rifamycin-sv and Tuberculosis

A new rifamycin derivative 3-(4-cinnamyl-piperazinyl iminomethyl) rifamycin SV (T9) and its sodium salt (T11, Rifacinna((R))) were in vitro, in vivo, toxicologically and clinically investigated in comparison with rifampicin, rifapentine, rifabutin, rifalazil. Our experiments showed that Rifacinna exhibits excellent in vitro activity against Gram(+), Gram (-) aerobic, anaerobic pathogens and mycobacteria. Rifacinna is active against Staphylococcus, Streptococcus spp. including MRSA, with MIC90- 0.06-0.5 mg/L; against Gram(+), Gram (-) anaerobes with MIC90 0.5 - 1 mg/L; against Mycobacterium tuberculosis (MTB) with MIC90 0.062 mg/L; against MDR resistant MTB (25%-30 %) and Mycobacterium avium complex (MAC) strains with MICs 0.6-1.0 mg/L. It shows high intraphagocytic activity against MAC strains (0.06 0.125mg/L). Single daily dose 10 mg/kg provides complete erradication of mycobacteria in experimental generalized tuberculosis. Pharmacological studies established: excellent pharmacokinetic profile following single oral dose 10mg/kg Tmax 5-6 h, C(max) 5-9 mg/L, T1/2 33-34 h; low toxicity; no teratogenic and embryotoxic effects. The clinical study of Rifacinna shows higher therapeutic efficacy than Rifampicin in patients with infiltrative, disseminated and cavitary form of pulmonary tuberculosis, good tolerability and safety profile. Some of the recent patents related to the treatment of tuberculosis are discussed in this review article.

Topics: Animals; Antibiotics, Antitubercular; Disease Models, Animal; Humans; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium; Rifamycins; Structure-Activity Relationship; Toxicity Tests; Treatment Outcome; Tuberculosis

Rifampicin is active against both intracellular and extracellular Mycobacterium tuberculosis. The ability to measure rifampicin drug concentrations in both plasma and in cells may be useful in evaluating the suitability of dosage regimens for populations and individuals. Here a novel simple, precise and accurate method for the quantification of rifampicin in both cells and plasma is reported. Sample proteins were precipitated with acetonitrile containing the internal standard and then diluted with water. Aliquots of supernatant were then injected into the HPLC-MS system for chromatographic separation and detection. Rifampicin calibration curves encompassed concentrations from 100 to 12,800 ng/mL. Intra- and inter-assay precision and accuracy were determined using low, medium and high concentration quality control samples and was found to be within 10% in all cases. Rifampicin concentrations were found to be unaffected by freeze-thaw cycles, but were significantly affected by heat-inactivation (58 degrees C, 40 min). This assay was successfully utilised to determine the pharmacokinetic profile of rifampicin in plasma and peripheral blood mononuclear cells (PBMC) in 8 tuberculosis patients receiving rifampicin over an 8h period.

Topics: Administration, Oral; Antitubercular Agents; Calibration; Chromatography, High Pressure Liquid; Drug Stability; Female; Humans; Leukocytes, Mononuclear; Male; Mass Spectrometry; Reference Standards; Reproducibility of Results; Rifampin; Rifamycins; Sensitivity and Specificity; Tuberculosis

We sought to determine the risk of acquired rifamycin resistant (ARR) tuberculosis associated with rifampin- versus rifabutin-based directly observed therapy and to assess the risk factors for relapse of tuberculosis. This observational cohort study included patients with culture-confirmed rifamycin-susceptible tuberculosis reported to the Baltimore City Health Department (Baltimore, MD) during the period of January 1993 through December 2001. Of the 407 patients, 108 (27%) were human immunodeficiency virus (HIV) seropositive, 161 (40%) were HIV seronegative, and 138 (34%) had an unknown serostatus. Three (2.8%) of 108 HIV-seropositive persons had ARR tuberculosis, compared with 0 of 299 persons with negative or unknown HIV serostatus (P=.02). Among HIV-seropositive patients, 3 (3.7%) of 81 who were treated with rifampin and 0 of 27 who were treated with rifabutin had ARR tuberculosis (P=.57). Among HIV-seropositive patients, the only risk factor for recurrent tuberculosis was a low median initial CD4+ T lymphocyte count (51 vs. 138 cells/mm3; P=.02). The median CD4+ T lymphocyte count among patients with ARR tuberculosis was 51 cells/mm3. ARR tuberculosis can occur with rifampin-based regimens, but in this study, the risk was not significantly higher than that for a rifabutin-based regimen.

