{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:13:04Z","timestamp":1774627984931,"version":"3.50.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1007\/s13318-025-00981-0","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:50:52Z","timestamp":1770288652000},"page":"193-204","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining Safe and Effective Cefazolin Dosing Regimens for MSSA Infections in the CNS: Leveraging Sparse Real-World Data and PBPK Modeling"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-4899","authenticated-orcid":false,"given":"Samuel","family":"Dubinsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"McIntyre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Hawryluk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Edginton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"issue":"3","key":"981_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ijantimicag.2015.12.009","volume":"47","author":"R Chew","year":"2016","unstructured":"Chew R, Woods ML. Flucloxacillin does not achieve therapeutic cerebrospinal fluid levels against meticillin-sensitive Staphylococcus aureus in adults: a case report and review of the literature. Int J Antimicrob Agents. 2016;47(3):229\u201331. https:\/\/doi.org\/10.1016\/j.ijantimicag.2015.12.009.","journal-title":"Int J Antimicrob Agents"},{"issue":"10","key":"981_CR2","doi-asserted-by":"publisher","first-page":"1415.e1","DOI":"10.1016\/j.cmi.2020.04.046","volume":"26","author":"P Le Turnier","year":"2020","unstructured":"Le Turnier P, Gregoire M, Deslandes G, et\u00a0al. Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis. Clin Microbiol Infect. 2020;26(10):1415.e1-1415.e4. https:\/\/doi.org\/10.1016\/j.cmi.2020.04.046.","journal-title":"Clin Microbiol Infect"},{"issue":"6","key":"981_CR3","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/cid\/ciw861","volume":"64","author":"AR Tunkel","year":"2017","unstructured":"Tunkel AR, Hasbun R, Bhimraj A, et\u00a0al. 2017 Infectious Diseases Society of America\u2019s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64(6):e34\u201365. https:\/\/doi.org\/10.1093\/cid\/ciw861.","journal-title":"Clin Infect Dis"},{"issue":"9","key":"981_CR4","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1086\/425368","volume":"39","author":"AR Tunkel","year":"2004","unstructured":"Tunkel AR, Hartman BJ, Kaplan SL, et\u00a0al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267\u201384. https:\/\/doi.org\/10.1086\/425368.","journal-title":"Clin Infect Dis"},{"issue":"1","key":"981_CR5","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1186\/s12879-018-3418-9","volume":"18","author":"C Shi","year":"2018","unstructured":"Shi C, Xiao Y, Zhang Q, et\u00a0al. Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis. BMC Infect Dis. 2018;18(1):508. https:\/\/doi.org\/10.1186\/s12879-018-3418-9.","journal-title":"BMC Infect Dis"},{"issue":"7","key":"981_CR6","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.cmi.2020.08.044","volume":"27","author":"R Lecomte","year":"2021","unstructured":"Lecomte R, Bourreau A, Deschanvres C, et\u00a0al. Comparative outcomes of cefazolin versus antistaphylococcal penicillins in methicillin-susceptible Staphylococcus aureus infective endocarditis: a post hoc analysis of a prospective multicentre French cohort study. Clin Microbiol Infect. 2021;27(7):1015\u201321. https:\/\/doi.org\/10.1016\/j.cmi.2020.08.044.","journal-title":"Clin Microbiol Infect"},{"issue":"4","key":"981_CR7","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01816-17","volume":"62","author":"K Eljaaly","year":"2018","unstructured":"Eljaaly K, Alshehri S, Erstad BL. Systematic review and meta-analysis of the safety of antistaphylococcal penicillins compared to cefazolin. Antimicrob Agents Chemother. 2018;62(4):e01816-17. https:\/\/doi.org\/10.1128\/AAC.01816-17.","journal-title":"Antimicrob Agents Chemother"},{"issue":"8","key":"981_CR8","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1007\/s10096-024-04851-6","volume":"43","author":"AL Destrem","year":"2024","unstructured":"Destrem AL, Maillard A, Simonet M, et\u00a0al. Effectiveness and safety of cefazolin versus cloxacillin in endocarditis due to methicillin-susceptible Staphylococcus spp.: a multicenter propensity weighted cohort study. Eur J Clin Microbiol Infect Dis. 2024;43(8):1569\u201377. https:\/\/doi.org\/10.1007\/s10096-024-04851-6.