experimental infection with M. avium. Clinical studies conducted among patients with AIDS have shown that azithromycin was active against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies are designed to better determine the ideal dose, to compare its activity with that of clarithromycin and to determine the antibiotics that could be combined to prevent the selection of resistant mutants. Other ongoing studies are evaluating the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.
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PMID:[Azithromycin and Mycobacterium avium infection]. 853 84

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.
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PMID:In vitro activity of levofloxacin, singly and in combination with rifamycin analogs, against Mycobacterium leprae. 854 Jul 26

During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpholine moiety. The rational design, synthesis, and evaluation of the in vitro antimycobacterial activity of these analogues is described. Potent activity against a screening strain of Mycobacterium tuberculosis was demonstrated by 6 and 7 (minimum inhibitory concentrations or MIC's < or = 0.125 micrograms/mL). Oxazolidinones 6 and 8 exhibit MIC90 values of 0.50 micrograms/mL or less against a panel of organisms consisting of five drug-sensitive and five multidrug-resistant strains of M. tuberculosis, with 6 being the most active congener. Potent in vitro activity against other mycobacterial species was also demonstrated by 6. For example, 6 exhibited excellent in vitro activity against multiple clinical isolates of Mycobacterium avium complex (MIC's = 0.5-4 micrograms/mL). Orally administered 6 displays in vivo efficacy against M. tuberculosis and M. avium similar to that of clinical comparators isoniazid and azithromycin, respectively. Consideration of these factors, along with a favorable pharmaco-kinetic and chronic toxicity profile in rats, suggests that 6 (U-100480) is a promising antimycobacterial agent.
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PMID:Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. 857 10

The in vitro and in vivo activities of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium tuberculosis were studied. The MIC at which 50% of the isolates are inhibited (MIC50) and the MIC90 of KRM for 30 fresh isolates of M. tuberculosis measured by the BACTEC 460 TB System were 0.016 and 2 micrograms/ml, respectively. These values were much lower than those for rifampin (RMP), which were 4 and >128 micrograms/ml, respectively, and considerably lower than those for rifabutin (RBT), which were 0.125 and 8 micrograms/ml, respectively. A correlational analysis of the MICs of these drugs for the clinical isolates revealed the presence of cross-resistance of the organisms to KRM and either RMP or RBT although the MICs of KRM were distributed over a much lower range than were those of the other two drugs. KRM and RMP at concentrations of 1 to 10 micrograms/ml almost completely inhibited the bacterial growth of RMP-sensitive strains (H37Rv, Kurono, and Fujii) of M. tuberculosis phagocytosed in macrophage-derived J774.1 cells. KRM was more active than RMP in inhibiting the growth of the RMP-resistant (MIC = 8 micrograms/ml) Kurata strain but failed to show such an effect against the RMP-resistant (MIC >128 micrograms/ml) Watanabe stain. When KRM was given to M. tuberculosis-infected mice at dosages of 5 to 20 mg/kg of body weight by gavage, one daily six times per week from day 1 after infection, it was much more efficacious than RMP against infections induced in mice by the RMP-sensitive Kurono strain, as measured by a reduction of rates of mortality, a reduction of the frequency and extent of gross lung lesions, histopathological changes in lung tissues, and a decrease in the bacterial loads in the lungs and spleens of infected mice. KRM also displayed significant therapeutic efficacy against infection induced by the RMP-resistant Kurata strain, while neither KRM nor RMP was efficacious against infection by the RMP-resistant Watanabe strain. In the case of infection with the Kurono strain, the efficacy of the drugs in prolonging the time of survival was in the order KRM, RBT, RMP. KRM was much more efficacious than RMP, when given at 1- to 4-week intervals. These findings suggest that KRM may be useful for the clinical treatment of tuberculosis contracted through RMP-sensitive strains, even when it is administered at long intervals.
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PMID:In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis. 861 85

The antimycobacterial activities of a new rifampin (RIF) derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (To), against 20 susceptible and multidrug-resistant strains of Mycobacterium tuberculosis and 20 Mycobacterium avium complex (MAC) strains were investigated. The radiometric MICs of T9 for M. tuberculosis were significantly lower than those of RIF. The MICs of T9 and RIF at which 90% of the RIF-susceptible strains were inhibited were < or = 0.25 and < or = 0.5 micrograms/ml, respectively. Interestingly, T9 had lower MICs against some RIF-resistant M. tuberculosis strains. T9 had better activity against MAC strains, and the MIC at which 90% of the MAC strains were inhibited was < or = 0.125 micrograms/ml, and that of RIF was < or = 2.0 micrograms/ml. T9 also showed high in vitro bactericidal and intracellular activities which were significantly superior to those of RIF against both M. tuberculosis, and MAC strains. More importantly, T9 showed excellent in vivo activity against M. tuberculosis H37Rv compared with that of RIF in both the lungs and spleens of C57BL/6 mice, indicating the potential therapeutic value of T9 in the treatment of mycobacterial infections.
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PMID:Antimycobacterial activity of a new rifamycin derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (T9). 861 89

