{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:16:34Z","timestamp":1764688594421,"version":"3.46.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Degree & Postgraduate Education Reform Project of Central South University","award":["2023JGB123","2024JGB061"],"award-info":[{"award-number":["2023JGB123","2024JGB061"]}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for the Central Universities of Central South University","doi-asserted-by":"publisher","award":["2022XQLH154"],"award-info":[{"award-number":["2022XQLH154"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pfizer\u2019s Global Medical Grants Program","award":["99106247"],"award-info":[{"award-number":["99106247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose significant therapeutic challenges, primarily due to the limited penetration of antimicrobial agents across the blood-brain barrier. Ceftazidime\/avibactam demonstrates efficacy against multidrug-resistant Gram-negative pathogens. However, its CSF pharmacokinetics and optimal dosing in patients with augmented renal clearance (ARC; CrCl\u200a&amp;gt;\u200a130\u2005mL\/min\/1.73\u2005m\u00b2) remain inadequately characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized validated high-performance liquid chromatography to quantify ceftazidime\/avibactam concentrations in paired plasma and CSF samples obtained from a traumatic brain injury patient with CRKP ventriculitis and ARC (CrCl 154.37\u2005mL\/min\/1.73\u2005m\u00b2). The MIC of ceftazidime\/avibactam was determined using broth microdilution in accordance with Clinical and Laboratory Standards Institute guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Standard Ceftazidime\/avibactam dosing (2.5\u2005g q8h) resulted in subtherapeutic trough concentrations in both plasma (ceftazidime\/avibactam: 10.39\/0.96\u2005\u00b5g\/mL) and CSF (ceftazidime\/avibactam: 20.4\/0.68\u2005\u00b5g\/mL) against the target pathogen (MIC\u200a=\u200a4\u2005mg\/L). Dose intensification to 2.5\u2005g q6h administered via 3-h prolonged infusion achieved supra-therapeutic exposures (troughs: plasma 65.60\/8.70\u2005\u00b5g\/mL; CSF 58.90\/10.82\u2005\u00b5g\/mL; CSF\/plasma ratio\u200a=\u200a0.9 for ceftazidime), which correlated with CSF sterilization and resolution of inflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This first-in-human pharmacokinetic evidence in a patient with ARC underscores the inadequacy of conventional ceftazidime\/avibactam regimens in this population. Our findings advocate for therapeutic drug monitoring-guided dose optimization incorporating extended infusions to achieve therapeutic targets. These results emphasize the critical need for personalized dosing algorithms in the neurocritical care setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jacamr\/dlaf206","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:56:38Z","timestamp":1762865798000},"source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid and plasma pharmacokinetics of ceftazidime\/avibactam in a neurocritical patient with CRKP intracranial infection and augmented renal clearance"],"prefix":"10.1093","volume":"7","author":[{"given":"Si-Min","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Second Xiangya Hospital, Central South University , Changsha 410011 ,","place":["China"]},{"name":"Institute of Clinical Pharmacy, Central South University , Changsha 410011 ,","place":["China"]},{"name":"Department of Pharmacy, Foresea Life Insurance Shaoguan Hospital , Shaoguan 512000 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