Penicillin concentrations in cerebrospinal fluid and serum after intramuscular, intravenous, and oral administration to syphilitic patients.

Penicillin concentration in serum and cerebrospinal fluid (CSF) were estimated in 19 syphilitic patients given three different regimens: Penicillin G, 10 MIU i.v. three times a day (3 patients); procaine penicillin, 600 000 IU i.m. (11 patients); and penicillin V, 1.2 MIU by mouth four times a day (5 patients). Intravenous administration of penicillin G resulted in a penicillin concentration in CSF of 0.3-0.5 micrograms/ml; In contrast, procaine penicillin, i.m. and penicillin V by mouth did not result in any measurable CSF concentration, even in the presence of pleocytosis and/or barrier lesion. Penicillin V by mouth gave considerably higher serum concentrations than procaine penicillin intramuscular, however. In the light of these results, and reported treatment failures in neurosyphilis and demonstration of viable Treponema pallidum after treatment, we propose that neurosyphilis should be treated with high intravenous doses of penicillin to ensure treponemicidal concentrations in the central nervous system.