rifapentine and Mycobacterium-avium-intracellulare-Infection

Topics: Antibiotics, Antitubercular; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Studies have shown clarithromycin (Biaxin) and rifabutin to be effective against Mycobacterium avium complex (MAC), and to improve survivability. Abbott Laboratories is seeking approval from the Food and Drug Administration (FDA) for clarithromycin use in preventing MAC. Marion Merrell Dow, the manufacturer of rifabutin, is planning a prophylaxis trial with a close cousin of the drug, rifapentine. Rifapentine has a long half-life, and has the potential to lengthen intermittent treatment for tuberculosis. It is believed that this long half-life may mean it can maintain a higher blood level and thereby maintain better effectiveness than rifabutin against fast-growing MAC organisms.

Topics: AIDS-Related Opportunistic Infections; Animals; Antitubercular Agents; CD4 Lymphocyte Count; Clarithromycin; Half-Life; Humans; Mycobacterium avium-intracellulare Infection; Placebos; Randomized Controlled Trials as Topic; Rifabutin; Rifampin

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Clinical Trials as Topic; Drug Approval; Drug Industry; Fluoroquinolones; Humans; Mycobacterium avium-intracellulare Infection; Rifampin; Technology, Pharmaceutical; Tuberculosis, Multidrug-Resistant; United States

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.

Topics: Animals; Antitubercular Agents; Azithromycin; Cyclosporine; Erythromycin; Male; Mycobacterium avium-intracellulare Infection; Rats; Rats, Sprague-Dawley; Rifabutin; Rifampin; Rifamycins; Tissue Distribution

The comparative activities of newer rifamycin analogs and the activity of rifabutin or rifapentine in combination with other antimycobacterial agents was evaluated in the beige (C57BL/6J; bgj/bgj) mouse model of disseminated Mycobacterium avium infection. Rifabutin and rifapentine at 20 mg/kg of body weight had comparable activities. P/DEA and CGP 7040 at 20 mg/kg were less active. The combination of ethambutol at 125 mg/kg and rifabutin at 20 mg/kg resulted in a slight increase in activity beyond that seen with rifabutin alone against organisms in the spleens. The combination of ethambutol and rifapentine at 20 mg/kg resulted in a modest increase in activity beyond that seen with rifapentine alone against organisms in the lungs. The combination of ethionamide at 125 mg/kg and rifapentine resulted in a decrease in activity compared with that for rifapentine alone. The combination of clofazimine at 20 mg/kg and rifapentine resulted in increased activity in the mouse model. The combination of clofazimine and rifapentine (or rifabutin) appears to be an attractive regimen that should be evaluated for the treatment of human infections due to M. avium complex.

Topics: Animals; Culture Media; Drug Therapy, Combination; Female; Male; Mice; Mice, Inbred C57BL; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Rifamycins