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Neurocritical Care
Published in: Neurocritical Care 1/2019

01-08-2019 | Pharmacokinetics | Original Article

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis

Authors: S. Piva, Antonello Di Paolo, Laura Galeotti, Francesco Ceccherini, Francesco Cordoni, Liana Signorini, Tommaso Togni, Amedeo De Nicolò, Frank A. Rasulo, Nazzareno Fagoni, N. Latronico, Antonio D’Avolio

Published in: Neurocritical Care | Issue 1/2019

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Abstract

Background

There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg.

Results

In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7–1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17–6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04–9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%.

Conclusions

Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.
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Metadata
Title
Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis
Authors
S. Piva
Antonello Di Paolo
Laura Galeotti
Francesco Ceccherini
Francesco Cordoni
Liana Signorini
Tommaso Togni
Amedeo De Nicolò
Frank A. Rasulo
Nazzareno Fagoni
N. Latronico
Antonio D’Avolio
Publication date
01-08-2019
Publisher
Springer US
Published in
Neurocritical Care / Issue 1/2019
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-018-0657-y

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