Morikawa Y, Haruta T, Fujiwara T, Kobayashi Y
Jpn J Antibiot. 1978 Jun;31(6):325-33.
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.
在兔金黄色葡萄球菌脑膜炎模型中评估了头孢菌素I、头孢噻吩和头孢唑林进入脑脊液(CSF)的情况,结果如下:1. 分别于单次静脉注射100mg/kg每种抗生素后1/2、1和2小时测定脑脊液中的浓度(微克/毫升)[脑脊液/血清比率(%)];头孢菌素I-7.5[8.9]、9.7[13.8]、9.1[22.6];头孢噻吩-0.42[3.6]、0.23[6.4]、未检测到[0];头孢唑林-7.5[11.8]、5.2[19.3]、2.0[17.5]。2. 比较静脉注射100mg/kg和200mg/kg头孢唑林后的结果,发现血药浓度有明确的剂量反应,但脑脊液浓度无此反应。3. 每种抗生素脑脊液浓度的标准误差大于青霉素,其进入脑脊液的“不可预测性”被认为是这三种药物进入脑脊液的共同特征之一。4. 低蛋白结合率的头孢菌素I和高蛋白结合率的头孢唑林进入脑脊液的情况无显著差异。结合率处于中间水平的头孢噻吩进入脑脊液的情况明显较低。这些结果表明,抗生素的蛋白结合率与其进入脑脊液的情况并不总是相关。5. 根据上述结果,对这三种抗生素在细菌性脑膜炎治疗中的临床适用性进行了文献综述。头孢噻吩进入脑脊液的转运率低以及头孢菌素I的肾毒性使其不适用于细菌性脑膜炎。头孢唑林被认为适用于治疗对氨苄西林耐药的大肠杆菌脑膜炎以及青霉素不适用的革兰氏阳性球菌脑膜炎。