Rifabutin for the treatment of newly-diagnosed pulmonary tuberculosis: a multinational, randomized, comparative study versus Rifampicin. Rifabutin Study Group. Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis. A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis. A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis. A controlled study of rifabutin and an uncontrolled study of ofloxacin in the retreatment of patients with pulmonary tuberculosis resistant to isoniazid, streptomycin and rifampicin. Hong Kong Chest Service/British Medical Research Council. [Preliminary results of rifabutine (ansamycine LM 427) treatment of patients with newly detected and chronic pulmonary tuberculosis and Mycobacterium infections].
Patients with newly-diagnosed drug-sensitive, radiographically active and bacteriologically confirmed pulmonary tuberculosis recruited at 6 centres in Argentina, Brazil and Thailand.
                To assess the efficacy, tolerability and toxicity of two regimens containing different daily dosages of rifabutin in comparison with rifampicin.
                Multicentred, randomised, comparative study. In each group, study medications were administered daily for 6 months combined with isoniazid (6 months), and with pyrazinamide and ethambutol (both stopped after 2 months). Treatment success patients were followed-up for up to 2 years.
                A total of 520 patients were enrolled and randomly assigned to receive either rifampicin (n = 175), or rifabutin 150 mg (n = 174) or rifabutin 300 mg (n = 171). Considering all patients with positive baseline culture, the success rates at the last valid observation for each patient were 89%, 94% and 92% in the rifampicin, rifabutin 150 mg, and rifabutin 300 mg groups, respectively. The median time to culture conversion was comparable in the 3 groups and was 34 days for rifampicin and 37 days for each of the rifabutin groups. During the drug-free follow-up period, one relapse occurred in the rifampicin group, and two in each of the rifabutin groups. The 3 treatment schedules appeared well tolerated. No patients had to discontinue therapy because of an adverse event in the rifabutin 150 mg group, compared to one in the rifampicin and 5 in the rifabutin 300 mg group.
                All 3 regimens proved effective and well tolerated. Rifabutin at 150 mg/d showed the best risk-to-benefit ratio, in that this group had the highest proportion of patients completing treatment, the highest bacteriological conversion rates and the lowest incidence of adverse events. The efficacy and safety of rifabutin (RBT) and rifampicin (RMP) were compared in 298 patients with newly diagnosed pulmonary tuberculosis. In the initial 8-wk phase, all patients received isoniazid 400 mg/d, ethambutol 1200 mg/d, and pyrazinamide 2 g/d and were randomly allocated to receive either RMP 600 mg/d or RBT 300 mg/d. In the 16-wk continuation phase, patients received intermittent treatment (twice weekly) with isoniazid 600 mg/d, ethambutol 2400 mg/d and either RMP 600 mg/d or RBT 300 mg/d. Two hundred twenty-five (RMP = 118; RBT = 107) patients completed the 24-wk treatment period (evaluable patient population). Bacteriologic conversion rates in the RMP and RBT groups were 87.7 versus 92.0% at Week 8, 99.1 versus 99.0% at Week 12, 93.5 versus 93.8% at Week 24, and 89.8 versus 95.3% at the last valid observation. The mean time to first bacteriologic conversion was 14.1 wk in the RMP group and 14.3 wk in the RBT group. None of these differences was significant. Adverse events were reported by four patients (five events) in the RMP group and six patients (six events) in the RBT group. Those events thought to be associated with RMP were increased SGOT and leucopenia and, with RBT, increased SGOT and thrombocytopenia. Two hundred four patients entered the follow-up phase, and, of these, 95 (RMP = 49; RBT = 46) completed the scheduled 24-mo period. The overall rate of relapse was 3.8% (4/106) for the RMP group and 5.1% (5/98) for the RBT group. These differences were not significant. All relapsed patients, except for two who could not be traced, were successfully retreated. We conclude that the efficacy and tolerability of RBT is equivalent to that of RMP in the treatment of newly diagnosed uncomplicated tuberculosis, and that RBT can be effectively administered in a part-daily, part-intermittent dosage schedule. This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic.
                To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB.
                Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide.
                Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated with a longer sputum conversion time for patients treated with either regimen. No major adverse events requiring dosage reduction or withdrawal of any study medication were seen in either treatment group. Mean absolute peripheral blood CD4 T lymphocyte counts increased by 28% from week 0 to week 12 in all subjects (334-427/microliters, respectively). An unexpected finding was the isolation of Mycobacterium africanum from 49% of the sputum cultures. This is the first report indicating a high prevalence of M. africanum in human TB in Uganda.
                Short-course antituberculosis regimens containing rifabutin or rifampicin are both safe and efficacious in the treatment of HIV-1 associated tuberculosis. Rifabutin-containing regimens were associated with earlier sputum smear and culture conversion. A study of rifabutin in the retreatment of patients with chronic pulmonary tuberculosis whose strains of tubercle bacilli were resistant to all three of the drugs isoniazid, streptomycin, and rifampicin, and usually to others as well, was undertaken in 22 Chinese patients in Hong Kong. They were arranged in 11 pairs such that the resistance pattern of the strains for both patients was the same or closely similar. One of each pair was allocated at random to receive rifabutin (B) daily and the other rifampicin (R) daily. The two members of each pair were also prescribed the same or similar companion drugs, selected on the basis of the results of susceptibility tests and of the history of previous antituberculosis chemotherapy. The bacteriological results showed no evidence of a sustained benefit in any patient. A temporary response was seen on sputum smear examination in 14 patients (7B, 7R), of whom 10 (5B, 5R) had a period of smear-negativity, and on sputum culture examination in 10 patients (5B, 5R), of whom 3 (2B, 1R) had a period of culture-negativity. The duration of response was longer for the B patient in 5 pairs and for the R patient in 5. Two patients (both B) had rifabutin-susceptible strains on admission to the study; their temporary responses were among the best and were associated with the emergence of rifabutin resistance, suggesting that rifabutin may have contributed to their response. A total of 17 patients, including 7 not in the paired comparison, were subsequently retreated with ofloxacin; 10 showed a response, disease becoming and remaining quiescent in 3.(ABSTRACT TRUNCATED AT 250 WORDS) nan
The replacement of rifampicin by rifabutin for first-line treatment of tuberculosis is not supported by the current evidence. HIV-positive people with tuberculosis, the group most likely to benefit from the rifabutin use, are under-represented in trials to date, and further trials in this group would be useful.