From the Guidelines
A single dose of benzathine penicillin G (Bicillin) is recommended for routine treatment of acute syphilis in its early stages (primary, secondary, and early latent syphilis of less than one year's duration). The standard regimen is a single intramuscular injection of 2.4 million units of benzathine penicillin G. For patients with late latent syphilis (infection of more than one year's duration) or syphilis of unknown duration, a three-dose regimen is recommended, consisting of 2.4 million units of benzathine penicillin G administered intramuscularly once weekly for three consecutive weeks (total 7.2 million units) 1. This difference in treatment duration is based on the understanding that longer-standing infections require more prolonged therapy to effectively eliminate the spirochete Treponema pallidum, which can establish persistent infection in tissues.
Some key points to consider:
- Penicillin remains the treatment of choice for syphilis because T. pallidum is highly sensitive to penicillin, and no resistance has been documented despite decades of use 1.
- For patients with penicillin allergy, doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) may be used as an alternative, though desensitization to penicillin is preferred for pregnant women with penicillin allergy 1.
- Data on 1 versus 3 doses of intramuscular benzathine penicillin G (BPG) for treatment of early syphilis in human immunodeficiency virus (HIV)–infected patients remain limited, though most studies suggest no difference in serologic outcomes between 1 and >1 dose of BPG 1.
Overall, the most recent and highest quality study 1 supports the use of a single dose of benzathine penicillin G for early syphilis, with a three-dose regimen recommended for late latent syphilis or syphilis of unknown duration.
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 regimen for routine treatment of acute syphilis is a single dose of 2,400,000 units of benzathine penicillin G (Bicillin) for primary, secondary, and latent syphilis 2. However, for late (tertiary and neurosyphilis) syphilis, a 3-dose regimen is recommended, with 2,400,000 units administered at 7-day intervals 2.
From the Research
Treatment Regimens for Acute Syphilis
- A single dose of benzathine penicillin G (Bicillin) is recommended for the routine treatment of acute syphilis, as supported by studies 3, 4, 5, 6.
- The use of a single dose of 2.4 million units of benzathine penicillin G has been shown to be effective in treating early syphilis, with treatment success rates of 90% to 100% 5.
- Multiple-dose treatment of early syphilis is not necessarily more effective, especially in HIV-infected individuals, as evidenced by studies 3, 6.
- The Centers for Disease Control and Prevention recommend a single dose of benzathine penicillin G for the treatment of early syphilis, including in HIV-infected patients 3, 4.
Comparison of Single-Dose and 3-Dose Regimens
- A randomized clinical trial found that a 3-dose regimen of benzathine penicillin G did not improve syphilis serological outcomes compared to a single dose 3.
- Another study found that treatment response was the same among those receiving 1 or >1 dose of benzathine penicillin G, with a treatment response rate of 92% 6.
- The use of a single dose of benzathine penicillin G is supported by the majority of the evidence, with no significant benefit shown for multiple-dose regimens 3, 4, 5, 6.