Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals.

Successful therapy of bacterial meningitis is dependent upon achieving adequate antibacterial activity in the CSF. The percent penetration (CSF concentration/serum concentration X 100) of various antimicrobial agents was determined in a rabbit model of bacterial meningitis. The percent penetration of the penicillin and cephalosporin derivatives was found to vary inversely with the protein binding of the respective drugs. Esterification of ampicillin increased its lipid solubility and likewise increased the penetration into the CSF. Probenecid competitively inhibits the active transport efflux of various organic acids from the CSF and increased the CSF concentrations of penicillin and cephalosporin derivatives. The percent penetration of all drugs was increased in the presence of the inflamed meninges.