A Study of Cephalothin and Desacetylcephalothin in Cerebrospinal Fluid in Therapy for Experimental Pneumococcal Meningitis

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Abstract
One explanation for the failure of cephalothin to cure patients with bacterial meningitis is that desacetylcephalothin, an in vivo metabolite that has less antibacterial activity than the parent drug, penetrates more efficiently into cerebrospinal fluid (CSF). In experiinental 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 μg/ml (2.8070 of peak serum level) and 1.69 ± 0.57 μg/ml (2.2070 of peak serum level). The observed half-life of desacetylcephalothin in CSF (3.32/hr) was longer (P < 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 < 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.

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