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.

The general medical community in the United States has been rather slow in adopting short-course bactericidal chemotherapy for tuberculosis despite the clear demonstration of the advantage by several carefully controlled clinical trials. Reported herein is experience between January 1976 and December 1982 in 1,028 patients with bacteriologically proved pulmonary tuberculosis treated for nine months with isoniazid (300 mg) and rifampin (600 mg) daily for one month followed by twice-weekly isoniazid (900 mg) and rifampin (600 mg) for the other eight months. They were treated by 45 local practitioners and supervised by public health nurses through 60 Arkansas Department of Health chest clinics in the state. Outpatient therapy was mostly self-administered in the routine treatment program. Overall success was achieved in 95 percent of the 751 patients who completed therapy; in 21 (2.8 percent), sputum cultures failed to convert to negative, and 15 (2.1 percent) have had relapse since therapy was stopped. Therapy could not be completed in 26.9 percent due to deaths, drug toxicities, relocation, refusal, etc. Of 21 bacteriologic failures, 18 patients developed isoniazid resistance and were treated with additional two bactericidal drugs. Most of the relapses (nine of 15) occurred within 12 months after chemotherapy was stopped. However, four relapses occurred quite late during follow-up. Only three of 15 patients with relapse showed isoniazid resistance. Side effects of the drugs were encountered in 10.3 percent, but major toxicities occurred in 3.2 percent (hepatitis in 2.6 percent, hematologic effects in 0.6 percent). Clinical surveillance for toxicity is preferred over routine and regular biochemical monitoring. Patient acceptance of the regimen was excellent, and compliance was good. Short-course chemotherapy is effective, with low drug toxicity, reduced cost of drugs, and ease of direct supervision when needed, and is acceptable to patients in routine treatment.

Short-course, largely twice-weekly chemotherapy for tuberculosis was introduced in the United States for treatment of adults with pulmonary disease by the Arkansas State Department of Health in 1976. Since 1977, 50 children with tuberculosis have been treated with rifampin, 10 to 20 mg/kg, and isoniazid, 10 to 20 mg/kg daily for one month followed by 10 to 20 mg/kg of rifampin and 20 to 40 mg/kg of isoniazid twice a week for another 8 months. Ages ranged from 4 months to 15 years with a median age of 3 years. A presumptive diagnosis of tuberculosis was made on the basis of 10 mm or more of induration to 5 TU of purified protein derivative and a chest film or other findings compatible with tuberculosis. Three children had extrapulmonary disease (two had cervical adenitis, one had tuberculosis arthritis). Of the 47 children with pulmonary disease, 32 were asymptomatic. The results were excellent. Symptoms cleared in 1 to 2 months. Most pulmonary infiltrates had cleared by 10 months, but hilar adenopathy rarely cleared in less than 2 years. Drug toxicity occurred in only one patient (vomiting of rifampin). This treatment appears to be safe, effective, inexpensive, short and simple enough to ensure cooperation or to allow personnel to administer drugs directly to children from socially disorganized families.

Although short-course, largely twice weekly chemotherapy for treatment of tuberculosis has been shown to be effective in other countries, when given under closely controlled conditions, it has not been adopted in this country where most patients are older and are treated as outpatients. Since January, 1976, 315 patients (mean age 55.5 years) with proven pulmonary tuberculosis have been treated with rifampin (RIF) 600 mg and isoniazid (INH) 300 mg daily for one month, followed by RIF 600 mg and INH 900 mg twice-weekly for another eight months, self-administered except for a few patients. By three months, 95 percent had converted to negative culture. There were only ten failures among 185 patients in whom final results could be assessed. There has been only one relapse during 1-21 months of follow-up in 175 patients. Serious side effects were few: six instances of jaundice, two of "flu-like syndrome," and one of thrombocytopenia. This form of initial therapy for tuberculosis is safe, effective, and economical.

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.