Cefoperazone pharmacokinetics in acute childhood meningitis

We studied the serum pharmacokinetics and cerebrospinal fluid concentrations of cefoperazone in 15 children with acute meningitis. Mean cefoperazone concentrations of 117 micrograms/ml in the serum and 3.8 micrograms/ml in the cerebrospinal fluid were noted 2 hours after a single 100 mg/kg dose. Following multiple 50 or 100 mg/kg doses, the mean peak serum cefoperazone concentrations were 232 and 498 micrograms/ml, respectively, with an overall mean elimination phase half-life of 2.12 hours. The data best fit a linear, two-compartment model. Cerebrospinal fluid concentrations 1.5 to 2.5 hours after the end of cefoperazone infusions ranged from 1.4 to 19.2 micrograms/ml for all doses and states of illness. This represented 1.2% to 6.4% of simultaneous serum values. The cerebrospinal fluid inhibitory titer was greater than or equal to 1:16 in 17 of 18 specimens tested against a strain of Haemophilus influenzae type b resistant to both chloramphenicol and ampicillin. In the doses given, cefoperazone produces adequate cerebrospinal fluid concentrations and bioactivity to treat the common bacterial forms of acute meningitis in infants and children.