Short-course therapy for tuberculosis.

Abstract

The discovery of rifampicin was the turning point away from the standard long term treatment for tuberculosis of 18 to 24 months and towards a 6-month curative programme. Rifampicin has proven to be highly effective and vital to short-course tuberculosis therapy, but its disadvantage is its cost. This makes it relatively unavailable where it is most needed, i.e. in countries where tuberculosis is still rampant, but which are economically underdeveloped. In such areas other needs take precedence over a chronic and non-spectacular medical condition like tuberculosis. During the past 10 years pyrazinamide has been 'rediscovered' and restudied, and when used in combination with rifampicin has been shown to play an important role in short-course chemotherapy. Its contribution to efficacy does not appear to extend beyond the first 2 months of therapy, and it should be discontinued after 2 months. This relatively short administration period helps to minimise adverse reactions to the drug. The main measure of success in short-course chemotherapy is the relapse rate, and this has been higher, sometimes unacceptably so, in regimens where bacteriostatic drugs were substituted for bactericidal ones. In conclusion, isoniazid, rifampicin and pyrazinamide in combination may be deemed essential to an effective short-course regimen of 6 months' duration. Curtailing the duration of treatment to less than 6 months in smear-positive tuberculosis results in high relapse rates and thus is not acceptable. Several studies have been undertaken varying the drug combinations, the dosages and the drug administration routines (i.e. whether daily followed by intermittent or intermittent throughout), in an effort to arrive at the simplest, most effective, least toxic and most economical all-round treatment programme. Such studies are still in progress. When recommended dosage regiments are followed, the incidence of adverse reactions is low with short-course therapy, and in only 5% or less of patients is it necessary to withdraw one or more drugs.