Background The diagnosis of drug-resistant tuberculosis (DR-TB) in children is challenging and treatment is associated with many adverse effects.

Objective We aimed to assess if careful observation, without initiation of second-line treatment, is safe in asymptomatic children referred with ‘culture-confirmed’ DR-TB.

Setting KwaZulu-Natal, South Africa—an area with high burdens of HIV, TB and DR-TB.

Design, intervention and main outcome measures We performed an outcome review of children with ‘culture-confirmed’ DR-TB who were not initiated on second-line TB treatment, as they were asymptomatic with normal chest radiographs on examination at our specialist referral hospital. Children were followed up every other month for the first year, with a final outcome assessment at the end of the study.

Results In total, 43 asymptomatic children with normal chest radiographs were reviewed. The median length of follow-up until final evaluation was 549 days (IQR 259–722 days); most (34; 83%) children were HIV uninfected. Resistance patterns included 9 (21%) monoresistant and 34 (79%) multidrug-resistant (MDR) strains. Fifteen children (35%) had been treated with first-line TB treatment, prior to presentation at our referral hospital. At the final evaluation, 34 (80%) children were well, 7 (16%) were lost to follow-up, 1 (2%) received MDR-TB treatment and 1 (2%) died of unknown causes. The child who received MDR-TB treatment developed new symptoms at the 12-month review and responded well to second-line treatment.

Conclusions Bacteriological evaluation should not be performed in the absence of any clinical indication. If drug-resistant Mycobacterium tuberculosis is detected in an asymptomatic child with a normal chest radiograph, close observation may be an appropriate strategy, especially in settings where potential laboratory error and poor record keeping are constant challenges.