Although most childhood tuberculosis occurs in developing countries, cases are still encountered in the United States, especially among new-immigrant populations. Guidelines for treatment of childhood tuberculosis have been based on studies of adult therapies. The most commonly used regimen is six months of isoniazid and rifampin, supplemented during the first two months with pyrazinamide. Usually therapy is administered daily during the first two months and twice weekly during the remaining treatment course. Al-Dossary and associates conducted an observational trial to determine the effectiveness of a six-month, directly observed therapy (DOT) regimen in children with tuberculosis.
The authors studied a DOT course for pulmonary, pleural, and lymph-node tuberculosis. The regimen began with two weeks of daily isoniazid, rifampin, and pyrazinamide; then six weeks of the same combination twice weekly, followed by 16 weeks of twice-weekly isoniazid and rifampin without pyrazinamide. After excluding children likely to have drug-resistant tuberculosis and those with human immunodeficiency virus infection or previous treatment for tuberculosis, 175 children from five months to 17 years of age received the trial regimen (see the accompanying table). During the first two weeks, all but the weekend doses were given as DOT. A good response was defined as improvement in symptoms, weight gain, improvement by physical examination or chest radiography, and adherence to treatment. A relapse was defined as a positive culture after the conclusion of treatment.
The treatment regimen was well tolerated. The most common adverse responses were mild abdominal discomfort or vomiting. Ten percent of patients required extended treatment because of slow response or worsening of disease. Resolution of tuberculosis is characteristically slow, and complete resolution may be difficult to evaluate at the end of therapy. Some of the children received extended treatment although it was unclear whether they really needed additional medication. The tested regimen, however, compared favorably with other regimens currently in use.
The authors conclude that this three-drug, six-month DOT regimen for pediatric tuberculosis is effective and well tolerated. Inherent difficulties in analyzing tuberculosis treatment results are caused by the long time required to definitively identify resolution. Therefore, further testing of this regimen is recommended.
editor's note: Standard therapy for children with tuberculosis involves the use of isoniazid in combination with other medications. The goal of treatment is to kill the mycobacterium in the shortest period of time. More intensive multiple-drug combinations such as isoniazid, rifampin, and pyrazinamide have resulted in successful six- and nine-month treatment regimens in children. When drug resistance is suspected, additional medication can be used, and therapy may be extended to 18 months. DOT is a highly effective and relatively inexpensive way to ensure that a child is adequately treated. Newer regimens are simplifying DOT by decreasing the number of weekly doses. With these easier regimens, DOT should become the standard of care for treatment of children with tuberculosis.—r.s.