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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.

Penicillin is undoubtedly the antibiotic most effective on Treponema pallidum, but is it possible to prescribe it according to a standard regimen? Experimentation proves that such a uniform therapeutic plan cannot be determined for the following reasons: 1) Treponema pallidum may divide every 30 to 33 hours, but this concept is only established during the period of exponential growth in the initial lesion. Moreover, if Treponema pallidum are very quickly disseminated throughout the organism, then they do not divide at the same rate. In addition, we take into account a whole series of factors which can interfere with their rate of multiplication. 2) A penicillinemia of 0.03 U/ml may kill all the Treponema pallidum when they divide, but Dr. Eagle's data, although this would be a fairly active serum level, showed that the effective maximal serum concentration should be far higher, about 0.820 U/ml. The experimental data prove it is not possible to point out an accurate correlation between blood and tissue levels; thus, the penicillin levels in the cerebrospinal fluid are about 1/100 lower than those obtained in the serum. Among other factors it is necessary to take into account not only the age of the patient but also the penicillin complex chosen. Although the total of injected penicillin can be the same, the kinetics of serum levels are essentially variable, both regarding the increase of levels and duration according to the drug used. 3) As noted it follows that penicillinotherapy prescribed early with high and prolonged doses may allow a bacteriologic sterilization of primary syphilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Can penicillin be considered as an infallible treatment for syphilis? Some practitioners have hoped and even believed that this antibiotic would be able to eradicate this infection. To support their thesis, they have put forward an uniform standard therapeutic plan capable of being applied to any stage of the disease and which is based upon the following syllogism: a) all T.p. would divide every 30-33 hours. b) a level of penicillinemia of 0.03 IU/ml would destroy all Treponema when they divide. c) thus, a penicillin therapy administered 3 times giving such levels in serum during a period of 33 hours would produce a bacteriological sterilization of the infected organism. But statistics have shown that these conceptions were wrong. As a matter of fact: 1) every biological research has clearly proved that it is wrong to assert such a rhythm of division for all T.p. Since this multiplication is submitted to a succession of factors that we know more or less well, thus, during the latency phase, T.p. vegetate inside the tissues without apparently multiplying so quickly. 2) For lack of being able to cultivate T.p., it is not possible to state which is the activity level of penicillin on this germ. 3) Finally, the kinetic elimination of penicillin varies extremely, particularly depending on the drug which is used with patients, and on the localization of these germs. All experimental and clinical studies agree and insist on the fact that penicillin therapy must be given early in the infection, at a prolonged and high dose; results having to be estimated on the serological answers, especially with repeated TPI and FTA tests. As far as the late phases of the disease are concerned, for lack of being able to cultivate T. pallidum and because we do not have any absolute criterion of any bacteriological sterilization, the serological answers being often positive, circumspection has always to be a rule: it is better to admit what we do not know rather than to assert without any proof.

Paired specimens of cerebrospinal fluid and serum were taken from 21 patients to estimate penicillin concentrations two to three hours after the last dose of a course of 14-21 daily intramuscular injections of procaine penicillin 0.6 MU. Of 10 patients treated with procaine penicillin alone, eight had no detectable penicillin and two had sub-treponemicidal concentrations (less than 0.018 mg/l) in the cerebrospinal fluid. Of 11 patients treated with procaine penicillin as above and probenecid 2 g a day by mouth, three had no detectable penicillin, two had sub-treponemicidal concentrations, and six had treponemicidal concentrations of penicillin in the cerebrospinal fluid. All 21 patients had treponemicidal concentrations of penicillin in the serum. This dose of procaine penicillin alone or with probenecid is therefore not recommended for treating neurosyphilis.

Treponemicidal levels of penicillin in the CSF were not obtained following intramuscular (IM) injections of 600,000 IU of penicillin G procaine along with 2% aluminum monostearate (PAM). Treponemicidal levels of penicillin in the CSF were achieved in 31 patients by probenecid, 500 mg/6 hr by mouth, with penicillin G, 500,000 IU by IM injection, and by probenecid every six hours by mouth and IM injections of penicillin G procaine once a day in two of three patients following injections of 600,000 IU, in four of five following 1.2 million IU, and in three (now all nine) following 2.4 million IU.