Chen, Zhendong and Taubert, Max and Chen, Chunli and Dokos, Charalambos and Fuhr, Uwe and Weig, Thomas and Zoller, Michael and Heck, Suzette and Dimitriadis, Konstantinos and Terpolilli, Nicole and Kinast, Christina and Scharf, Christina and Lier, Constantin and Dorn, Christoph and Liebchen, Uwe (2023) Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 67 (6). ISSN 0066-4804, 1098-6596
Full text not available from this repository. (Request a copy)Abstract
Vancomycin is a commonly used antibacterial agent in patients with primary central nervous system (CNS) infection. This study aims to examine predictors of vancomycin penetration into cerebrospinal fluid (CSF) in patients with external ventricular drainage and the feasibility of CSF sampling from the distal drainage port for therapeutic drug monitoring. Fourteen adult patients (9 with primary CNS infection) were treated with vancomycin intravenously. The vancomycin concentrations in blood and CSF (from proximal [CSF_P] and distal [CSF_D] drainage ports) were evaluated by population pharmacokinetics. Model-based simulations were conducted to compare various infusion modes. A three-compartment model with first-order elimination best described the vancomycin data. Estimated parameters included clearance (CL, 4.53 L/h), central compartment volume (V-c, 24.0 L), apparent CSF compartment volume (V-CSF, 0.445 L), and clearance between central and CSF compartments (Q(CSF), 0.00322 L/h and 0.00135 L/h for patients with and without primary CNS infection, respectively). Creatinine clearance was a significant covariate on vancomycin CL. CSF protein was the primary covariate to explain the variability of Q(CSF). There was no detectable difference between the data for sampling from the proximal and the distal port. Intermittent infusion and continuous infusion with a loading dose reached the CSF target concentration faster than continuous infusion only. All infusion schedules reached similar CSF trough concentrations. Beyond adjusting doses according to renal function, starting treatment with a loading dose in patients with primary CSF infection is recommended. Occasionally, very high and possibly toxic doses would be required to achieve adequate CSF concentrations, which calls for more investigation of direct intraventricular administration of vancomycin. (This study has been registered at ClinicalTrials.gov under registration no. NCT04426383).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POSTOPERATIVE NEUROSURGICAL PATIENTS; PROTEIN-BINDING; PHARMACODYNAMIC PROPERTIES; MENINGITIS; INFECTIONS; DISEASE; vancomycin; population pharmacokinetics model; distal port; CSF protein; central nervous system infection; ventriculitis |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2024 10:04 |
| Last Modified: | 26 Mar 2024 10:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60572 |
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