{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:39:49Z","timestamp":1791725989943,"version":"4.3.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43 TW007124"],"award-info":[{"award-number":["D43 TW007124"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R03 AI139871"],"award-info":[{"award-number":["R03 AI139871"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23AI103044"],"award-info":[{"award-number":["K23AI103044"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23 AI144040"],"award-info":[{"award-number":["K23 AI144040"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["TL1TR002382"],"award-info":[{"award-number":["TL1TR002382"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The ability of antituberculosis drugs to cross the blood\u2013brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 \u00b5g\/mL with adjusted CSF\/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 \u00b5g\/mL at 2 and 6 hours, with adjusted CSF\/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab992","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T20:16:50Z","timestamp":1637871410000},"page":"682-689","source":"Crossref","is-referenced-by-count":46,"title":["Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-4996","authenticated-orcid":false,"given":"Russell R","family":"Kempker","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison G C","family":"Smith","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teona","family":"Avaliani","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Gujabidze","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinatin","family":"Bakuradze","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Sabanadze","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaza","family":"Avaliani","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad H","family":"Alshaer","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida , Gainesville, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Peloquin","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida , Gainesville, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Kipiani","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases , Tbilisi , Georgia"},{"name":"The University of Georgia , Tbilisi , Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"2022091018191297000_CIT0001","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nrneurol.2017.120","article-title":"Tuberculous meningitis.","volume":"13","author":"Wilkinson","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"2022091018191297000_CIT0002","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.tube.2010.07.002","article-title":"Cerebrospinal fluid concentrations of antituberculosis agents in adults and children.","volume":"90","author":"Donald","year":"2010","journal-title":"Tuberculosis (Edinb)"},{"key":"2022091018191297000_CIT0003","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/cid\/cix230","article-title":"Clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis 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