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"3","key":"981_CR9","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/cid\/civ308","volume":"61","author":"JS McDanel","year":"2015","unstructured":"McDanel JS, Perencevich EN, Diekema DJ, et\u00a0al. Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis. 2015;61(3):361\u20137. https:\/\/doi.org\/10.1093\/cid\/civ308.","journal-title":"Clin Infect Dis"},{"issue":"2","key":"981_CR10","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01844-18","volume":"63","author":"M Gr\u00e9goire","year":"2019","unstructured":"Gr\u00e9goire M, Gaborit B, Deschanvres C, et\u00a0al. High-dosage cefazolin achieves sufficient cerebrospinal diffusion to treat an external ventricular drainage-related Staphylococcus aureus ventriculitis. Antimicrob Agents Chemother. 2019;63(2):e01844-18. https:\/\/doi.org\/10.1128\/AAC.01844-18.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"981_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10143-002-0224-y","volume":"26","author":"D Kreppel","year":"2003","unstructured":"Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurg Rev. 2003;26(1):1\u201349. https:\/\/doi.org\/10.1007\/s10143-002-0224-y.","journal-title":"Neurosurg Rev"},{"issue":"5","key":"981_CR12","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.3171\/2011.6.JNS11167","volume":"115","author":"TA Williams","year":"2011","unstructured":"Williams TA, Leslie GD, Dobb GJ, Roberts B, van Heerden PV. Decrease in proven ventriculitis by reducing the frequency of cerebrospinal fluid sampling from extraventricular drains. J Neurosurg. 2011;115(5):1040\u20136. https:\/\/doi.org\/10.3171\/2011.6.JNS11167.","journal-title":"J Neurosurg"},{"issue":"7","key":"981_CR13","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/psp4.12414","volume":"8","author":"JG Gerhart","year":"2019","unstructured":"Gerhart JG, Watt KM, Edginton A, et\u00a0al. Physiologically-based pharmacokinetic modeling of fluconazole using plasma and cerebrospinal fluid samples from preterm and term infants. CPT Pharmacomet Syst Pharmacol. 2019;8(7):500\u201310. https:\/\/doi.org\/10.1002\/psp4.12414.","journal-title":"CPT Pharmacomet Syst Pharmacol"},{"issue":"2","key":"981_CR14","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/cts.12517","volume":"11","author":"AN Edginton","year":"2018","unstructured":"Edginton AN. Using physiologically based pharmacokinetic modeling for mechanistic insight: cases of reverse translation. Clin Transl Sci. 2018;11(2):109\u201311. https:\/\/doi.org\/10.1111\/cts.12517.","journal-title":"Clin Transl Sci"},{"key":"981_CR15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1146\/annurev-pharmtox-010510-100540","volume":"51","author":"M Rowland","year":"2011","unstructured":"Rowland M, Peck C, Tucker G. Physiologically-based pharmacokinetics in drug development and regulatory science. Annu Rev Pharmacol Toxicol. 2011;51:45\u201373. https:\/\/doi.org\/10.1146\/annurev-pharmtox-010510-100540.","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"12","key":"981_CR16","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1007\/s40262-016-0422-3","volume":"55","author":"JF Schlender","year":"2016","unstructured":"Schlender JF, Meyer M, Thelen K, et\u00a0al. Development of a whole-body physiologically based pharmacokinetic approach to assess the pharmacokinetics of drugs in elderly individuals. Clin Pharmacokinet. 2016;55(12):1573\u201389. https:\/\/doi.org\/10.1007\/s40262-016-0422-3.","journal-title":"Clin Pharmacokinet"},{"issue":"3","key":"981_CR17","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10928-007-9053-5","volume":"34","author":"S Willmann","year":"2007","unstructured":"Willmann S, H\u00f6hn K, Edginton A, et\u00a0al. Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs. J Pharmacokinet Pharmacodyn. 2007;34(3):401\u201331. https:\/\/doi.org\/10.1007\/s10928-007-9053-5.","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"12","key":"981_CR18","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1007\/s40262-017-0538-0","volume":"56","author":"A Dallmann","year":"2017","unstructured":"Dallmann A, Ince I, Solodenko J, et\u00a0al. Physiologically based pharmacokinetic modeling of renally cleared drugs in pregnant women. Clin Pharmacokinet. 