A Pharmacologic Evaluation of Penicillin in Children with Purulent Meningitis

We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of 250,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 μg per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 μg per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P<0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high. (N Engl J Med 297:410–413, 1977) Penicillin G is the drug of choice for the treatment of meningococcal, gonococcal, pneumococcal and non-Group D streptococcal meningitis. Current reference sources present the pediatrician with a variety of dosage regimens ranging from 150,000 to 400,000 U per kilogram per day.^{1 2 3 4 5} A recent European textbook suggests intrathecal therapy in addition to the parenteral administration of penicillin.⁶ Logically, dosage should be based on known amounts needed to cause bactericidal concentrations of penicillin in cerebrospinal fluid; yet in a review of the medical literature we found only sporadic cerebrospinal-fluid penicillin concentrations reported.^{7 8 9 10 11 12 13 14 15 16 17} The absence of a controlled study of the pharmacokinetics of.