The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis

Previously untreated patients with smear-positive pulmonary tuberculosis were randomly allocated to treatment with 600, 300, 150 or 75 mg doses of rifabutin (LM427, ansamycin), 600, 300 or 150 mg of rifampicin, 300 mg isoniazid or to no drug daily for 2 days. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days, termed the early bactericidal activity (EBA), was estimated from counts of colony-forming units (cfu) on selective 7H-11 agar medium. The EBA for rifabutin ranged from −0.039 (an increase in counts) to 0.049 log 10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log 10 cfu/ml/day for 600 mg rifampicin and was 0.43 log 10 cfu/ml/day for 300 mg isoniazid. The difference between the EBAs for rifabutin and rifampicin just attained significance ( P = 0.05) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities. Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin. The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro. Des patients atteints de tuberculose pulmonaire frottis positif non-traités antérieurement ont été répartis au hasard pour un traitement aux doses respectives de 600, 300, 150 ou 75 mg de rifabutin (LM427, ansamycine), de 600, 300 ou 150 mg de rifampicine, de 300 mg d'isoniazide ou à l'absence de traitement quotidien, pendant deux jours. La baisse des numérations viables de Mycobacterium tuberculosis dans les recueils d'échantillons de crachats pendant les 2 jours, nommée activité bactéricide précoce (ABP), était estimée à partir des numérations des unités formant colonies (ufc) sur un milieu en gélose 7H-11 sélectif. L'ABP pour la rifabutin a varié de −0,039 (augmentation des numérations) à 0,049 log 10 ufc/ml/jour, tandis que l'ABP a augmenté de 0,071 pour 150mg de rifampicine à 0,293 log 10 ufc/ml/jour pour 600mg de rifampicine, et 0,43 log 10 ufc/ml/jour pour 300mg d'isoniazide. La différence entre les ABP pour rifabutin et rifampicine a juste atteint sa valeur significative ( P = 0,05), ce qui suggère que la rifabutin était inactive ou moins active que la rifampicine contre les bacilles extracellulaires d