Pharmacodynamics and bactericidal activity of moxifloxacin in experimentalEscherichia coli meningitis

Moxifloxacin, an 8-methoxyquinolone with broad-spectrum activity in vitro, was studied in the rabbit model of Escherichia coli meningitis. The purpose s of this study were to evaluate the bactericidal effectiveness and the pha rmacodynamic profile of moxifloxacin in cerebrospinal fluid (CSF) and to co mpare the bactericidal activity with that of ceftriaxone and meropenem ther apy. After induction of meningitis, animals were given single doses of 10, 20, and 40 mg/kg or divided-dose regimens of 5, 10, and 20 mg/kg twice, sep arated by 6 h. After single doses, the penetration of moxifloxacin into pur ulent CSF, measured as percentage of the area under the concentration-time curve (AUC) in CSF relative to the AUC in plasma, was approximately 50%. Af ter single doses of 10, 20, and 40 mg/kg, the maximum CSF concentration (C- max) values were 1.8, 4.2, and 4.9 mug/ml, respectively; the AUC values (to tal drug) were 13.4, 25.4, and 27.1 mug/ml . h, respectively, and the half- life values (t1/2) were 6.7, 6.6, and 4.7 h, respectively. The bacterial ki lling in CSF for moxifloxacin, calculated as the Delta log(10) CFU per mill iliter per hour, at 3, 6, and 12 h after single doses of 10, 20, and 40 mg/ kg were -5.70, -6.62, and -7.02; -7.37, -7.37, and -6.87; and -6.62, -6.62, and -6.62, respectively, whereas those of ceftriaxone and meropenem were - 4.18, -5.24, and -4.43, and -3.64, -3.59, and -4.12, respectively. The CSF pharmacodynamic indices of AUC/MBC and C-max/MBC were interrelated (r = 0.8 1); there was less correlation with T > MBC (r = 0.74). In this model, ther apy with moxifloxacin appears to be at least as effective as ceftriaxone an d more effective than meropenem therapy in eradicating E. coli from CSF.