What is the recommended course of action for syphilis treatment if the interval between the first and second dose of benzathine penicillin G (BPG) is less than 7 days?

From the Guidelines

If the interval between the first and second dose of benzathine penicillin G (BPG) for syphilis treatment is less than 7 days, the recommended course of action is to restart the entire treatment regimen. The second dose should be administered 7 days after the first dose, and if this interval is shorter, the first dose should be considered invalid and the treatment schedule should begin again. For primary, secondary, or early latent syphilis, the complete regimen consists of a single dose of 2.4 million units of BPG intramuscularly. For late latent syphilis or syphilis of unknown duration, the regimen requires three doses of 2.4 million units of BPG intramuscularly at one-week intervals (days 1,8, and 15) 1. This recommendation ensures adequate treponemicidal levels of penicillin in the blood and tissues for the time required to treat the infection effectively. Penicillin has a relatively short half-life, and the benzathine formulation provides slow release over time, which is why proper spacing between doses is crucial for maintaining therapeutic levels throughout the treatment period. Some specialists recommend additional therapy in some patients, but evidence is insufficient to recommend specific regimens for these situations 1. Key considerations in the management of syphilis include:

• Ensuring adequate treatment duration to prevent treatment failure and reduce the risk of complications
• Proper spacing of doses to maintain therapeutic levels of penicillin
• Consideration of additional therapy in certain situations, such as pregnancy or congenital syphilis
• Monitoring for treatment response and potential complications, such as neurosyphilis or otologic syphilis 1. Overall, the goal of syphilis treatment is to effectively eradicate the infection, prevent complications, and reduce the risk of transmission to others 1.

From the FDA Drug Label

Syphilis Primary, secondary, and latent—2,400,000 units (1 dose). Late (tertiary and neurosyphilis)—2,400,000 units at 7-day intervals for three doses. The FDA drug label does not answer the question.

From the Research

Syphilis Treatment Interval

• The recommended course of action for syphilis treatment if the interval between the first and second dose of benzathine penicillin G (BPG) is less than 7 days is not explicitly stated in the provided studies.
• However, a study 2 suggests that if a patient misses a dose of penicillin in a course of weekly therapy for late syphilis, an interval of 10-14 days between doses might be acceptable before restarting the sequence of injections.
• The same study 2 also mentions that pharmacologic considerations suggest that an interval of 7-9 days between doses, if feasible, may be more optimal.
• It is essential to note that missed doses are not acceptable for pregnant women, as stated in the study 2.
• There is no direct evidence in the provided studies to support a specific course of action for an interval of less than 7 days between the first and second dose of BPG.

Alternative Treatments

• Doxycycline is considered a second-line treatment for syphilis, and studies 3, 4 have compared its effectiveness with benzathine penicillin G.
• The study 4 found that doxycycline is still an effective agent for the treatment of early syphilis, with no statistically significant differences in serological responses at 6 and 12 months after treatment compared to benzathine penicillin G.
• Another study 3 found that doxycycline had a slightly lower success rate when compared with penicillin in treating primary syphilis, but appeared to have a reduced success rate in attaining resolution in late and undetermined syphilis infection.

Considerations

• The management of syphilis requires careful consideration of various factors, including the stage of the disease, patient demographics, and potential comorbidities, as discussed in the study 2.
• Frequent serological screening of high-risk populations, such as men who have sex with men, is recommended to prevent reinfection and transmission, as stated in the study 2.