2017;56(12):1525\u201341. https:\/\/doi.org\/10.1007\/s40262-017-0538-0.","journal-title":"Clin Pharmacokinet"},{"issue":"11","key":"981_CR19","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1002\/psp4.12250","volume":"6","author":"Y Yamamoto","year":"2017","unstructured":"Yamamoto Y, V\u00e4litalo PA, Huntjens DR, et\u00a0al. Predicting drug concentration-time profiles in multiple CNS compartments using a comprehensive physiologically-based pharmacokinetic model. CPT Pharmacomet Syst Pharmacol. 2017;6(11):765\u201377. https:\/\/doi.org\/10.1002\/psp4.12250.","journal-title":"CPT Pharmacomet Syst Pharmacol"},{"issue":"5","key":"981_CR20","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s10928-021-09768-7","volume":"48","author":"MAA Saleh","year":"2021","unstructured":"Saleh MAA, Loo CF, Elassaiss-Schaap J, De Lange ECM. Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations. J Pharmacokinet Pharmacodyn. 2021;48(5):725\u201341. https:\/\/doi.org\/10.1007\/s10928-021-09768-7.","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"2","key":"981_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab649","volume":"9","author":"AR Novak","year":"2022","unstructured":"Novak AR, Krsak M, Kiser TH, et\u00a0al. Pharmacokinetic evaluation of cefazolin in the cerebrospinal fluid of critically ill patients. Open Forum Infect Dis. 2022;9(2):ofab649. https:\/\/doi.org\/10.1093\/ofid\/ofab649.","journal-title":"Open Forum Infect Dis"},{"issue":"4","key":"981_CR22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrmicro862","volume":"2","author":"GL Drusano","year":"2004","unstructured":"Drusano GL. Antimicrobial pharmacodynamics: critical interactions of \u201cbug and drug.\u201d Nat Rev Microbiol. 2004;2(4):289\u2013300. https:\/\/doi.org\/10.1038\/nrmicro862.","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"981_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/516284","volume":"26","author":"WA Craig","year":"1998","unstructured":"Craig WA. Pharmacokinetic\/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis Off Publ Infect Dis Soc Am. 1998;26(1):1\u201310. https:\/\/doi.org\/10.1086\/516284.","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"1-2","key":"981_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0732-8893(95)00053-d","volume":"22","author":"WA Craig","year":"1995","unstructured":"Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995;22(1\u20132):89\u201396. https:\/\/doi.org\/10.1016\/0732-8893(95)00053-d.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"8","key":"981_CR25","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1093\/cid\/ciu027","volume":"58","author":"JA Roberts","year":"2014","unstructured":"Roberts JA, Paul SK, Akova M, et\u00a0al. DALI: defining antibiotic levels in intensive care unit patients: are current \u03b2-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072\u201383. https:\/\/doi.org\/10.1093\/cid\/ciu027.","journal-title":"Clin Infect Dis"},{"issue":"9","key":"981_CR26","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1093\/cid\/ciu043","volume":"58","author":"JD Bard","year":"2014","unstructured":"Bard JD, Hindler JA, Gold HS, Limbago B. Rationale for eliminating Staphylococcus breakpoints for \u03b2-lactam agents other than penicillin, oxacillin or cefoxitin, and ceftaroline. Clin Infect Dis. 2014;58(9):1287\u201396. https:\/\/doi.org\/10.1093\/cid\/ciu043.","journal-title":"Clin Infect Dis"},{"key":"981_CR27","unstructured":"The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 10.0; 2020. Accessed October 2024."},{"issue":"5","key":"981_CR28","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1177\/106002807801200501","volume":"12","author":"ME Gardner","year":"1978","unstructured":"Gardner ME, Fritz WL, Hyland RN. A case attributed to Cefazolin and a review of the literature. Drug Intell Clin Pharm. 1978;12(5):268\u201371. https:\/\/doi.org\/10.1177\/106002807801200501.","journal-title":"Drug Intell Clin Pharm"},{"issue":"10","key":"981_CR29","first-page":"1496","volume":"38","author":"TD Moore","year":"1981","unstructured":"Moore TD, Bechtel TP, Ayers LW. Effect of multidose therapy on cerebrospinal fluid penetration of cefazolin. Am J Hosp Pharm. 