Topics: Adult; Aged; Antitubercular Agents; Drug Resistance, Bacterial; Female; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Male; Middle Aged; Recurrence; Rifabutin; Rifamycins; Risk Factors; Serologic Tests; Tuberculosis

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Pneumonectomy; Rifamycins; Staphylococcal Infections; Surgical Wound Infection; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pleural; Tuberculosis, Pulmonary

Topics: Animals; Biomedical Research; Guinea Pigs; Hypersensitivity; Isoniazid; Pharmacology; Research; Rifamycins; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary

Topics: Bronchial Fistula; Drug Resistance; Drug Resistance, Microbial; Empyema; Empyema, Tuberculous; Pharmacology; Rifamycins; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Bronchial Fistula; Empyema; Empyema, Tuberculous; Humans; Rifamycins; Tuberculosis

Topics: Acetates; Carbon Isotopes; DNA; DNA, Bacterial; Metabolism; Mycobacterium tuberculosis; Pharmacology; Phosphates; Phosphorus Isotopes; Proteins; Research; Rifamycins; RNA; RNA, Bacterial; Sulfates; Sulfur Isotopes; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Blood Glucose; Carbohydrate Metabolism; Cycloserine; Diabetes Mellitus; Drug Tolerance; Ethionamide; Humans; Isoniazid; Kanamycin; Pharmacology; Pyrazinamide; Rifamycins; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Drug Therapy; Humans; Infusions, Parenteral; Isoniazid; Radiography, Thoracic; Rifamycins; Streptomycin; Tomography; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Drug Therapy; Drug Tolerance; Infusions, Parenteral; Povidone; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis

Topics: Rifamycins; Tuberculosis

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Guinea Pigs; Rifamycins; Skin; Tuberculosis

Topics: Antitubercular Agents; Mycobacterium tuberculosis; Rifamycins; Tuberculosis

Topics: Caves; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Empyema; Empyema, Tuberculous; Rifamycins; Tuberculosis

Topics: Drug Tolerance; Infusions, Parenteral; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis

Topics: Female; Humans; Rifamycins; Tuberculosis; Tuberculosis, Female Genital; Urogenital System

Topics: Humans; Lymph Nodes; Rifamycins; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Osteoarticular

Topics: Animals; Antitubercular Agents; Mice; Mycobacterium tuberculosis; Rifamycins; Tuberculosis

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Rifamycins; Tuberculosis

Topics: Antitubercular Agents; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Urogenital; Urinary Tract; Urogenital System

Topics: Bronchiectasis; Bronchitis; Lung Abscess; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Chemical Phenomena; Chemistry; Dermatology; Metabolism; Pharmacology; Rifamycins; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Guinea Pigs; Pharmacology; Research; Rifamycins; Tuberculosis

Topics: Drug Tolerance; Guinea Pigs; Metabolism; Mycobacterium tuberculosis; Pharmacology; Research; Rifamycins; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Glycoside Hydrolases; Hyaluronoglucosaminidase; Rifamycins; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Bronchial Fistula; Drug Resistance; Drug Resistance, Microbial; Empyema; Empyema, Tuberculous; Pharmacology; Rifamycins; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary; Veins

Topics: Rifamycins; Tuberculosis; Tuberculosis, Pulmonary

Topics: Female; Humans; Rifamycins; Tuberculosis; Tuberculosis, Female Genital

Topics: Anti-Bacterial Agents; Rifamycins; Tuberculosis; Tuberculosis, Pulmonary