Etest (AB BIODISK, Solna, Sweden) is a precise MIC method and the practical method of choice for the susceptibility testing of many fastidious organisms, including rapidly growing mycobacteria. Methods recommended by the National Committee for Clinical Laboratory Standards for the susceptibility testing of Mycobacterium tuberculosis include the Bactec (Becton Dickinson, Sparks, Md.) broth and agar proportion methods. A comparison of Etest with the Bactec broth method for testing the susceptibility of M. tuberculosis to four first-line antituberculous agents demonstrated equivalent interpretive results for 100% of the isolates tested. Agreements with agar proportion MICs, within +/-2 log2 dilutions, were 90, 93, 100, and 94% for ethambutol, isoniazid, rifampin, and streptomycin, respectively. Etest MICs were easily read within 5 to 10 days of inoculation. Preparation of the inoculum with a turbidity equivalent to a McFarland 3.0 standard prepared from growth on an agar surface and with a broth with a Bactec growth index of > 999 yielded equivalent results. Clinical isolates for which the MICs were reproducible were also identified as possible quality control strains. The Etest method appears to be an alternative method for testing the susceptibility of M. tuberculosis isolates to the four most commonly used therapeutic agents.
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PMID:Testing of Mycobacterium tuberculosis susceptibility to ethambutol, isoniazid, rifampin, and streptomycin by using Etest. 878 67

The activity of pyrazinamide (PZA) against eight isolates of Mycobacterium tuberculosis in a murine infection model was evaluated. M. tuberculosis isolates with various degrees of in vitro susceptibility to PZA (MIC range, 32 to > 2,048 micrograms/ml) were used. Four-week-old female mice were infected intravenously with approximately 10(7) viable M. tuberculosis organisms. PZA at 150 mg/kg of body weight was started 1 day postinfection and given 5 days/week for 4 weeks. Infected but untreated mice were compared with PZA-treated mice. Mice were sacrificed at the completion of the treatment period, and viable cell counts were determined from homogenates of spleens and right lungs. PZA had activity in the murine test system against M. tuberculosis isolates for which the MICs were < or = 256 micrograms/ml. However, there was an inconsistent correlation between the absolute MICs and the reductions in organ viable cell counts. Studies with drug-resistant M. tuberculosis isolates with an isogenic background would improve evaluation of drug efficacy in the murine test system. Further evaluation of antimycobacterial agents against monodrug-resistant isolates will provide data that will be useful for development of algorithms for treatment of infection with drug-resistant organisms.
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PMID:Activity of pyrazinamide in a murine model against Mycobacterium tuberculosis isolates with various levels of in vitro susceptibility. 878 71

By using the radiometric BACTEC 460-TB methodology, the inhibitory and bactericidal activity of the optically active L-isomer of ofloxacin (levofloxacin) was compared with those of the D-isomer and the commercially available mixture containing equal amounts of DL-isomers (ofloxacin) against the Mycobacterium tuberculosis complex (type strain H37Rv, a panel of drug-susceptible and -resistant clinical isolates including multidrug-resistant isolates of M. tuberculosis, as well as M. africanum, M. bovis, and M. bovis BCG). Levofloxacin MICs (range 0.50 to 0.75 microgram/ml) were about 1 dilution lower than those of ofloxacin (MIC range, 0.75 to 1.00 microgram/ml) and 5 to 6 dilutions lower than those of the D-isomer (MIC range, 32 to 60 micrograms/ml). The MICs of levofloxacin, ofloxacin, and D-ofloxacin at which 90% of the strains are inhibited were 0.50, 1.00, and 64 micrograms/ml, respectively. The multidrug-resistant M. tuberculosis strains resistant to first-line drugs were as susceptible to quinolones as the wild-type drug-susceptible isolates. Levofloxacin at 0.5 microgram/ml showed bactericidal activity comparable to the activities of 1.0 microgram of ofloxacin per ml and 64 micrograms of D-ofloxacin per ml, with MBCs within the range of 0.5 to 2.0 micrograms/ml, compared with MBCs of 0.75 to 4.0 micrograms of ofloxacin per ml for M. tuberculosis, M. africanum, M. bovis BCG. Combination testing of sub-MICs of levolofoxacin with other first-line (isoniazid, rifampin, and ethambutol) and second-line (amikacin and clofazimine) antituberculous drugs was evaluated with various two-, three-, and four-drug combinations; enhanced drug activity was observed in 8 of 25, 12 of 20, and 8 of 15 tests, respectively, indicating that levofloxacin acts in synergy with other antituberculous drugs.
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PMID:In vitro activities of levofloxacin used alone and in combination with first- and second-line antituberculous drugs against Mycobacterium tuberculosis. 880 49


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