Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study.

BACKGROUND: Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome. METHODS: In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause. RESULTS: One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age