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Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis

  • Original Article - Infection
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Abbreviations

ALAT:

Alanine aminotransferase

ASAT:

Aspartate aminotransferase

CRP:

C-reactive protein

CSF:

Cerebrospinal fluid

EUCAST:

European Committee on Antimicrobial Susceptibility Testing

EVD:

External ventricular drain

GGT:

Gamma glutamyl transpeptidase

GOS:

Glasgow Outcome Scale

HPLC-UV:

High-performance liquid chromatography with ultra violet detection

MIC:

Minimal inhibitory concentration

SAPS II:

Simplified Acute Physiology Score II

TDM:

Therapeutic drug monitoring

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Marius Marc-Daniel Mader, Patrick Czorlich & Manfred Westphal

  2. Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Christina König

  3. Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Christina König, Valentin Fuhrmann, Stefan Kluge & Jörn Grensemann

Authors
  1. Marius Marc-Daniel Mader
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  4. Valentin Fuhrmann
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  5. Stefan Kluge
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Contributions

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.

Corresponding author

Correspondence to Jörn Grensemann.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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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Comments

Mader and colleagues provide a study about interesting aspects of a common and difficult problem in neurointensive care: intrathecal penetration of meropenem and vancomycin in ventriculitis, in this study administered by continuous infusion and controlled by therapeutic drug monitoring of CSF and serum. The limitations of the study—in my opinion especially the retrospective design of the study and possible differences in extend and stage of the infections—have adequately been discussed by the authors. As well as the authors conclude, this reviewer recommends performing a prospective study with a larger number of patients about this important topic in the future.

Marcus Reinges

Bremen, Germany

This article is part of the Topical Collection on Infection

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Mader, M.MD., Czorlich, P., König, C. et al. Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis. Acta Neurochir 160, 2099–2105 (2018). https://doi.org/10.1007/s00701-018-3680-z

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