Failure of chemoprophylaxis with standard antituberculosis agents in child contacts of multidrug-resistant tuberculosis cases.

BACKGROUND: There is little published information on optimal chemoprophylaxis for children with multidrug-resistant tuberculosis (MDR-TB) contacts. Current guidelines of World Health Organization suggest that isoniazid (INH), the standard first-line chemoprophylaxis, be used for those exposed to MDR-TB.

METHODS: This is a retrospective review of medical records of 5 children residing in the Western Cape Province, South Africa, who developed MDR-TB while receiving conventional chemoprophylaxis with either INH or a combination of INH, rifampin, and pyrazinamide.

RESULTS: Adult MDR-TB source cases were identified for all children and resistance patterns of patient and source case isolates matched in all cases. The median age of the patients was 0.4 years. One patient participated in a trial of INH chemoprophylaxis for HIV-infected children. Four HIV-uninfected infants presented with TB-related symptoms several months after being given chemoprophylaxis because of a known source case. Stigmata of TB were cough >3 weeks in 4, weight loss or a history of failing to thrive in 3, fever in 2 infants, and reported night sweats in 1. Chest radiographs at diagnosis revealed lymphadenopathy, lobar opacification, and airway narrowing. All patients were treated for varying time periods at a TB referral institution in the Western Cape.

CONCLUSIONS: Standard, first-line anti-TB agents were inadequate to prevent MDR-TB in children exposed to MDR-TB contacts. Second-line chemoprophylaxis, reflecting the susceptibility profile of the source case's isolate, with at least 2 drugs with activity against the drug-resistant isolate for 6-12 months should be considered.