THE PASSAGE OF CLOXACILLIN INTO CEREBROSPINAL-FLUID IN THE ABSENCE OFMENINGITIS

1 Eleven patients undergoing lumbar discectomy received cloxacillin by continuous i.v. infusion, starting before the operation. During the o peration several blood samples and one CSF sample were taken. 2 Mean r ate constants describing the passive transfer of drug from plasma to C SF (k(p)) and the largely active transfer in the opposite direction (k (CSF)) were estimated. 3 In some subjects the CSF albumin quotient, de fined as the ratio between the albumin concentration in CSF and in pla sma times 1000, was slightly elevated (up to 23) which caused a signif icant increase in the value of k(p). 4 The estimate of mean k(p) for h ealthy individuals was 0.065 h-1, which corresponds to a half-life of 10 h. The estimate of mean k(CSF) was 2.10 h-1. This predicts a steady -state CSF drug concentration which is 3% of the unbound plasma drug c oncentration. 5 There was a significant lag between the time courses o f plasma and CSF drug concentrations, presumably reflecting the time f or drug to move from the choroid plexus to the lumbar sampling site. 6 Four other patients received cloxacillin for prophylactic or therapeu tic reasons by continuous i.v. infusion. In three of those patients th e albumin quotient was normal or slightly elevated and the steady-stat e C(CSF)/Cu ratio was similar to the predicted normal value. 7 These f indings indicate that eradicating staphylococci from CSF in cases of m eningitis with a low degree of inflammation may be difficult.