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Antimicrobial Agents and Chemotherapy, July 1998, p. 1706-1712, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evaluation of Moxifloxacin, a New 8-Methoxyquinolone, for Treatment of Meningitis Caused by a PenicillinResistant Pneumococcus in Rabbits

Christian Østergaard,* Tina Klitmøller Sørensen, Jenny Dahl Knudsen, and Niels Frimodt-Møller

Division of Microbiology, Department of Clinical Microbiology, Statens Serum Institut, Copenhagen, Denmark

Received 20 August 1997/Returned for modification 21 February 1998/Accepted 25 April 1998

Moxifloxacin is a new 8-methoxyquinolone with high activity against gram-positive bacteria, including penicillin-resistant pneumococci. In an experimental meningitis model, we studied the pharmacokinetics of moxifloxacin in infected and uninfected rabbits and evaluated the antibiotic efficacies of moxifloxacin, ceftriaxone, and vancomycin against a penicillin-resistant Streptococcus pneumoniae strain (penicillin, ceftriaxone, vancomycin, and moxifloxacin MICs were 1, 0.5, 0.5, and 0.125 µg/ml, respectively). Moxifloxacin entered cerebrospinal fluid (CSF) readily, with peak values within 15 to 30 min after bolus intravenous infusion and with a mean percent penetration into normal and purulent CSF of approximately 50 and 80%, respectively. The bactericidal effect of moxifloxacin was concentration dependent, and regrowth was seen only when the concentration of moxifloxacin in CSF was below the minimal bactericidal concentration. All antibiotic-treated groups (moxifloxacin given in two doses of 40 mg/kg of body weight, moxifloxacin in two 20-mg/kg doses, ceftriaxone in one 125-mg/kg dose, and vancomycin in two 20-mg/kg doses) had significantly higher reductions in CSF bacterial concentration than the untreated group (P < 0.05). Moxifloxacin was as effective as vancomycin and ceftriaxone in reducing bacterial counts at all time points tested (3, 5, 10, and 24 h). Moreover, moxifloxacin given in two 40-mg/kg doses resulted in a significantly higher reduction in CSF bacterial concentration (in log10 CFU per milliliter) than vancomycin within 3 h after the start of antibiotic treatment (3.49 [2.94 to 4.78] versus 2.50 [0.30 to 3.05]; P < 0.05). These results indicate that moxifloxacin could be useful in the treatment of meningitis, including penicillin-resistant pneumococcal meningitis.

* Corresponding author. Mailing address: Division of Microbiology, Department of Clinical Microbiology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark. Phone: 45 32688208. Fax: 45 32683887. E-mail: coa{at}ssi.dk.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1706-1712, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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