[Experimental studies on the passage of antibiotics into cerebrospinal fluid in staphylococcal meningitis in rabbits. II. Cephaloridine, cephalothin and cefazolin (author's transl)]

Abstract

Passage of cephaloridine, cephalothin and cefazolin into cerebrospinal fluid (CSF) was evaluated in Staphylococcus aureus meningitis in rabbits and the following results were obtained. 1. Concentration in CSF (microgram/ml) [CSF/serum ratio (%)] was determined 1/2, 1 and 2 hours after a single intravenous injection of 100 mg/kg of each antibiotic, respectively; cephaloridine-7.5 [8.9], 9.7 [13.8], 9.1 [22.6]; cephalothin-0.42 [3.6], 0.23 [6.4], not detectable [0]; cefazolin-7.5 [11.8], 5.2 [19.3], 2.0 [17.5]. 2. When results with cefazolin after an intravenous injection 100 mg/kg and 200 mg/kg were compared, a definite dose response was noted in blood concentration but not in CSF concentration. 3. A standard error of CSF concentrations of each antibiotic was larger than that of penicillins, and "Unpredictability" of their passage into CSF was considered to be one of the characteristics common to these three drugs in respect of their passage into CSF. 4. There was no significant difference noted in antibiotic passage into CSF between cephaloridine of low protein binding rate and cefazolin of very high binding rate. Cephalothin, of which binding rate was intermediate, showed a remarkably lower passage into CSF. These results indicate that a correlation does not always exist between protein binding rate of the antibiotics and their passage into CSF. 5. Based on the above results, a review of the literature was made on clinical applicability of these three antibiotics in the treatment of bacterial meningitis. Low transport rate of cephalothin into CSF and nephrotoxicity of cephaloridine make them to be unsuitable for bacterial meningitis. Cefazolin is considered to be suitable in the treatment of ampicillin-resistant Escherichia coli meningitis and Gram-positive coccal meningitis in which penicillins are not applicable.