1981;38(10):1496\u20139.","journal-title":"Am J Hosp Pharm"},{"issue":"2","key":"981_CR30","first-page":"271","volume":"37","author":"TP Bechtel","year":"1980","unstructured":"Bechtel TP, Slaughter RL, Moore TD. Seizures associated with high cerebrospinal fluid concentrations of cefazolin. Am J Hosp Pharm. 1980;37(2):271\u20133.","journal-title":"Am J Hosp Pharm"},{"issue":"5","key":"981_CR31","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1128\/AAC.16.5.615","volume":"16","author":"RD Smyth","year":"1979","unstructured":"Smyth RD, Pfeffer M, Glick A, Van Harken DR, Hottendorf GH. Clinical pharmacokinetics and safety of high doses of ceforanide (BL-S786R) and cefazolin. Antimicrob Agents Chemother. 1979;16(5):615\u201321. https:\/\/doi.org\/10.1128\/AAC.16.5.615.","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"981_CR32","doi-asserted-by":"publisher","first-page":"136","DOI":"10.2165\/00003088-198712020-00004","volume":"12","author":"A Philipson","year":"1987","unstructured":"Philipson A, Stiernstedt G, Ehrnebo M. Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women. Clin Pharmacokinet. 1987;12(2):136\u201344. https:\/\/doi.org\/10.2165\/00003088-198712020-00004.","journal-title":"Clin Pharmacokinet"},{"issue":"18","key":"981_CR33","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1056\/NEJMoa040845","volume":"351","author":"D van de Beek","year":"2004","unstructured":"van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004;351(18):1849\u201359. https:\/\/doi.org\/10.1056\/NEJMoa040845.","journal-title":"N Engl J Med"},{"issue":"1","key":"981_CR34","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/0022-510x(94)90052-3","volume":"122","author":"R Nau","year":"1994","unstructured":"Nau R, S\u00f6rgel F, Prange HW. Lipophilicity at pH 7.4 and molecular size govern the entry of the free serum fraction of drugs into the cerebrospinal fluid in humans with uninflamed meninges. J Neurol Sci. 1994;122(1):61\u20135. https:\/\/doi.org\/10.1016\/0022-510x(94)90052-3.","journal-title":"J Neurol Sci"},{"issue":"4","key":"981_CR35","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1128\/CMR.00007-10","volume":"23","author":"R Nau","year":"2010","unstructured":"Nau R, S\u00f6rgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid\/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 2010;23(4):858\u201383. https:\/\/doi.org\/10.1128\/CMR.00007-10.","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"981_CR36","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/phar.2750","volume":"43","author":"K Antosz","year":"2023","unstructured":"Antosz K, Battle S, Chang J, Scheetz MH, Al-Hasan M, Bookstaver PB. Cefazolin in the treatment of central nervous system infections: a narrative review and recommendation. Pharmacotherapy. 2023;43(1):85\u201395. https:\/\/doi.org\/10.1002\/phar.2750.","journal-title":"Pharmacotherapy"},{"issue":"8","key":"981_CR37","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s40262-017-0506-8","volume":"56","author":"A Ivanyuk","year":"2017","unstructured":"Ivanyuk A, Livio F, Biollaz J, Buclin T. Renal drug transporters and drug interactions. Clin Pharmacokinet. 2017;56(8):825\u201392. https:\/\/doi.org\/10.1007\/s40262-017-0506-8.","journal-title":"Clin Pharmacokinet"},{"issue":"2","key":"981_CR38","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1111\/j.1471-4159.2011.07208.x","volume":"117","author":"Y Uchida","year":"2011","unstructured":"Uchida Y, Ohtsuki S, Katsukura Y, et\u00a0al. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors. J Neurochem. 2011;117(2):333\u201345. https:\/\/doi.org\/10.1111\/j.1471-4159.2011.07208.x.","journal-title":"J Neurochem"},{"issue":"5","key":"981_CR39","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1021\/mp300518e","volume":"10","author":"N Strazielle","year":"2013","unstructured":"Strazielle N, Ghersi-Egea JF. Physiology of blood\u2013brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm. 2013;10(5):1473\u201391. https:\/\/doi.org\/10.1021\/mp300518e.","journal-title":"Mol Pharm"},{"issue":"4","key":"981_CR40","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1021\/mp200129p","volume":"8","author":"R Shawahna","year":"2011","unstructured":"Shawahna R, Uchida Y, Decl\u00e8ves X, et\u00a0al. Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Mol Pharm. 