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.