Human cerebrospinal fluid pharmacokinetics and treatment of bacterial meningitis with ceftizoxime

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Abstract
Single doses of ceftizoxime (30 mg/kg; 12-min influsion) were administered to 12 patients with bacterial meningitis prior to routinely scheduled lumbar punctures. Cerebrospinal fluid (CSF) ceftizoxime concentrations were determined by microbiological assay in samples collected at 2 h following administration. CSF concentrations ( n = 41) ranged from nondetectable to 17.0 mg/l (mean, 4.9 mg/l), and CSF/serum ratios ranged from 0–107.6% (mean, 22.5%. Higher CSF concentrations were observed in CSF with high protein concentration or leukocyte counts during earlier days of therapy and in samples obtained at greater than 120 min following drug administration. Five patients (9 months-65 years) with pneumococcal (3), meningococcal (1) and haemophilus (1) meningitis were treated with ceftizoxime (200 mg/kg/day, intravenously). All treated patients had sterile CSF at 24–36 h after initiation of therapy. CSF concentrations ( n = 12) of ceftizoxime ranged from < 0.5–29 mg/l (mean, 12.8 mg/l). Clinical outcome was comparable with conventional antibiotic therapy, and no patient relapsed.

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