2011;8(4):1332\u201341. https:\/\/doi.org\/10.1021\/mp200129p.","journal-title":"Mol Pharm"},{"issue":"2","key":"981_CR41","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1227\/00006123-198302000-00002","volume":"12","author":"PT Frame","year":"1983","unstructured":"Frame PT, Watanakunakorn C, McLaurin RL, Khodadad G. Penetration of nafcillin, methicillin, and cefazolin into human brain tissue. Neurosurgery. 1983;12(2):142\u20137. https:\/\/doi.org\/10.1227\/00006123-198302000-00002.","journal-title":"Neurosurgery"},{"issue":"3","key":"981_CR42","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2217\/fmb.12.1","volume":"7","author":"NM van Sorge","year":"2012","unstructured":"van Sorge NM, Doran KS. Defense at the border: the blood-brain barrier versus bacterial foreigners. Future Microbiol. 2012;7(3):383\u201394. https:\/\/doi.org\/10.2217\/fmb.12.1.","journal-title":"Future Microbiol"},{"issue":"1","key":"981_CR43","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1006\/exnr.1997.6458","volume":"145","author":"KS Kim","year":"1997","unstructured":"Kim KS, Wass CA, Cross AS. Blood\u2013brain barrier permeability during the development of experimental bacterial meningitis in the rat. Exp Neurol. 1997;145(1):253\u20137. https:\/\/doi.org\/10.1006\/exnr.1997.6458.","journal-title":"Exp Neurol"},{"issue":"3","key":"981_CR44","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1084\/jem.174.3.657","volume":"174","author":"VJ Quagliarello","year":"1991","unstructured":"Quagliarello VJ, Ma A, Stukenbrok H, Palade GE. Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. J Exp Med. 1991;174(3):657\u201372. https:\/\/doi.org\/10.1084\/jem.174.3.657.","journal-title":"J Exp Med"},{"issue":"4","key":"981_CR45","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1128\/AAC.6.4.437","volume":"6","author":"RG Dacey","year":"1974","unstructured":"Dacey RG, Sande MA. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1974;6(4):437\u201341. https:\/\/doi.org\/10.1128\/AAC.6.4.437.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"981_CR46","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1471-4159.2009.06305.x","volume":"111","author":"M von Wedel-Parlow","year":"2009","unstructured":"von Wedel-Parlow M, W\u00f6lte P, Galla HJ. Regulation of major efflux transporters under inflammatory conditions at the blood-brain barrier in vitro. J Neurochem. 2009;111(1):111\u20138. https:\/\/doi.org\/10.1111\/j.1471-4159.2009.06305.x.","journal-title":"J Neurochem"},{"issue":"1","key":"981_CR47","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1097\/QCO.0000000000000418","volume":"31","author":"R Nau","year":"2018","unstructured":"Nau R, Seele J, Djukic M, Eiffert H. Pharmacokinetics and pharmacodynamics of antibiotics in central nervous system infections. Curr Opin Infect Dis. 2018;31(1):57\u201368. https:\/\/doi.org\/10.1097\/QCO.0000000000000418.","journal-title":"Curr Opin Infect Dis"},{"issue":"4","key":"981_CR48","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/s0733-8619(05)70171-7","volume":"17","author":"BP Kearney","year":"1999","unstructured":"Kearney BP, Aweeka FT. The penetration of anti-infectives into the central nervous system. Neurol Clin. 1999;17(4):883\u2013900. https:\/\/doi.org\/10.1016\/s0733-8619(05)70171-7.","journal-title":"Neurol Clin"},{"issue":"9","key":"981_CR49","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00451-24","volume":"68","author":"SG Wicha","year":"2024","unstructured":"Wicha SG, Kinast C, M\u00fcnchow M, et\u00a0al. Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill patients\u2014A prospective cohort study. Antimicrob Agents Chemother. 2024;68(9):e00451-24. https:\/\/doi.org\/10.1128\/aac.00451-24.","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"981_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/cc10441","volume":"15","author":"J Gon\u00e7alves-Pereira","year":"2011","unstructured":"Gon\u00e7alves-Pereira J, P\u00f3voa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of \u03b2-lactams. Crit Care. 2011;15(5):R206. https:\/\/doi.org\/10.1186\/cc10441.","journal-title":"Crit Care"},{"issue":"4","key":"981_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/cc9091","volume":"14","author":"FS Taccone","year":"2010","unstructured":"Taccone FS, Laterre PF, Dugernier