{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:35:13Z","timestamp":1787312113611,"version":"build-2736575974"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"University of Munich LMU","award":["F\u00f6FoLe No. 002"],"award-info":[{"award-number":["F\u00f6FoLe No. 002"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Meropenem penetration into the cerebrospinal fluid (CSF) is subject to high interindividual variability resulting in uncertain target attainment in CSF. Recently, several authors recommended administering meropenem as a continuous infusion (CI) to optimize CSF exposure. This study aimed to compare the concentrations and pharmacokinetics of meropenem in CSF after intermittent infusion (II) and CI. This prospective, observational study (NCT04426383) included critically ill patients with external ventricular drains who received either II or CI of meropenem. Meropenem pharmacokinetics in plasma and CSF were characterized using population pharmacokinetic modeling (NONMEM 7.5). The developed model was used to compare the concentration\u2013time profile and probability of target attainment (PTA) between II and CI. A total of 16 patients (8 CI, 8 II; samples: n\n                      <jats:sub>plasma<\/jats:sub>\n                      = 243, n\n                      <jats:sub>CSF<\/jats:sub>\n                      = 263) were recruited, with nine patients (5 CI, 4 II) suffering from cerebral and seven patients from extracerebral infections. A one-compartment model described the plasma concentrations adequately. Meropenem penetration into the CSF (partition coefficient (KP), c\n                      <jats:sub>CSF<\/jats:sub>\n                      \/c\n                      <jats:sub>plasma<\/jats:sub>\n                      ) was generally low (6.0%), exhibiting substantial between-subject variability (coefficient of variation: 84.0%). There was no correlation between the infusion mode and KP, but interleukin (IL)-6 measured in CSF showed a strong positive correlation with KP (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Dosing simulations revealed no relevant differences in CSF concentrations and PTA in CSF between CI and II. Our study did not demonstrate increased penetration rates or higher concentrations of meropenem in the CSF with CI compared with II.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CLINICAL TRIALS<\/jats:title>\n                    <jats:p>\n                      This study is registered with\n                      <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"pre-results\" document-id=\"NCT04426383\" document-id-type=\"clinical-trial-number\" source-id=\"http:\/\/clinicaltrials.gov\/\" source-id-type=\"registry-nameov\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/show\/NCT04426383\">\n                        <jats:ext-link ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link>\n                        as\n                        <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04426383\" xlink:type=\"simple\">NCT04426383<\/jats:ext-link>\n                      <\/jats:related-object>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00451-24","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T09:00:53Z","timestamp":1722416453000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill patients\u2014a prospective cohort study"],"prefix":"10.1128","volume":"68","author":[{"given":"Sebastian G.","family":"Wicha","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kinast","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"M\u00fcnchow","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Wittova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Greppmair","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, 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