Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis
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Vancomycin and meropenem are frequently used as empiric treatment for ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various factors with a high inter-individual variability. Because attaining and maintaining adequate concentrations of meropenem and vancomycin in the CSF is crucial for their bactericidal effect, we introduced a routine therapeutic drug monitoring (TDM) from CSF and serum for both antibiotics. We studied the antibiotic penetration into the CSF.
Patient data including serum and CSF concentrations for meropenem and vancomycin were collected in a retrospective fashion. Antibiotic CSF penetration ratio was calculated for each patient. Antibiotics were administered by continuous infusion aiming for serum target concentrations of 20–30 mg/L for vancomycin and 16–32 mg/L for meropenem.
Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs for vancomycin were studied. No patient suffered from renal or liver insufficiency. Mean vancomycin serum concentration was 22 ± 8 mg/L and the mean CSF concentration 4.5 ± 2.6 mg/L. CSF penetration was 20 ± 11% (coefficient of determination (R2) 0.02). For meropenem, the mean serum concentration was 30.7 ± 14.9 mg/L, mean CSF concentration 5.5 ± 5.2 mg/L, and a penetration of 18 ± 12%, R2 = 0.42.
Penetration of meropenem and vancomycin into the CSF is low while showing a high interindividual variability. Various patients in our study cohort were at risk for insufficient target attainment in CSF. Continuous administration of antibiotics under routine TDM appears to be a feasible and reasonable approach for optimization of intrathecal drug levels in patients suffering from ventriculitis. TDM might guide individual dosing adaptation and efforts to predict the CSF penetration of meropenem and vancomycin in cases of ventriculitis.
KeywordsCritical care Drug monitoring Pharmacokinetics Meropenem Vancomycin Cerebral ventriculitis
European Committee on Antimicrobial Susceptibility Testing
External ventricular drain
Gamma glutamyl transpeptidase
Glasgow Outcome Scale
High-performance liquid chromatography with ultra violet detection
Minimal inhibitory concentration
- SAPS II
Simplified Acute Physiology Score II
Therapeutic drug monitoring
MMM helped to design the study and to write the manuscript and acquired the data. PC helped to design the study and helped with the data acquisition. CK interpreted the data and helped to write the manuscript. VF helped to write the manuscript and to interpret the data. SK and MW helped with the interpretation and revised the manuscript. JG designed the study, wrote the manuscript, and helped to acquire the data. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
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