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Updated: Oct 12, 2025
Intraventricular Drug Delivery and Sampling for Pharmacokinetics and Pharmacodynamics Study
Published on: March 31, 2022
Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided
Christoph Tiede1, Ute Chiriac2, Daniel Dubinski3
1Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe University, 60590 Frankfurt am Main, Germany.
Abstract:
Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20-30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.
Insights
Optimizing antibiotic therapy for cerebral infections like ventriculitis requires addressing low cerebrospinal fluid (CSF) penetration. Continuous infusion and therapeutic drug monitoring (TDM) of meropenem and vancomycin can achieve effective CSF concentrations.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Antibiotic penetration into cerebrospinal fluid (CSF) is often limited, complicating treatment of cerebral infections like meningitis and ventriculitis.
- Continuous infusion and therapeutic drug monitoring (TDM) are strategies to optimize antimicrobial exposure.
Purpose of the Study:
- To evaluate an individualized dosing strategy using continuous infusion and TDM for meropenem and vancomycin in ventriculitis patients.
- To determine serum and CSF concentrations and CSF penetration rates of these antibiotics.
Main Methods:
- Retrospective analysis of meropenem and vancomycin serum and CSF concentrations in nine ventriculitis patients.
- Continuous infusion dosing guided by TDM, aiming for target CSF concentrations.
- Calculation of CSF penetration percentages.
Main Results:
- Initial median dosing: meropenem 8.8 g/24h, vancomycin 4.25 g/24h.
- Median serum concentrations: meropenem 21.3 mg/L, vancomycin 24.5 mg/L.
- Median CSF concentrations: meropenem 3.4 mg/L, vancomycin 1.7 mg/L; median CSF penetration: meropenem 15%, vancomycin 7%.
Conclusions:
- Continuous infusion and TDM-guided dosing are effective for achieving therapeutic CSF concentrations of meropenem and vancomycin in ventriculitis.
- Dose optimization within 48 hours ensured sufficient CSF levels in all patients.
- This approach is reasonable for overcoming limited antibiotic penetration in cerebral infections.
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