Effect of multidose therapy on cerebrospinal fluid penetration of cefazolin

The relationship between serum concentrations and cerebrospinal fluid (CSF) concentrations of cefazolin, and the association between these concentrations and neurotoxic reactions, were investigated. Samples of serum and spinal fluid were drawn simultaneously from six patients at the steady state on various dosages of cefazolin sodium for different conditions. The dose, dosing interval, number of doses, results of renal function tests, and signs of neurotoxicity, such as muscle twitches, confusion, and seizures, were recorded. The concentrations of cefazolin in the serum and CSF, total serum protein, and percent albumin were determined. Five of the six patients given multiple doses of cefazolin sodium had notable CSF accumulation of the drug (11.3 +/- 2.7% of the serum concentration). Three patients experienced generalized focal-motor seizures during their therapy. Neurotoxicity was found to be associated with renal dysfunction and multiple-dose therapy leading to serum concentrations greater than 360 micrograms/ml and CFS concentrations greater than 34 micrograms/ml. Cefazolin will penetrate into the CSF in patients receiving multiple-dose therapy of the drug. To avoid neurotoxicity, careful attention should be paid to the recommended dosage regimens, the impact of renal dysfunction on drug clearance should be recognized, and serum assays should be performed when necessary.