Singapore Study of Intermittent Rifampicin Plus Isoniazid for Pulmonary Tuberculosis
In Singapore, 481 adult patients with newly diagnosed pulmonary tuberculosis were allocated at random to four regimens of intermittent rifampicin plus isoniazid. All patients received an initial two weeks of daily chemotherapy with streptomycin plus isoniazid plus rifampicin in standard daily dosages, followed by isoniazid 15 mg/kg body weight plus rifampicin 900 mg, both drugs twice a week (HR2 regimen) or once a week (HR1 regimen), or by isoniazid 15 mg/kg plus rifampicin 600 mg, both drugs twice a week (LR2 regimen) or once a week (LR1 regimen). All patients in addition received a supplementary daily capsule containing at random either rifampicin 25 mg or a matched placebo, to see if the daily supplement would reduce the incidence of adverse reactions to rifampicin.
The first 334 patients with fully drug-sensitive strains pretreatment were currently available for assessment at 12 months. Every single patient on the 2 twice-weekly regimens had a favourable bacteriological status at 12 months, as had 96% of the HR1 and 92% of the LR1 patients. Adverse reactions to intermittent rifampicin occurred in 26% of the HR1 patients, but on the other three regimens their incidence was low. In contrast, the incidence of rifampicin-dependent antibodies ranged from 21% (LR2) to 54% (HR1). The incidence of adverse reactions and antibodies was unaffected by the rifampicin supplement.
KeywordsPulmonary Tuberculosis Tuberculosis Treatment Rapid Acetylators Rifampicin Resistance Dose Size
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