title: Early bactericidal activity of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater) in patients with pulmonary tuberculosis.
abstract: The early bactericidal activity (EBA) of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater: Mer National) was evaluated in patients with pulmonary tuberculosis who were sputum-positive on microscopy for acid-fast bacilli. Twenty-eight patients (mean age 33 years and weight 51 kg on average; range 40-59 kg) were studied. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days following the start of treatment was estimated from counts of colony-forming units (CFUs) of M. tuberculosis per ml of sputum cultured on selective 7H10 agar medium. The EBA for ethambutol determined in 9 patients was 0.245 +/- 0.046, log10 CFU/ml sputum/day, that for pyrazinamide was 0.003 +/- 0.014 log10 CFU/ml sputum/day and that for Rifater 0.558 +/- 0.054 log10 CFU/ml sputum/day. The results obtained are similar to those reported in a previous study of the first 2 days of treatment, but in smaller numbers of patients, and confirm the moderate EBA of ethambutol while pyrazinamide is again shown to have very little EBA. Rifater has a marked EBA which may be due mainly to the action of isoniazid. This methodology may be valuable in the rapid evaluation of the bactericidal activity of new antituberculosis agents and the comparison of different dose sizes of agents of the same class.
authors.affiliation: Department of Pharmacology, Tygerberg Hospital, W. Cape.
authors.forename: F J
authors.initials: FJ
authors.lastname: Botha
authors.forename: F A
authors.initials: FA
authors.lastname: Sirgel
authors.forename: D P
authors.initials: DP
authors.lastname: Parkin
authors.forename: B W
authors.initials: BW
authors.lastname: van de Wal
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.forename: D A
authors.initials: DA
authors.lastname: Mitchison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; C087181:isoniazid, pyrazinamide, rifampin drug combination; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin