Penetration of cefotaxime and moxalactam into cerebrospinal fluid of rabbits with experimentally induced Escherichia coli meningitis

Abstract

Penetration of the new beta-lactam antibiotics cefotaxime and moxalactam into cerebrospinal fluid (CSF) was studied in rabbits with experimentally produced Escherichia coli meningitis. Cefotaxime reached peak concentrations (mean +/- SEM) of 31.9 +/- 5.4 micrograms/ml in serum and 2.8 +/- 0.3 micrograms/ml in CSF after an infusion of 50 mg/kg per hr for 8 hr. Moxalactam, after an infusion of 12.5 mg/kg per hr iv, produced peaks of 31.0 +/- 13.1 micrograms/ml in serum and 9.7 +/- 1.2 micrograms/ml in CSF. Both drugs reduced the initial concentration of E. coli in the CSF by greater than 1,000-fold. An infusion of 100 mg/kg per hr of cephalothin produced a peak concentration of 76.5 +/- 15.2 micrograms/ml in serum but resulted in a concentration of only 0.17 +/- 0.05 micrograms/ml in CSF and had no bactericidal activity in CSF. Paper chromatography of CSF from cefotaxime-treated rabbits showed that 85.3% (+/- 3.1%) of the antibiotic activity was ascribed to desacetylcefotaxime, a metabolite that is less potent than the parent drug. Neither cefotaxime nor moxalactam was taken up in vitro by rabbit choroid plexus tissue, but cephalothin was taken up at a rate of 9.6 +/- 1.1 microgram/g per hr. Perhaps cefotaxime and moxalactam reached higher concentrations in CSF than did cephalothin because they are not removed from the CSF by the exit pump of the choroid plexus. The fact that levels of cefotaxime in CSF are lower than those of moxalactam could be attributed to the presence of desacetylcefotaxime, a metabolite that is less active than cefotaxime.