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Antimicrobial Agents and Chemotherapy, October 2003, p. 3104-3108, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3104-3108.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

Federico Pea,1* Federica Pavan,1 Ennio Nascimben,2 Claudio Benetton,2 Pier Giorgio Scotton,3 Alberto Vaglia,3 and Mario Furlanut1

Institute of Clinical Pharmacology & Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine,1 Department of Anaesthesia and ICU,2 Department of Infectious Diseases, Regional Hospital Ca' Foncello, Treviso, Italy3

Received 13 January 2003/ Returned for modification 15 May 2003/ Accepted 23 June 2003

In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (Cmax ss)was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the Cmax ss in CSF to the Cmax ss in plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC0-{tau}s) were 47.69 mg · h/liter for plasma and 33.42 mg · h/liter for CSF, with the ratio of the AUC0-{tau} for CSF to the AUC0-{tau} for plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ± 1.57 and 5.51 ± 1.36 h, respectively; P = 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.

* Corresponding author. Mailing address: Institute of Clinical Pharmacology & Toxicology, DPMSC, University of Udine, P. le S. Maria della Misericordia 3, 33100 Udine, Italy. Phone and fax: 39 0432 559833. E-mail: federico.pea{at}med.uniud.it.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3104-3108, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3104-3108.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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  • Pfausler, B., Spiss, H., Dittrich, P., Zeitlinger, M., Schmutzhard, E., Joukhadar, C. (2004). Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis. J Antimicrob Chemother 53: 848-852 [Abstract] [Full Text]  


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