{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:04:03Z","timestamp":1790960643433,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BENEFIT Kids"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Linezolid, a component of rifampicin-resistant\/multidrug-resistant tuberculosis (RR\/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR\/MDR-TB.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated the pharmacokinetics of linezolid and longitudinal hemoglobin data to validate an existing population linezolid pharmacokinetic model. We assessed the impact of linezolid pharmacokinetics and the risk of developing anemia in a prospectively enrolled cohort of children. A previously published population pharmacokinetic linezolid model was validated using nonlinear mixed effects modeling. A multivariable ordinal logistic regression model was built to predict the incidence of anemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 112 children, median age 7.2 years (interquartile range, 2.2\u201316.3), were included from South Africa (n = 87) and India (n = 25). Of these, 24 children contributed new linezolid pharmacokinetic data. The population pharmacokinetic model, which informs the currently recommended linezolid dosing in children (10\u201315 mg\/kg), was validated with these additional new data. For every 1 g\/dL lower baseline hemoglobin level, the odds of developing grade 3 or 4 anemia increased by 2.64 (95% confidence interval [CI], 1.98\u20133.62). For every 1 mg\/L \u00d7 h higher linezolid area under the concentration-time curve, the odds of developing grade 3 or 4 anemia increased by 1.012 (95% CI, 1.007\u20131.017).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Taken together, these data confirm currently recommended linezolid doses for children. The risk of anemia in children should be carefully considered and monitored. Initiating linezolid in children with low baseline hemoglobin increases the probability of experiencing grade 3 or 4 anemia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae497","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T13:00:24Z","timestamp":1729256424000},"page":"1495-1502","source":"Crossref","is-referenced-by-count":3,"title":["Linezolid Pharmacokinetic-Anemia Modeling in Children With Rifampicin-Resistant Tuberculosis"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-9714","authenticated-orcid":false,"given":"Jordan T","family":"Brooks","sequence":"first","affiliation":[{"name":"University of California\u2013San Francisco, Department of Bioengineering and Therapeutics, School of Pharmacy , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-5480","authenticated-orcid":false,"given":"Bel\u00e9n P","family":"Solans","sequence":"additional","affiliation":[{"name":"University of California\u2013San Francisco, Department of Bioengineering and Therapeutics, Schools of Pharmacy and Medicine , San Francisco, California ,","place":["USA"]},{"name":"UCSF Center for Tuberculosis, University of California\u2013San Francisco , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-8249","authenticated-orcid":false,"given":"Agathe","family":"B\u00e9ranger","sequence":"additional","affiliation":[{"name":"University of California\u2013San Francisco, Department of Bioengineering and Therapeutics, Schools of Pharmacy and Medicine , San Francisco, California ,","place":["USA"]},{"name":"UCSF Center for Tuberculosis, University of California\u2013San Francisco , San Francisco, California ,","place":["USA"]},{"name":"URP7323 Pharmacologie et \u00c9valuation des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte, 21 Universit\u00e9 Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-4133","authenticated-orcid":false,"given":"H Simon","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-7477","authenticated-orcid":false,"given":"Louvina","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Institute of Tuberculosis and Respiratory Diseases , New Delhi ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Furin","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather R","family":"Draper","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-9834","authenticated-orcid":false,"given":"Anneke C","family":"Hesseling","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-1950","authenticated-orcid":false,"given":"Anthony J","family":"Garcia-Prats","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, Wisconsin ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radojka M","family":"Savic","sequence":"additional","affiliation":[{"name":"University of California\u2013San Francisco, Department of Bioengineering and Therapeutics, Schools of Pharmacy and Medicine , San Francisco, California ,","place":["USA"]},{"name":"UCSF Center for Tuberculosis, University of California\u2013San Francisco , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"2024121714081564300_ciae497-B1","author":"Azzouz"},{"key":"2024121714081564300_ciae497-B2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1183\/09031936.00191712","article-title":"Linezolid to treat extensively drug-resistant TB: retrospective data are confirmed by experimental evidence","volume":"42","author":"Sotgiu","year":"2013","journal-title":"Eur Respir 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