Concentrations of cefuzoname in cerebrospinal fluid (CSF) were determined in a total of 16 rabbits, 5 with healthy meninges, 5 with Staphylococcus aureus meningitis, and 6 with Escherichia coli meningitis. Mean percentages of the maximum concentration of the drug in CSF versus that in serum were 0.57, 3.37, and 4.40% for healthy rabbits, those with staphylococcal meningitis, and those with E. coli meningitis, respectively. The percentages of the area under the concentration-time curve of cefuzoname in CSF versus that in serum were, in the order of healthy group, staphylococcal meningitis group, and E. coli meningitis group, 0.61, 4.99, and 8.04% at 15 to 60 min, 1.44, 7.09, and 12.7% at 15 to 120 min, and 1.87, 8.07, and 15.8% at 15 to 180 min after administration, showing significant differences between the healthy and meningitis groups. All of the values in the E. coli meningitis group were greater than those of the staphylococcal meningitis group, but the differences were not significant. The ratios of the half-life of cefuzoname in CSF to that in serum were 2.10, 1.98, and 3.37 for the healthy, staphylococcal meningitis, and E. coli meningitis groups, respectively, with no significant difference between the three groups. Cefuzoname seems to be among the middle ranks of P-lactam agents as far as penetration rate is concerned; however, when its potent antibacterial activity and broad spectrum are taken into account, the concentrations in CSF in patients with meningitis seem worth examining.Cefuzoname (L-105) is a new, injectable cephalosporin developed by Lederle (Japan) Ltd. The compound has a wide antibacterial spectrum covering most aerobic and anaerobic gram-positive and gram-negative bacteria. The activity of cefuzoname is similar to that of cefazolin against staphylococci and to those of broad-spectrum cephems against gram-negative bacteria (M. Hikida, M. Inoue, and S. Mitsuhashi, Program Abstr. 24th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 733, 1984).In view of the antibacterial potency of cefuzoname, it was thought that the compound might be effective in the therapy of purulent meningitis if it showed good penetration into Staphylococcal meningitis was induced by a method reported previously (11). S. aureus FDA 209 P was cultured in brain heart infusion overnight, and a 5-ml portion of the culture was inoculated into 100 ml of brain heart infusion and then shake cultured for 3 h. The culture was centrifuged, and the resultant precipitates were washed three times by suspending them in physiological saline and centrifuging them. The final washed cells were resuspended in the physiological saline to an optical density of 0.7 at 550 nm. The viable cell count of this suspension was approximately 108/ml, and no decrease in the viable cell count was observed during a 3-month period while the suspension was stored at -20°C. A
