The efficacy of short-course chemotherapy for tuberculosis

Short-course tuberculosis chemotherapy regimens generally depend on direct drug action against tubercle bacilli within cells and solid caseous materials that are multiplying only slowly or intermittently. In this they tend to differ from the old, traditional 12-month regimens, which attack actively growing bacterial populations while relying mainly on natural host defenses to reduce the bacilli within cells and solid caseous materials. The drug pyrazinamide (PZA) has a strong bactericidal effect on intracellular tubercle bacilli, and its addition to the conventional isoniazide-streptomycin (INH-SM) combination considerably reduces the incidence of relapses occurring after a short (6 or 9 month) course of treatment. In addition, the drug rifampicin (RMP) has a bactericidal effect on tubercle bacilli multiplying slowly or intermittently inside macrophages and solid caseous materials. All studies conducted to date have shown 6 months of therapy with INH-RMP to entail relapse rates of 5 per cent or less, and have shown 9 months of therapy with this combination to produce complete success. Furthermore, a clinical trial has proven that addition of SM and PZA can significantly increase the effectiveness of this INH-RMP combination, and the findings of a 1978 study suggest that an initial two-month phase of treatment with all four drugs (SM, PZA, INH, and RMP) followed by a four-month phase of continued treatment with RMP may be 100 per cent effective. So far it has not been demonstrated that any additional drug supplementing INH + RMP can make further inroads against the disease during the four-month continuation phase. Courses of treatment shorter than 6 months have generally involved unacceptably high relapse rates. However, for smear-negative culture-negative patients, short-course SM-INH-RMP-PZA regimens lasting 2 and 3 months have produced acceptable results. INH and RMP cannot be given together in all retreatment regimens, because most patients will harbor organisms resistant to one or both. Instead, a companion drug of INH or RMP (either PAS or ethambutol) should be employed. There is not yet any direct proof that addition of SM and PZA to such retreatment regimens would greatly improve the effectiveness of these regimens; but at least in the case of RMP-ethambutol regimens, our present knowledge makes it logical to assume that a marked increase in effectiveness would occur.