{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:49Z","timestamp":1785420169637,"version":"3.56.0"},"reference-count":12,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Beijing Municipal Health Commission Excellent Clinical Research Program for Research-Oriented Wards","award":["BRWEP2024W042160104 and BRWEP2024W042160109"],"award-info":[{"award-number":["BRWEP2024W042160104 and BRWEP2024W042160109"]}]},{"name":"Beijing Municipal Health Commission Dengfeng Program","award":["G202511062"],"award-info":[{"award-number":["G202511062"]}]},{"name":"the Beijing Tongzhou District Science and Technology Program Project","award":["WS2024017"],"award-info":[{"award-number":["WS2024017"]}]},{"name":"Guangzhou National Laboratory 2024 Special Project on Tuberculosis Short-Course Therapy","award":["GZNL2024A01030"],"award-info":[{"award-number":["GZNL2024A01030"]}]},{"name":"Tongzhou District Health Development Research Reserve Program, Tongzhou District Commission of Science and Technology of Beijing Municipality of China","award":["KJ2023CX048"],"award-info":[{"award-number":["KJ2023CX048"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) with high mortality. This study evaluated the cerebrospinal fluid (CSF) concentration and safety of the novel oxazolidinone contezolid compared to linezolid in TBM patients. In this randomized prospective study, 10 TBM patients received either a linezolid-containing (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5) or contezolid-containing (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5) anti-TB regimen. CSF and blood concentrations were measured at 2 and 6 h post-dose. Peak (2 h) and trough (6 h) concentrations, area under the concentration-time curve (AUC), and safety were assessed. Contezolid CSF concentrations exceeded the\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb) MIC (0.5 \u03bcg\/mL) at 2 h (median: 1.0806 \u03bcg\/mL, range: 0.9295\u20131.3165 \u03bcg\/mL) but declined by 6 h (median: 0.7920 \u03bcg\/mL, range: 0.1867\u20131.0194 \u03bcg\/mL). Linezolid CSF concentrations were significantly higher than contezolid at both 2 h (median: 3.251 \u03bcg\/mL, range: 1.9545\u20134.9636 \u03bcg\/mL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.008) and 6 h (median: 1.623 \u03bcg\/mL, range: 0.941\u20131.765 \u03bcg\/mL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016), remaining above MIC in all samples at 6 h. The mean CSF AUC for contezolid (4.637 \u03bcg\u00b7h\/mL, 95% CI: 3.599\u20135.675) was significantly lower than that for linezolid (12.537 \u03bcg\u00b7h\/mL, 95% CI: 7.8797\u201317.277;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.008). Blood concentrations were higher than CSF for both drugs at all time points. No serious drug-related adverse events occurred. Contezolid effectively penetrates the blood-CSF barrier in TBM patients, achieving CSF concentrations above the MIC for Mtb. Although its CSF exposure was significantly lower than linezolid, its demonstrated penetration and safety profile suggest contezolid warrants further investigation as a potential treatment option for drug-resistant TBM.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Tuberculous meningitis (TBM) is the deadliest form of tuberculosis, especially difficult-to-treat drug-resistant TBM. Finding new, effective, and safe medicines is critical. This study provides evidence in TBM patients that a newer antibiotic, contezolid, successfully reaches the infection site in cerebrospinal fluid (CSF) at levels expected to kill\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        . While linezolid achieved higher levels in CSF, contezolid still reached concentrations predicted to be effective and caused no serious side effects in our study. This is important because contezolid might offer a safer alternative to linezolid, which can have significant long-term toxicity. These promising results suggest contezolid could become a valuable new weapon against refractory drug-resistant TBM, potentially saving lives where current options are limited or too toxic.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02399-25","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:40:25Z","timestamp":1773409225000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of contezolid\u2019s cerebrospinal fluid concentration and safety in tuberculous meningitis patients"],"prefix":"10.1128","volume":"14","author":[{"given":"Mailing","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-1884","authenticated-orcid":true,"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Drug Research Laboratory, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-1705","authenticated-orcid":false,"given":"Naihui","family":"Chu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1109-1983","authenticated-orcid":true,"given":"Wenjuan","family":"Nie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2025 Global tuberculosis report 2024. Geneva[EB\/OL]. Available from: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldv003"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2208554"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S425743"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70138-9"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1224179"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15573.1"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02784-14"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06705-4"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2022.01025"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2023.106875"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1224179"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02399-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02399-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:07:34Z","timestamp":1775567254000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02399-25"}},"subtitle":[],"editor":[{"given":"Monika","family":"Kumaraswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,7]]}},"alternative-id":["10.1128\/spectrum.02399-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02399-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2025-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02399-25"}}