JAC Advance Access originally published online on March 31, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 848-852
© 2004 The British Society for Antimicrobial Chemotherapy
Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis
1 Department of Neurology, University Hospital, Innsbruck; 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 Institute of Pharmacology, University of Vienna, Vienna, Austria
Received 1 December 2003, returned 23 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
* Corresponding author. Tel: +43-1-40400-2981; Fax: +43-1-40400-2998; E-mail: christian.joukhadar{at}univie.ac.at
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