Monitoring Treatment of Childhood Tuberculosis and the Role of Therapeutic Drug Monitoring.

Most children tolerate the first-line antibiotics used to treat Mycobacterium tuberculosis (TB) very well. The most common adverse effect is gastrointestinal distress unrelated to hepatotoxicity; the latter is seen in less than 1% of children. Despite the infrequency of hepatotoxicity, the potential long-term impact of hepatic insufficiency dictates that all children receiving antimycobacterial therapy should be evaluated periodically by symptom screening and physical examination. Routine measurement of transaminases in previously healthy, asymptomatic children is discouraged, as up to 40% of children will have transient, asymptomatic transaminase elevation that should not alter clinical management; measurement of serum liver enzymes is reserved for children who develop symptoms and those with existing liver disease or taking other potentially hepatotoxic drugs. Caregivers and personnel distributing directly-observed therapy need to be cognizant of potential drug toxicities and have a clear understanding of what to do if a child develops symptoms. There are substantial inter-patient variations in serum antibiotic concentrations when the same milligram per kilogram dose is given to different children of varying ages and sizes, reflecting differences in drug absorption and metabolism. While these variations may not impact the outcome of previously healthy children with mild disease, outcomes for children with human immunodeficiency virus infection or severe disease can be worse if sub-therapeutic drug concentrations are achieved. Therapeutic drug monitoring, wherein serum drug concentrations are used to optimize medication doses, should be considered for children with severe disease or if there is concern about alterations in drug absorption or metabolism.