MOXIFLOXACIN IN THE THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS

The activity of moxifloxacin (BAY 12-8039) against a Streptococcus pne umoniae type 3 strain (MIC and minimum bactericidal concentration [MBC ] of moxifloxacin, 0.06 and 0.25 mu g/ml, respectively; MIC and MBC of ceftriaxone, 0.03 and 0.06 mu g/ml, respectively) was determined in v itro and in a rabbit model of meningitis. Despite comparable bacterici dal activity, 10 mu g of moxifloxacin per mi released lipoteichoic and teichoic acids less rapidly than 10 mu g of ceftriaxone per mi in vit ro. Against experimental meningitis, 10 mg of moxifloxacin per kg of b ody weight per mi reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone did (mean +/- standard deviatio n, -0.32 +/- 0.14 versus -0.39 +/- 0.11 Delta log CFU/ml/h), The activ ity of moxifloxacin could be described by a sigmoid dose-response curv e with a maximum effect of -0.33 Delta logCFU/ml/h and with a dosage o f 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 mu g /ml. Adjunctive treatment with dexamethasone at 1 mg/kg prior to the i nitiation of antibiotic treatment only marginally reduced the concentr ations of moxifloxacin in CSF (3.3 +/- 0.6 mu g/ml), In conclusion, mo xifloxacin may qualify for use in the treatment of S. pneumoniae menin gitis.