{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T21:17:07Z","timestamp":1773523027096,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Global Tuberculosis Programme"},{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"crossref","award":["2020\/1079860-0"],"award-info":[{"award-number":["2020\/1079860-0"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"crossref","award":["GM007546"],"award-info":[{"award-number":["GM007546"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization\u2013recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged &amp;lt;18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%\u201395%). At World Health Organization\u2013recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children \u22646 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9\u201318.8] vs 22.0 [13.8\u201330.1] \u03bcg\u00b7h\/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4\u201323.2] vs 26.5 [21.3\u201331.7] \u03bcg\u00b7h\/mL). Heterogeneity and small sample sizes were major limitations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and\/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac973","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T19:01:20Z","timestamp":1673118080000},"page":"1658-1670fc","source":"Crossref","is-referenced-by-count":5,"title":["Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis"],"prefix":"10.1093","volume":"76","author":[{"given":"Bel\u00e9n P","family":"Solans","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine , San Francisco, California , USA"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agathe","family":"B\u00e9ranger","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine , San Francisco, California , USA"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendra","family":"Radtke","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine , San Francisco, California , USA"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine , San Francisco, California , USA"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuad","family":"Mirzayev","sequence":"additional","affiliation":[{"name":"Global Tuberculosis Programme, World Health Organization , Geneva , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Medea","family":"Gegia","sequence":"additional","affiliation":[{"name":"Global Tuberculosis Programme, World Health Organization , Geneva , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Nhat","family":"Linh","sequence":"additional","affiliation":[{"name":"Global Tuberculosis Programme, World Health Organization , Geneva , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel G","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Global Tuberculosis Programme, World Health Organization , Geneva , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Payam","family":"Nahid","sequence":"additional","affiliation":[{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"},{"name":"Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radojka M","family":"Savic","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine , San Francisco, California , USA"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"2023050318400868500_ciac973-B1","volume-title":"WHO operational handbook on tuberculosis. 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