Treponemicidal levels of amoxicillin in cerebrospinal fluid after oral administration

Area of Science:

• Infectious Diseases
• Pharmacology
• Neurosyphilis Treatment

Background:

• Syphilis treatment traditionally relies on parenteral penicillin.
• Concerns exist regarding penicillin efficacy and patient compliance for neurosyphilis.
• Alternative oral regimens are needed to achieve adequate drug levels in the central nervous system.

Purpose of the Study:

• To evaluate the efficacy of oral amoxicillin combined with probenecid in achieving treponemicidal levels in serum and cerebrospinal fluid (CSF) of syphilis patients.
• To determine if this oral regimen can reach therapeutic concentrations in the CNS for treating neurosyphilis.

Main Methods:

• Seven patients with varying stages of syphilis received oral amoxicillin (6 g daily) and probenecid (2 g daily) for 15 days.
• Treponema pallidum immobilization assay was used to determine amoxicillin's treponemicidal level.
• Serum and CSF levels of amoxicillin were measured.

Main Results:

• The treponemicidal level of amoxicillin was determined to be 0.070 µg/ml, significantly higher than penicillin's 0.003 µg/ml.
• Considering the WHO-recommended penicillin level, the minimal effective amoxicillin level was estimated at 0.42 µg/ml.
• This estimated minimal level of amoxicillin was achieved in the serum and CSF of all treated patients.

Conclusions:

• Oral administration of amoxicillin and probenecid can achieve treponemicidal levels in the CSF.
• This regimen represents a potential alternative to parenteral penicillin for syphilis patients with suspected central nervous system involvement.
• Successful implementation requires ensuring reasonable patient compliance with the oral medication schedule.