We evaluated the diffusion of pefloxacin into the cerebrospinal fluid (CSF) in 15 patients with bacterial meningitis or ventriculitis, 14 of whom were treated with other antibiotics. Three doses of pefloxacin were administered at 12-h intervals to 11 patients intravenously and to 4 patients orally. Individual doses were 7.5 mg/kg in seven patients and 15 mg/kg in eight patients. Plasma and CSF levels were determined by a highperformance liquid chromatographic assay. The concentrations of pefloxacin in CSF were measured 2 h after the third intravenous dose and 4 h after the third oral dose. In patients receiving 7.5 mg/kg, peak levels in plasma ranged from 6.8 to 16 ,ug/ml, and trough levels were from 2 to 7.5 ,ug/ml. Concentrations in CSF ranged from 2.4 to 9 ,ug/ml. In patients receiving 15 mg/kg, peak levels in plasma ranged from 14 to 18.6 tig/ml, and trough levels were from 4 to 13.2 ,ug/ml. Concentrations in CSF ranged from 6.5 to 13 ,ug/ml. These preliminary data indicate that pefloxacin diffuses well into the CSF of patients with inflamed meninges.Pefloxacin is a new methyl-4-piperazinyl quinolone with high activity against both gram-negative and gram-positive organisms

The serum protein binding, extravascular diffusion and urinary excretion of pefloxacin were studied in rabbits. The effect of furosemide on the urinary excretion of pefloxacin was investigated. In an experimental model of Escherichia coli endocarditis, diffusion into heart valves and infected vegetations and bactericidal effect of pefloxacin were also studied. We observed a serum protein binding of 25%. Extravascular concentrations found were within the range of the minimal inhibitory concentrations for most susceptible strains. Pefloxacin appeared to be reabsorbed by renal tubules (fractional excretion: 61 +/- 21%). Furosemide significantly increased the renal excretion of pefloxacin through a tubular process. We observed a good penetration of pefloxacin into normal heart valves and infected vegetations. Pefloxacin reduced the colony counts in infected vegetations after seven im injections of the drug (given as 15 mg/kg/12 h).