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Isoniazid-resistant Tuberculosis in Children: A Systematic Review

Yuen, Courtney M. PhD*; Tolman, Arielle W. BA*; Cohen, Ted MD, DrPH†‡; Parr, Jonathan B. MD, MPH*†§; Keshavjee, Salmaan MD, PhD*†§; Becerra, Mercedes C. ScD*†§

The Pediatric Infectious Disease Journal: May 2013 - Volume 32 - Issue 5 - p e217–e226
doi: 10.1097/INF.0b013e3182865409
Antimicrobial Reviews

Background: Isoniazid resistance is an obstacle to the treatment of tuberculosis disease and latent tuberculosis infection in children. We aim to summarize the literature describing the risk of isoniazid-resistant tuberculosis among children with tuberculosis disease.

Methods: We did a systematic review of published reports of children with tuberculosis disease who had isolates tested for susceptibility to isoniazid. We searched PubMed, Embase and LILACS online databases up to January 12, 2012.

Results: Our search identified 3403 citations, of which 95 studies met inclusion criteria. These studies evaluated 8351 children with tuberculosis disease for resistance to isoniazid. The median proportion of children found to have isoniazid-resistant strains was 8%; the distribution was right-skewed (25th percentile: 0% and 75th percentile: 18%).

Conclusions: High proportions of isoniazid resistance among pediatric tuberculosis patients have been reported in many settings suggesting that diagnostics detecting only rifampin resistance are insufficient to guide appropriate treatment in this population. Many children are likely receiving substandard tuberculosis treatment with empirical isoniazid-based regimens, and treating latent tuberculosis infection with isoniazid may not be effective in large numbers of children. Work is needed urgently to identify effective regimens for the treatment of children sick with or exposed to isoniazid-resistant tuberculosis and to better understand the scope of this problem.

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From the *Department of Global Health and Social Medicine, Harvard Medical School; Division of Global Health Equity, Brigham and Women’s Hospital; Department of Epidemiology, Harvard School of Public Health; and §Partners In Health, Boston, MA.

C.M.Y., A.W.T. and M.C.B. designed the study. C.M.Y., A.W.T. and J.B.P. participated in data extraction. C.M.Y. analyzed the data. T.C. and S.K. guided data interpretation. C.M.Y. and M.C.B. wrote the article draft and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in article revisions and approved the final article.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Mercedes C. Becerra, ScD, Department of Global Health and Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, MA 02115. E-mail:

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© 2013 Lippincott Williams & Wilkins, Inc.