Cerebrospinal fluid penetration after combined administration of cefotaxime and ampicillin to rabbits with staphylococcal meningitis

Abstract

The pharmacokinetics of cefotaxime and ampicillin in the cerebrospinal fluid (CSF) were studied by a HPLC method after administering each of the antibiotics singly or as a mixture to rabbits with experimental meningitis caused by Staphylococcus aureus. The half-lives of cefotaxime and desacetyl-cefotaxime in the serum and of ampicillin in the CSF were found to be significantly shorter in the mixture group than in the respective single administration groups. No other statistically significant differences were observed between the mixture and single administration groups with respect to the maximum concentrations (Cmax) of the antibiotics in the serum and the CSF, to the relative percentage of the Cmax of each antibiotic in the CSF to the Cmax in the serum, and to the relative percentage of the AUC of each antibiotic in the CSF to that in the serum. These results differ from earlier findings that the concentration of ampicillin in the CSF of rabbits was significantly lower in animals concomitantly dosed with latamoxef (moxalactam) and ampicillin than in a group dosed only with ampicillin.

In vitro comparison of ampicillin-chloramphenicol and ampicillin-cefotaxime against 284 Haemophilus isolates

“…For example, Kobayashi et al (9) recently reported a beneficial pharmacokinetic interaction between ampicillin and cefotaxime, the former increasing the peak of the latter in cerebrospinal fluid and delaying the transformation to its less active metabolite. The initial management of bacterial meningitis with synergistic combinations rather than with antagonistic combinations or with one antibiotic alone appears to be a promising avenue toward improvement of the long-term prognosis of H. influenzae meningitis.…”

“…However, we encountered in our recent clinical trial (10) a Listeria meningitis; this microorganism is naturally resistant to cefotaxime. Kobayashi et al (9) initially treated a similar Listeria meningitis infection with cefotaxime alone; the patient died of the infection before appropriate therapy with ampicillin could be instituted.…”

Penetration of cefuzoname into the cerebrospinal fluid of rabbits

“…In view of the antibacterial potency of cefuzoname, it was thought that the compound might be effective in the therapy of purulent meningitis if it showed good penetration into Staphylococcal meningitis was induced by a method reported previously (11). S. aureus FDA 209 P was cultured in brain heart infusion overnight, and a 5-ml portion of the culture was inoculated into 100 ml of brain heart infusion and then shake cultured for 3 h. The culture was centrifuged, and the resultant precipitates were washed three times by suspending them in physiological saline and centrifuging them.…”