T, et\u00a0al. Insufficient \u03b2-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. https:\/\/doi.org\/10.1186\/cc9091.","journal-title":"Crit Care"},{"issue":"3","key":"981_CR52","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1097\/CCM.0b013e3181968e44","volume":"37","author":"JA Roberts","year":"2009","unstructured":"Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis\u2014Bolus versus continuous administration? Crit Care Med. 2009;37(3):926\u201333. https:\/\/doi.org\/10.1097\/CCM.0b013e3181968e44.","journal-title":"Crit Care Med"},{"issue":"5","key":"981_CR53","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1086\/515003","volume":"27","author":"I Lutsar","year":"1998","unstructured":"Lutsar I, McCracken GH, Friedland IR. Antibiotic pharmacodynamics in cerebrospinal fluid. Clin Infect Dis Off Publ Infect Dis Soc Am. 1998;27(5):1117\u201327. https:\/\/doi.org\/10.1086\/515003.","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"1","key":"981_CR54","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ijantimicag.2013.08.019","volume":"43","author":"H Huang","year":"2014","unstructured":"Huang H, Huang S, Zhu P, Xi X. Continuous versus intermittent infusion of cefepime in neurosurgical patients with post-operative intracranial infections. Int J Antimicrob Agents. 2014;43(1):68\u201372. https:\/\/doi.org\/10.1016\/j.ijantimicag.2013.08.019.","journal-title":"Int J Antimicrob Agents"},{"issue":"3","key":"981_CR55","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/s0028-3908(03)00188-6","volume":"45","author":"M Sugimoto","year":"2003","unstructured":"Sugimoto M, Uchida I, Mashimo T, et\u00a0al. Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins. Neuropharmacology. 2003;45(3):304\u201314. https:\/\/doi.org\/10.1016\/s0028-3908(03)00188-6.","journal-title":"Neuropharmacology"},{"issue":"9","key":"981_CR56","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1111\/j.1528-1167.2005.16305.x","volume":"46","author":"JL Fern\u00e1ndez-Torre","year":"2005","unstructured":"Fern\u00e1ndez-Torre JL, Mart\u00ednez-Mart\u00ednez M, Gonz\u00e1lez-Rato J, et\u00a0al. Cephalosporin-induced nonconvulsive status epilepticus: clinical and electroencephalographic features. Epilepsia. 2005;46(9):1550\u20132. https:\/\/doi.org\/10.1111\/j.1528-1167.2005.16305.x.","journal-title":"Epilepsia"},{"issue":"3","key":"981_CR57","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1084\/jem.174.3.657","volume":"174","author":"VJ Quagliarello","year":"1991","unstructured":"Quagliarello VJ, Ma A, Stukenbrok H, Palade GE. Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. J Exp Med. 1991;174(3):657\u201372.","journal-title":"J Exp Med"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-025-00981-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13318-025-00981-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-025-00981-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:23:51Z","timestamp":1774625031000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13318-025-00981-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["981"],"URL":"https:\/\/doi.org\/10.1007\/s13318-025-00981-0","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"value":"0378-7966","type":"print"},{"value":"2107-0180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]},"assertion":[{"value":"21 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SD, MM, MK, LH, AE report no conflicts of interests","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest\/Competing Interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The datasets used for model development and\/or evaluation, including PBPK model files are available from the corresponding author upon reasonable request.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"The model codes that support the findings of this study are available upon reasonable request.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"SD, MM, and AE conceptualized the idea and topic of this study. With assistance from MK, SD performed PBPK modelling for cefazolin that was presented throughout this manuscript. Review and input on PBPK modelling strategies was conducted by AE. Writing, review and editing was performed by SD, MM, MK, LH, and AE.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}