A REVIEW OF THERAPEUTIC MONITORING OF CHLORAMPHENICOL IN PATIENTS WITH HAEMOPHILUS-INFLUENZAE MENINGITIS

Two hundred and seventy-seven serum chloramphenicol concentrations in 90 patients with Haemophilus influenzae type b meningitis were analysed retrospectively- Most patients were given chloramphenicol 25 mg/kg 6 hourly initially. Chloramphenicol concentrations were categorized as pre-dose ('trough') or post-dose ('peak'). Twenty-six per cent of the results were in the potentially toxic range (above 30 mg/L), and 18% were below 10 mg/L. Analysis of 46 pre- and post-dose measurements showed that for the intravenous (i.v.) route of administration, 23% of the pre-dose concentrations were higher than the corresponding post-dose levels and, for the oral route, 42% of the pre-dose levels were higher. Multivariate analysis of covariance demonstrated that chloramphenicol concentrations decreased significantly with increasing number of days of treatment and that the decline was steeper with i.v. administration. The results of this study emphasize the need for therapeutic monitoring of chloramphenicol concentrations, and suggest that chloramphenicol should be given as a loading dose of 40 mg/kg, followed by 25 mg/kg per dose 8 hourly for 3-4 days and then 6 hourly.