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JAC Advance Access published online on March 18, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn110
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect

Kyriaki Kanellakopoulou1,*, Alexandra Pagoulatou2, Konstantinos Stroumpoulis2, Marianthi Vafiadou2, Hariklia Kranidioti1, Helen Giamarellou1 and Evangelos J. Giamarellos-Bourboulis1

1 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece 2 Department of Anaesthesiology, Sismanoglion General Hospital, Athens, Greece

Received 22 September 2007; returned 20 January 2008; revised 3 February 2008; accepted 20 February 2008

* Corresponding author. Tel: +30-2105831665; Fax: +30-2105326446; E-mail: kyrkanel{at}yahoo.gr

Objectives: To evaluate the ability of moxifloxacin to penetrate healthy brain barriers.

Methods: Fifty patients received a single oral dose of 400 mg as an antimicrobial prophylaxis regimen for a short urological procedure under spinal anaesthesia. Serum and cerebrospinal fluid (CSF) were sampled at different time intervals post-drug intake and patients were divided into five groups, as follows: group I: 0.5–1 h; group II: 1–2 h; group III: 2–4 h; group IV: 4–6 h; and group V: 6–8 h. Concentrations of moxifloxacin were estimated after analysis by an HPLC system. Bactericidal activity of CSF samples of groups III and IV was assessed by a microdilution technique against two penicillin-resistant isolates of Streptococcus pneumoniae with MICs of moxifloxacin of 0.19 and 0.125 mg/L, respectively.

Results: Mean CSF concentrations of moxifloxacin of groups I, II, III, IV and V were 0.19, 0.87, 3.00, 4.07 and 1.82 mg/L, respectively. The mean bactericidal activity of CSF of group III was 8 and that of group IV was 4.

Conclusions: Single oral intake of 400 mg moxifloxacin is accompanied by good penetration through healthy meninges within 2–6 h post-dose and reached adequately high levels in human CSF exerting satisfactory bactericidal activity against penicillin-resistant S. pneumoniae. These results render novel perspectives for a role of moxifloxacin in CNS infections.

Key Words: penicillin resistance , brain barrier , Streptococcus pneumoniae


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