Nolan C M, Ulmer W C
J Infect Dis. 1980 Mar;141(3):326-30. doi: 10.1093/infdis/141.3.326.
One explanation for the failure of cephalothin to cure patients with bacterial meningitis is that desacetylcephalothin, as in vivo metabolite that has less antibacterial activity than the parent drug, penetrates more efficiently into cerebrospinal fluid (CSF); In experimental pneumococcal meningitis in rabbits, the peak levels of cephalothin and desacetylcephalothin in CSF after an intramuscular injection of 250 mg of cephalothin/kg were, respectively, 1.43 +/- 4.9 microgram/ml (2.8% of peak serum level) and 1.69 +/- 0.57 microgram/ml (2.2% of peak serum level). The observed half-life of desacetylcephalothin in CSF (3.32/hr) was longer (P less than 0.01) than that of cephalothin (0.72/hr). Choroid plexuses isolated from the lateral cerebral ventricles of rabbits with meningitis took up cephalothin in vitro more avidly than desacetylcephalothin (P less than 0.05), and metabolism of cephalothin to desacetylcephalothin by isolated choroid plexuses was demonstrated directly. Thus, intrathecal metabolism of cephalothin by the choroid plexus may contribute to the unsatisfactory performance of cephalothin in bacterial meningitis.
头孢噻吩治疗细菌性脑膜炎患者失败的一种解释是，去乙酰头孢噻吩作为一种体内代谢产物，其抗菌活性低于母体药物，但能更有效地穿透进入脑脊液（CSF）；在兔实验性肺炎球菌脑膜炎中，肌肉注射250mg头孢噻吩/kg后，脑脊液中头孢噻吩和去乙酰头孢噻吩的峰值水平分别为1.43±4.9微克/毫升（峰值血清水平的2.8%）和1.69±0.57微克/毫升（峰值血清水平的2.2%）。观察到去乙酰头孢噻吩在脑脊液中的半衰期（3.32/小时）比头孢噻吩的半衰期（0.72/小时）长（P<0.01）。从患有脑膜炎的兔大脑侧脑室分离出的脉络丛在体外摄取头孢噻吩比摄取去乙酰头孢噻吩更活跃（P<0.05），并且直接证明了分离出的脉络丛可将头孢噻吩代谢为去乙酰头孢噻吩。因此，脉络丛对头孢噻吩的鞘内代谢可能导致头孢噻吩在细菌性脑膜炎中的治疗效果不理想。
