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

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.

[Penetration of cephaloridine and cephalothin into the cerebrospinal fluid-clinical study (author's transl)].

There were 35 cases, treated with Cephaloridine or Cephalothin after neurosurgical operation. Neurological surgeon always troubled with passage of blood-brain barrier when drug was given. Antibiotics was not exceptionally, therefore we, neurological surgeon, must select the effective drug to bacterium, that which penetrated enough to the intracranial organ through the blood-brain barrier. In this paper, we measured the concentration of Cephaloridine and Cephalothin into cerebrospinal fluid in the cases with non inflammatory meninges. We collected the cerebrospinal fluid from continued ventricle tap and serum, then measured the concentration of the drug with bioassay. Cephaloridie treated cases. 22 cases. 1) 1 g intramuscular injection. 4 cases. Serum level got to highest value, 64 mug/ml (mean value) 1 hour after injection. CSF level got to maximum concentration 46.8 mug/ml. (mean value) serum mean level 21.5 mug/ml. CSF mean level 0.73 mug/ml. 2) 1 g 3 minutes-intravenous injection 5 cases. Serum level got to highest value 67.5 mug/ml. CSF maximum level was 5.25 mug/ml. Serum mean level 19.74 mug/ml. CSF mean level 0.61 mug/ml. 3) 1 g 1 hour-intravenous drip. 9 cases. Serum maximum level 121.0 mug/ml. CSF maximum level 2.30 mug/ml. Serum mean level 20.08 mug/ml. CSF mean level 0.67 mug/ml. 4) 1 g 8 hours-intravenous drip. 3 cases. Serum maximum level 61.0 mug/ml. CSF maximum level 1.36 mug/ml. Serum mean level 14.78 mug/ml. CSF mean level 0.47 mug/ml. Cephalothin treated cases, 12 cases. 1) 1 g 8 hours-intravenous drip, 4 cases. In fact we could detect the drug only in one case, in CSF, and we could not in other three cases. In KF - 4 case, serum maximum concentration was 26.0 mug/ml, CSF maximum concentration was 0.07 mug/ml. Serum mean level 16.97 mug/ml. CSF mean level 0.01 mug/ml 2) 2 g 1 hour-intravenous drip, 9 cases. Serum maximum level 690.0 mug/ml. CSF maximum level 2.03 mug/ml. Serum mean level 29.59 mug/ml. CSF mean level 0.06 mug/ml. In cephaloridine cases, the tendency was observed, that which, as concentration of the drug in CSF increased, cell count and protein decreased, and, as concentration of the drug decreased, cell count and protein increased. CSF/serum concentration ratio of Cephaloridine increased, when time passed, in intramuscular, 3 minutes intravenous, and 1 hour-intravenous drip group. Then only in 8-hours-intravenous prip group. Then only in 8-hours-intravenous drip group, concentration ratio decreased. In Cephaloridine group, mean value of CSF/serum ratio showed. 1 g i.m. 0.084 1 g 3 minutes-i.v. 0.098 1 g 1 hour-i.v. 0.194 1 g 8 hours-i.v. 0.044.