Concentrations of cefoperazone in cerebrospinal fluid during bacterial meningitis

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Abstract
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.