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Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis
Abstract:
The concentrations of penicillin in the cerebrospinal fluid (CSF) were compared simultaneously with those in the serum in 17 patients with syphilis. The antibiotic concentrations were measured by the agar well diffusion method. There were no detectable concentrations of penicillin in the CSF after administration of benzathine penicillin 2.4 megaunits, benzathine penicillin 7.2 megaunits, procaine penicillin in aluminium monostearate (PAM) 12 megaunits, or aqueous procaine penicillin G 2.4 megaunits. Only after high doses of aqueous penicillin G 24 megaunits daily or aqueous penicillin G 2 megaunits daily together with oral probenecid 2 g daily was penicillin detectable in the CSF. The concentrations after the latter regimen were the highest and much higher than the minimum inhibitory concentration for Treponema pallidum.
Insights
Penicillin concentrations in cerebrospinal fluid (CSF) were undetectable with standard syphilis treatments. High-dose aqueous penicillin G, with or without probenecid, is required for detectable CSF penicillin levels.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Syphilis treatment relies on penicillin, but its penetration into the cerebrospinal fluid (CSF) is crucial for neurosyphilis.
- Understanding penicillin CSF concentrations is vital for optimizing treatment regimens.
Purpose of the Study:
- To compare penicillin concentrations in serum and CSF across various penicillin formulations and dosages in patients with syphilis.
- To determine the optimal penicillin regimens for achieving therapeutic CSF concentrations.
Main Methods:
- Simultaneous measurement of penicillin concentrations in serum and CSF of 17 syphilis patients.
- Utilized the agar well diffusion method for antibiotic concentration determination.
- Evaluated different penicillin formulations: benzathine penicillin, procaine penicillin in aluminium monostearate (PAM), and aqueous procaine penicillin G.
Main Results:
- No detectable penicillin CSF concentrations were observed with standard benzathine penicillin or lower-dose aqueous procaine penicillin G regimens.
- Penicillin was detectable in CSF only after high-dose aqueous penicillin G (24 megaunits/day) or combined with probenecid (2 megaunits/day + 2g probenecid/day).
- The highest and most effective CSF penicillin concentrations were achieved with the combination of high-dose aqueous penicillin G and probenecid, exceeding the minimum inhibitory concentration for Treponema pallidum.
Conclusions:
- Standard penicillin dosages and formulations are insufficient for achieving therapeutic CSF concentrations in syphilis patients.
- High-dose aqueous penicillin G, particularly when combined with probenecid, is necessary to ensure adequate penicillin penetration into the CSF for treating neurosyphilis.
- Further research into penicillin pharmacokinetics in the central nervous system is warranted.