Drug transfer into cerebrospinal fluid after simultaneous administration of ampicillin with ceftriaxone or ceftazidime in rabbits with Staphylococcus aureus meningitis.

Meningitis was induced in white rabbits with a non beta-lactamase producing strain of Staphylococcus aureus. There was no significant difference in the CSF level of ceftazidime after simultaneous administration of ceftazidime with ampicillin or after ceftazidime alone. In contrast the percentage CSF penetration of ampicillin decreased from 8.81% after administration of ampicillin alone to 2.77% after the simultaneous administration of ampicillin with ceftazidime. The ratio of AUC in CSF and serum was 19.4% after ampicillin alone and 7.71% after simultaneous administration with ceftazidime. When ceftriaxone was combined with ampicillin there was no effect on the CSF penetration of either drug. Cephalosporins have unpredictable effects on the CSF concentration of ampicillin, probably due to variable effects on the penetration of ampicillin from blood to CSF.