Search

We have shown that 6-month therapy with isoniazid (INH) and rifampin (RIF) is adequate for pulmonary tuberculosis when tubercle bacilli are less numerous, i.e., smear negative, culture positive. Tuberculous exudative pleural effusion contains small bacterial populations, as often demonstrated by negative smears and fewer positive cultures. Therefore, in 1980, we started treating tuberculous pleural effusion with a therapy protocol consisting of INH 300 mg plus RIF 600 mg daily for 1 month, followed by INH 900 mg plus RIF 600 mg twice weekly for another 5 months (total, 6 months). From January 1980 to September 1990, 198 patients with an average age of 62.6 years were treated in this manner. Associated pulmonary infiltration was present in 92 patients, of whom 50% yielded positive sputum cultures. Other medical conditions as "risk factors" were present in 30%. Therapy was not completed in 36 patients because of death, relocation, noncompliance, and drug side effects. Treatment failed during therapy in only 1 patient. Side effects of the drugs occurred in 13 (6.6%) patients, but major side effects were encountered in only three (1.5%), two with toxic hepatitis and one with thrombocytopenia. The full 6-month therapy was completed by 161 patients. During follow-up from 2 to 133 months (median, 46 months), none of the 161 patients had relapse. An overall success rate of 99% was achieved in 162 patients with only 1 failure during therapy. Thus, 6-month therapy with INH plus RIF is adequate in tuberculous exudative pleural effusion, even when associated with smear-negative (3 specimens) culture-positive pulmonary tuberculosis.

We have shown in Arkansas that 9 months of therapy with isoniazid (INH) and rifampin (RIF) can achieve lasting success in 95% of cases with sputum-smear-positive pulmonary tuberculosis. It seemed likely that when the tubercle bacilli were less numerous, i.e., could not be seen on microscopy, less therapy would suffice. Thus, in January 1980, we began giving only 6 months of treatment to patients in whom at least one sputum culture showed M. tuberculosis but at least three sputum smears showed no organisms. The regimen for adults is INH 300 mg and RIF 600 mg daily for 1 month followed by INH 900 mg and RIF 600 mg twice weekly for another 5 months. To date, 286 patients with an average age of 68.2 yr have been treated in this manner. Associated medical conditions were present as "risk factors" in 23.7%. The full course of therapy could not be completed in 75 patients (26.2%), largely because of side effects of the drugs and non-TB deaths in this group of elderly patients. Side effects of the drugs requiring change of drug(s) occurred in 33 patients (11.5%), but major side effects occurred in only eight (2.8%), four (1.4%) with toxic hepatitis and four with hematologic toxicity. The side effects in 25 patients (8.7%) were not life-threatening and were due to drug intolerance. Treatment failed during therapy in only one patient. The full 6-month course of therapy was completed by 211 patients. During follow-up from 3 to 107 months (median, 45 months), five of 211 patients (2.4%) relapsed, all with drug-susceptible organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

To evaluate the possibility of separate pulmonary infections in human beings by different strains of Mycobacterium tuberculosis, a search for multiple phage types within a single host was under-taken. Culture isolates from 2 or more distinct anatomic sites of infection in the same patient were obtained from 87 persons. In 3 subjects, 2 distinct phage types were found. The possible explanations for 2 types in the same patient and the epidemiologic implications are discussed.

Between January 1976 and June 1981, 814 patients with pulmonary tuberculosis were treated for 9 months with isoniazid (INH) and rifampin (RIF), daily for 1 month and twice weekly for the other 8 months. Overall success was achieved in 95% of the 586 patients who completed therapy: in 15 patients (2.9%), sputum cultures failed to convert to negative during therapy, and 10 patients (1.7%) have relapsed since stopping the chemotherapy. Major toxic effects occurred in 22 patients; in 14 during the daily phase and in 8 during the twice-weekly phase. Hepatic toxicity occurred in 13 patients during daily and in 5 during twice-weekly treatment, and it was caused by RIF in 5, INH in 10, and was undetermined in 3. Hematologic abnormalities developed in 4 patients: in 1 during the daily and in 3 during the twice-weekly phase. Minor side effects, which were not life threatening, were encountered in 62 patients: in 35 during the daily and in 27 during the twice-weekly therapy. These were gastrointestinal intolerance in 18, drug fever in 27 (including 11 with "flu-syndrome" during twice-weekly administration), cutaneous rashes in 14, and headache, general malaise, and weakness in 3. These side effects were produced by RIF in 43, by INH in 18, and the responsible drug was not identified in 1. Hypersensitivity reactions to twice-weekly administration of RIF were infrequent. Clinical surveillance for toxicity is preferred over routine and regular biochemical monitoring.