Moxifloxacin in the Therapy of Experimental Pneumococcal Meningitis

Abstract

ABSTRACT The activity of moxifloxacin (BAY 12-8039) against a Streptococcus pneumoniae type 3 strain (MIC and minimum bactericidal concentration [MBC] of moxifloxacin, 0.06 and 0.25 μg/ml, respectively; MIC and MBC of ceftriaxone, 0.03 and 0.06 μg/ml, respectively) was determined in vitro and in a rabbit model of meningitis. Despite comparable bactericidal activity, 10 μg of moxifloxacin per ml released lipoteichoic and teichoic acids less rapidly than 10 μg of ceftriaxone per ml in vitro. Against experimental meningitis, 10 mg of moxifloxacin per kg of body weight per ml reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone did (mean ± standard deviation, −0.32 ± 0.14 versus −0.39 ± 0.11 Δlog CFU/ml/h). The activity of moxifloxacin could be described by a sigmoid dose-response curve with a maximum effect of −0.33 ΔlogCFU/ml/h and with a dosage of 1.4 mg/kg/h producing a half-maximal effect. Maximum tumor necrosis factor activity in CSF was observed later with moxifloxacin than with ceftriaxone (5 versus 2 h after the initiation of treatment). At 10 mg/kg/h, the concentrations of moxifloxacin in CSF were 3.8 ± 1.2 μg/ml. Adjunctive treatment with dexamethasone at 1 mg/kg prior to the initiation of antibiotic treatment only marginally reduced the concentrations of moxifloxacin in CSF (3.3 ± 0.6 μg/ml). In conclusion, moxifloxacin may qualify for use in the treatment of S. pneumoniae meningitis.