rifampin and lomefloxacin

Combined antituberculosis substances induced a dose-dependent changes in activity of dehydrogenases and hydrolases in rat lymphocytes. The main toxic effect of the substances was related to inhibition of mitochondrial dehydrogenases (succinate dehydrogenase and α-glycerol phosphate dehydrogenase) usually followed by suppression of activity of hydrolytic enzymes (acid phosphatase and non-specific esterase). Opposite changes in lactate dehydrogenase activity reflected specific features of intoxication.

Topics: Acid Phosphatase; Administration, Oral; Animals; Animals, Outbred Strains; Antitubercular Agents; Drug Combinations; Esterases; Ethambutol; Fluoroquinolones; Gene Expression; Glycerolphosphate Dehydrogenase; Isoniazid; L-Lactate Dehydrogenase; Lymphocytes; Male; Primary Cell Culture; Prothionamide; Pyrazinamide; Rats; Rifampin; Succinate Dehydrogenase

Topics: Adult; Anti-Infective Agents; Antitubercular Agents; Fluoroquinolones; Humans; Isoniazid; Middle Aged; Quinolones; Respiratory Tract Infections; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

The peculiarities of the mechanism of the lomefloxacin bactericidal action on Mycobacterium tuberculosis were studied. The electron microscopy of ultrathin sections of the cells of M.tuberculosis H37Rv exposed to 10 micrograms/ml of lomefloxacin for 24 hours revealed severe changes in their ultrastructure: exfoliation of the cell wall from the cytoplasmic membrane, loosening and fragmentation of the cytoplasmic membrane, lowering of the cytoplasm thickness, vacuolization and twisting of the mesosomes. The exposure of the cells to lomefloxacin for 72 hours resulted in their complete destruction: the cells proved to be a mass of unidentifiable fragments. Some destructions such as exfoliation of the intracytoplasmic membrane and the cytoplasm loosening and vacuolization were observed in the tubercle bacilli localized inside the phagosomes of the murine lung macrophages exposed to lomefloxacin. Such destructions were evident of the antibiotic good penetration not only into the macrophages but also through the phagosome walls as well as of the lomefloxacin intracellular bactericidal activity. In the experiments with the culture of the lung tissue from the tuberculosis foci of mice the basic mechanism fo the lomefloxacin action on M.tuberculosis was demonstrated: the lomefloxacin bactericidal effect was realized through the pathway of mechanism A of the antimicrobial action of fluoroquinolones.

Topics: Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Cell Wall; Colony Count, Microbial; Cytoplasm; Drug Antagonism; Fluoroquinolones; Macrophages, Alveolar; Mice; Microscopy, Electron; Mycobacterium tuberculosis; Quinolones; Rifampin