What is the recommended dosage regimen of penicillin (Penicillin) for syphilis treatment?

From the Guidelines

The most effective treatment for syphilis involves administering penicillin, with the number of doses depending on the stage of infection, and for early-stage syphilis, a single intramuscular injection of 2.4 million units of benzathine penicillin G is recommended 1.

Key Considerations for Syphilis Treatment

• The stage of syphilis infection is crucial in determining the treatment regimen.
• For primary, secondary, or early latent syphilis, a single dose of benzathine penicillin G is typically sufficient.
• For late latent syphilis or syphilis of unknown duration, three doses of benzathine penicillin G administered at one-week intervals are recommended.
• Neurosyphilis, ocular syphilis, or tertiary syphilis require more intensive treatment with aqueous crystalline penicillin G.

Treatment Regimens

• For early-stage syphilis, a single intramuscular injection of 2.4 million units of benzathine penicillin G is the recommended treatment 1.
• For late latent syphilis or syphilis of unknown duration, three doses of benzathine penicillin G 2.4 million units administered intramuscularly at one-week intervals are recommended.
• Alternative regimens, such as procaine penicillin plus probenecid, may be considered in certain cases, but their effectiveness is not as well established 1.

Special Considerations

• Patients allergic to penicillin should undergo desensitization if possible, as alternative antibiotics are less effective.
• Follow-up serologic testing is essential to confirm treatment success.
• Pregnant women should be treated according to the stage of their infection using the same regimens.

Evidence-Based Recommendations

• The Centers for Disease Control and Prevention (CDC) recommend penicillin as the treatment of choice for syphilis, regardless of HIV status 1.
• The most recent guidelines emphasize the importance of proper treatment and follow-up to prevent complications and ensure effective treatment outcomes.

From the FDA Drug Label

Syphilis (neurosyphilis) 12 to 24 million units/day, as 2 to 4 MU every 4 hours for 10 to 14 days; many experts recommend additional therapy with Benzathine PCN G 2. 4 MU IM weekly for 3 doses after completion of IV therapy Syphilis (congenital and neurosyphilis) after the newborn period 200,000 to 300,000 units/kg/day (administered as 50,000 units/kg every 4 to 6 hours) for 10 to 14 days

The decision on the number of penicillin doses to give in syphilis treatment is based on the severity of the infection and the patient's weight.

• For adult patients with neurosyphilis, the recommended dose is 12 to 24 million units/day, administered as 2 to 4 million units (MU) every 4 hours for 10 to 14 days.
• For pediatric patients with congenital or neurosyphilis, the recommended dose is 200,000 to 300,000 units/kg/day, administered as 50,000 units/kg every 4 to 6 hours for 10 to 14 days. It is also recommended that many experts suggest additional therapy with Benzathine PCN G 2.4 MU IM weekly for 3 doses after completion of IV therapy 2.

From the Research

Deciding on Penicillin Doses for Syphilis Treatment

To determine the appropriate number of penicillin doses for syphilis treatment, several factors should be considered, including the stage of syphilis, HIV status, and treatment response.

• The current recommendation for early syphilis treatment is a single dose of 2.4 million units of benzathine penicillin G, as supported by studies 3, 4, 5, 6, 7.
• For HIV-infected patients with early syphilis, a single dose of benzathine penicillin G is as effective as multiple doses, with studies showing no significant difference in treatment response 3, 6, 7.
• The treatment response is generally assessed by monitoring the decline in rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) titers, with a ≥4-fold decline indicating a good response 3, 5, 6.
• Factors such as CD4 cell count and pretreatment titers may affect treatment response, but the number of penicillin doses does not appear to impact treatment outcome in HIV-infected patients with early syphilis 6, 7.

Considerations for Specific Patient Populations

• For patients with late or late latent syphilis, the evidence for treatment is limited, and the optimal treatment regimen is unclear 4, 5.
• Pregnant women with syphilis should be treated with penicillin, but the optimal dose and duration of treatment are not well established 5.
• Patients with neurosyphilis require more intensive treatment, typically with intravenous penicillin G, but the optimal treatment regimen is not well defined 4, 5.