Hosmann, Arthur and Moser, Miriam M. and van Os, Wisse and Gramms, Leon and al Jalali, Valentin and Codina, Maria Sanz and Ploechl, Walter and Lier, Constantin and Kees, Frieder and Dorn, Christoph and Roessler, Karl and Reinprecht, Andrea and Zeitlinger, Markus (2024) Linezolid brain penetration in neurointensive care patients. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 79 (3). pp. 669-677. ISSN 0305-7453, 1460-2091
Full text not available from this repository. (Request a copy)Abstract
Background: Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown. Objectives: To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients. Patients and methods: Five neurocritical care patients received 600 mg of linezolid IV twice daily for treatment of extracerebral infections. At steady state, blood and CSF samples were collected from arterial and ventricular catheters, and microdialysate was obtained from a cerebral intraparenchymal probe. Results: The median fAUC(0-24) was 57.6 (24.9-365) mg<middle dot>h/L in plasma, 64.1 (43.5-306.1) mg<middle dot>h/L in CSF, and 27.0 (10.7-217.6) mg<middle dot>h/L in cerebral ISF. The median penetration ratio (fAUC(brain_or_CSF)/fAUC(plasma)) was 0.5 (0.25-0.81) for cerebral ISF and 0.92 (0.79-1) for CSF. Cerebral ISF concentrations correlated well with plasma (R = 0.93, P < 0.001) and CSF levels (R = 0.93, P < 0.001). The median fAUC(0-24)/MIC ratio was >= 100 in plasma and CSF for MICs of <= 0.5 mg/L, and in cerebral ISF for MICs of <= 0.25 mg/L. The median fT(>MIC) was >= 80% of the dosing interval in CSF for MICs of <= 0.5 mg/L, and in plasma and cerebral ISF for MICs of <= 0.25 mg/L. Conclusions: Linezolid demonstrates a high degree of cerebral penetration, and brain concentrations correlate well with plasma and CSF levels. However, substantial variability in plasma levels, and thus cerebral concentrations, may result in subtherapeutic tissue concentrations in critically ill patients with standard dosing, necessitating therapeutic drug monitoring.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CEREBROSPINAL-FLUID CONCENTRATIONS; CRITICALLY-ILL PATIENTS; POPULATION PHARMACOKINETICS; EXPERIMENTAL MENINGITIS; PLASMA; PHARMACODYNAMICS; TARGET; SINGLE |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 10:34 |
| Last Modified: | 22 Jan 2026 10:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64203 |
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