Smear- and culture-negative pulmonary tuberculosis: four-month short-course chemotherapy.

Patients with positive tuberculin reaction, abnormal chest radiograph, and negative bacteriology are often treated empirically for tuberculosis (TB) after exclusion of other causes. Therapy generally consists of two bactericidal drugs (rifampin [RIF] and isoniazid [INH]) for 9 months or INH for 9 to 12 months. With such a small bacillary population, even less therapy might suffice. Thus we began in January 1980 to discontinue therapy at 4 months when there was sufficient evidence of a paucity of bacilli demonstrated by at least three negative smears and cultures for TB at the start of therapy. To date, 452 such patients have been so treated. Radiographic abnormalities included pulmonary infiltration of varying extent, pleural residuals, and hilar adenopathy. The full course of therapy could not be completed in 38 (8.4%) patients due to death, relocation, or drug toxicity. Side effects of the drugs occurred in 21 (4.7%) patients, but toxic hepatitis occurred in only four (0.9%) patients. Thus, 414 patients completed the full 4-month course of therapy. Of these, 126 (30.4%) patients showed radiographic and/or clinical response suggesting active infection. The remainder showed no such improvement, suggesting either a mistake in diagnosis or dormant TB. During follow-up of the 414 patients from 6 to 78 months (median, 44 months), five (1.2%) patients relapsed: three among responders and two among nonresponders. Thus, among persons suspected of having TB but with negative bacteriology, 4 months of chemotherapy with INH and RIF gave results comparable to those achieved with 9 months of therapy in smear- and culture-positive cases.