JAC Advance Access published online on March 31, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh158
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Neurology,
University Hospital, Innsbruck;
* Corresponding author. E-mail: christian.joukhadar{at}univie.ac.at.
Received 1 December 2003
; revised 26 January 2004
; accepted 2 February 2004
Objective: The present study was performed
to test the ability of fosfomycin to penetrate into the CSF of neurointensive
care patients with ventriculostomy-associated ventriculitis. Patients and methods: Six patients requiring
neurointensive care monitoring, including extraventricular drainage
due to secondary obstructive hydrocephalus, were enrolled into the
study. All patients received 8 g of fosfomycin intravenously three
times a day over a period of at least 5 days. Concentrations of
fosfomycin in the CSF and plasma were measured after single-dose
administration and at steady state. Results: Mean values of the fosfomycin area
under the time-concentration curves for the dosing interval
of 8 h (AUC8) were 929 ± 280
and 225 ± 131 mg·h/L for plasma
and CSF after single-dose administration, respectively (P < 0.03).
The ratios of the AUC8 for CSF to the AUC8 for
plasma were 0.23 ± 0.07 after a single
dose and 0.27 ± 0.08 following multiple
doses (P > 0.05, not significant). Additional in vitro experiments have shown that fosfomycin
exerts non-concentration-dependent microbial growth inhibition.
At steady state, the time above MIC (t > MIC)
values were 98%, 92% and 61% for pathogens
with MIC values of 8, 16 and 32 mg/L, respectively. Conclusion: The present pharmacokinetic study
indicates that 8 g of fosfomycin three times per day should provide
sufficient antimicrobial concentrations in the CSF for the overall
treatment period. Thus, the co-administration
of fosfomycin could be useful for the treatment of ventriculitis
caused by susceptible pathogens.
Keywords: CSF, intensive care, pharmacokinetics, humans
Concentrations of fosfomycin in the cerebrospinal
fluid of neurointensive care patients with ventriculostomy-associated ventriculitis
2 Department
of Pharmacology and Toxicology,
Karl-Franzens-University, Graz;
3 Department
of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University
of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel
18-20, A-1090 Vienna;
4 Department
of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University
of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel
18-20, A-1090 Vienna; Institute
of Pharmacology, University of Vienna, Vienna, Austria
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