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Am Fam Physician. 2008;77(7):1018-1020

Background: The American Academy of Pediatrics recommends that children and adolescents with latent tuberculosis (TB) infection be treated with a nine-month regimen of daily isoniazid (Nydrazid) therapy. Patient compliance with prolonged therapy is difficult; even six-month isoniazid regimens generally have compliance rates of less than 60 percent. This low compliance rate has major implications for the development of resistant TB strains. However, other countries have successfully used shorter treatment regimens for latent TB infection. For example, the British Thoracic Society recommends a three-month isoniazid/rifampin (Rifamate) regimen for children and adolescents. Because it is well documented that treatment duration is inversely related to compliance, establishing an effective shorter treatment course could positively improve outcomes for children with latent TB infection. Spyridis and colleagues compared a shorter course of isoniazid/rifampin combination therapy with a longer course of isoniazid monotherapy.

The Study: The prospective, randomized controlled study included children younger than 15 years who were diagnosed with latent TB infection. Patients were enrolled in the study during one of two consecutive four-year periods between January 1995 and December 2002. Participants had positive tuberculin skin test results, were asymptomatic, and had normal chest radiograph findings or radiograph findings that indicated inactive fibrotic or calcified lymph node lesions. Patients enrolled during the first period were randomly assigned to receive isoniazid for nine months or isoniazid/rifampin for four months. Patients enrolled during the second period were randomly assigned to receive isoniazid/rifampin for three or four months. Doses for both medications were 10 mg per kg per day. Treatment compliance was confirmed using urine testing. Clinical outcomes were monitored for up to 11 years after completion of treatment.

Results: Final analysis included 926 patients with a mean age of 8.7 years. Overall, 850 participants (91.8 percent) had excellent or moderate compliance rates, although significantly lower compliance rates occurred in patients receiving the nine-month isoniazid regimen compared with the other groups. No patient in any group progressed to active TB during the study or follow-up period, and no serious drug-related adverse events were reported. Six percent of patients receiving the long-term regimen had transient liver enzyme elevations compared with 1.2 percent in the short-term treatment groups, and 6.5 percent of patients receiving the long-term regimen developed nausea and epigastric pain compared with 0.7 percent in the short-term treatment groups. In addition, 2 percent of patients in the short-term treatment groups developed photosensitivity reactions or transient maculopapular rashes. Treatment discontinuation was not required in any patient.

Conclusion: The authors conclude that a three- to four-month course of isoniazid/rifampin combination therapy is well tolerated in children and is as effective as the traditional nine-month course of isoniazid monotherapy. In addition, the shorter treatment courses are associated with higher compliance rates.

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