What is the recommended dose of Penicillin G (Benzylpenicillin) for the treatment of syphilis?

From the Guidelines

The recommended treatment for syphilis is benzathine penicillin G, with the specific dose and duration depending on the stage and clinical manifestations of the disease. For primary, secondary, or early latent syphilis (less than one year duration), a single dose of benzathine penicillin G 2.4 million units administered intramuscularly is recommended 1. For late latent syphilis (more than one year duration) or syphilis of unknown duration, the recommended regimen is benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks (total 7.2 million units). Some key points to consider when treating syphilis include:

• Penicillin remains the treatment of choice for syphilis because Treponema pallidum, the causative organism, is highly sensitive to penicillin, and the drug can cross the blood-brain barrier to treat neurosyphilis 1.
• Patients with penicillin allergy should undergo desensitization if possible, as alternative antibiotics are less effective.
• Following treatment, clinical and serological follow-up is essential to ensure cure, typically at 3,6, and 12 months after treatment.
• For neurosyphilis or ocular syphilis, aqueous crystalline penicillin G 3-4 million units intravenously every 4 hours or as a continuous infusion for 10-14 days is recommended. It's worth noting that while alternative treatments such as doxycycline, azithromycin, and ceftriaxone may be considered in certain cases, penicillin remains the preferred treatment due to its high efficacy and ability to cross the blood-brain barrier 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... 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 recommended dose of penicillin G for syphilis is:

• Primary, secondary, and latent: 2,400,000 units (1 dose) 2
• Late (tertiary and neurosyphilis): 2,400,000 units at 7-day intervals for three doses 2

From the Research

Penicillin G Dose for Syphilis

• The recommended dose of penicillin G for the treatment of syphilis is a single intramuscular injection of 2.4 million units of benzathine penicillin G 3, 4.
• This dose is effective for the treatment of early syphilis, with studies reporting 90% to 100% treatment success rates 4.
• The use of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals 4.
• Penicillin G is the drug of choice for the treatment of syphilis, and doxycycline is an acceptable alternate option if penicillin cannot be used 5.
• The Centers for Disease Control and Prevention continues to recommend the use of penicillin G as the first-line therapy for the treatment of syphilis 5, 6.

Special Considerations

• In HIV-infected persons, there is no added benefit to enhanced antimicrobial therapy when treating syphilis 3, 5.
• Pregnant women should be treated with penicillin G, and missed doses are not acceptable 5.
• A cerebrospinal fluid examination to diagnose neurosyphilis is recommended in certain cases, such as persons diagnosed with tertiary syphilis or those with neurological signs or symptoms consistent with neurosyphilis 3, 5.