Chemotherapy for Tuberculosis in Infants and Children

Active tuberculosis is diagnosed in more than 1100 children annually in the United States. The therapy for patients with tuberculosis has undergone major changes during the past decade, including demonstration of the efficacy of multidrug, short-course chemotherapy for pulmonary tuberculosis in adults.1 At least nine studies of 6-month antituberculosis chemotherapy have demonstrated comparable results in children.2-10 The purpose of this statement is to give revised recommendations for treatment of tuberculosis in infants and children. These recommendations have been formulated in collaboration with the Division of Tuberculosis Elimination of the Centers for Disease Control and the American Thoracic Society. MICROBIOLOGIC RATIONALE FOR TREATMENT Laboratory observations of Mycobacterium tuberculosis and clinical therapy trials have led to a hypothesis concerning the populations of tubercle bacilli and the actions of various antimycobacterial drugs and drug combinations.11,12 Mycobacteria replicate slowly, can remain dormant for prolonged periods, and can be killed by drugs only during replication. In the host, bacilli live in several sites: open cavities, closed caseous lesions, and within macrophages. Each site contains bacilli with a different population size, metabolic activity, and rate of replication. Open cavities, which are rare in infants and children, have the largest number of mycobacteria. Naturally occurring drug-resistant mutants of M tuberculosis occur within large bacterial populations even before chemotherapy is started. The number of drug-resistant mutants is proportional to the size of the mycobacterial population; thus, they are common in open cavities, but less common in caseous lesions and within macrophages. Mutants naturally resistant to two drugs are virtually nonexistent.