Concentrations of cefoperazone in cerebrospinal fluid during bacterial meningitis

Cefoperazone was administered to 15 patients with bacterial meningitis before lumbar punctures were performed. Patients received one of the following three dosage regimens before collection of cerebrospinal fluid (CSF): one dose of 50 mg/kg (maximum, 2 g; group I), one dose of 100 mg/kg (maximum, 4 g; group II), three doses of 100 mg/kg each every 8 h (maximum, 4 g each dose; group III). Of 44 CSF samples, 26 had detectable cefoperazone levels (59%); drug concentrations in CSF ranged from less than 0.8 to 11.5 micrograms/ml (median, 1.97 micrograms/ml). Although the percentage of patients with detectable cefoperazone levels in CSF was higher in group III (69%) than in group II (64%) or group I (50%), the differences were not statistically significant; however, the mean drug concentration in CSF in group I (1.53 micrograms/ml) was significantly lower than that in group III (3.1 micrograms/ml). A high protein concentration in CSF (as an indicator of meningeal inflammation) correlated best with high cefoperazone concentrations in CSF. These findings differ from previous investigations of cefoperazone penetration into CSF; however, cefoperazone may not penetrate reliably into CSF and therefore may not be an optimal candidate drug for the treatment of bacterial meningitis.