, et al
Safety and side effects of rifampin versus isoniazid in children
N Engl J Med
; doi:

Investigators from multiple institutions conducted a randomized controlled trial to compare the safety of 4 months of rifampin treatment to 9 months of isoniazid treatment for latent tuberculosis in children. Participants 0–17 years old were enrolled at study sites in several countries. Youth were eligible if they had a positive screening test result. Children <5 years old with a negative tuberculin skin test (TST) who had a household contact with tuberculosis were also enrolled but were excluded from the analysis if their TST remained negative for 8 weeks following treatment of the household contact and their provider opted to stop treatment.

Study participants were randomized to 9 months of isoniazid treatment (10–15 mg/kg/day) or 4 months of rifampin treatment (10–20 mg/kg/day). Treatment adherence was assessed by pill counts at study visits; per-protocol treatment completion was defined as a participant receiving >80% of prescribed doses. The primary study outcome was adverse events related to drug treatment. Adverse events were classified as either leading to discontinuation of the study drug or minor symptoms related to treatment. Secondary outcomes included development of active tuberculosis and rates of per-protocol treatment completion. Regression analyses were used to estimate risk differences in these outcomes between children in the 2 treatment groups; clustering for children within families was accounted for in the regression models.

A total of 844 participants were enrolled, but 15 children <5 years old exposed to a household contact with tuberculosis were excluded because they never developed a positive TST. The median age of the remaining 829 participants was 10.2 years; 422 received rifampin and 407 were randomized to isoniazid. There were no adverse events that led to discontinuation of the study drug in either treatment group. Rates of any minor symptom possibly related to the study drug were 4.4% among those in the rifampin group and 4.2% for those receiving isoniazid (adjusted risk difference, 0.3%; 95% CI, −1.7% to 2.4%). Youth randomized to rifampin were significantly more likely to complete treatment per protocol than were those in the isoniazid group (85.3% and 76.4%, respectively; adjusted risk difference, 13.4%; 95% CI, 7.5%–19.2%). Two participants in the isoniazid treatment group developed active tuberculosis versus none in the rifampin group (adjusted risk difference comparing rifampin to isoniazid, −0.37 cases per 100 person-years; 95% CI, −0.88 to 0.14).

The authors conclude that in children <18 years old, 4 months of rifampin treatment for latent tuberculosis had similar efficacy and safety as did 9 months of isoniazid treatment and was associated with better treatment adherence.

Dr Lesser has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Latent infection with Mycobacterium tuberculosis occurs commonly worldwide and has a high incidence in...

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