What is the recommended dosage for treating syphilis?

Syphilis Treatment Dosage Guidelines

The recommended dosage for treating syphilis is benzathine penicillin G 2.4 million units IM in a single dose for primary, secondary, and early latent syphilis, and 7.2 million units total (administered as three doses of 2.4 million units IM each at 1-week intervals) for late latent syphilis or syphilis of unknown duration. 1, 2

Treatment by Stage of Infection

Primary and Secondary Syphilis

• Benzathine penicillin G 2.4 million units IM in a single dose 1, 3
• For children: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 2, 4

Early Latent Syphilis (acquired within the preceding year)

• Benzathine penicillin G 2.4 million units IM in a single dose 1, 2
• Early latent syphilis is defined based on documented seroconversion, fourfold increase in titer, history of symptoms, or having a sex partner with documented early syphilis 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1, 2
• If a dose is missed during weekly therapy, an interval of 10-14 days between doses might be acceptable before restarting the sequence 5

Tertiary Syphilis

• Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1, 2

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours for 10-14 days 1, 3

Alternative Treatments for Penicillin-Allergic Patients

Non-Pregnant Adults

• Primary and Secondary Syphilis: Doxycycline 100 mg orally twice daily for 14 days 1, 3, 6
• Late Latent Syphilis: Doxycycline 100 mg orally twice daily for 28 days 1, 2, 6

Special Populations

• Pregnant women: Only penicillin G is proven effective for preventing maternal transmission; penicillin-allergic pregnant women should undergo desensitization 1, 2
• HIV-infected patients: Same treatment regimens as non-HIV-infected patients, but closer follow-up is recommended (every 3 months rather than every 6 months) 1, 3

Administration Considerations

• Benzathine penicillin G should be administered by DEEP INTRAMUSCULAR INJECTION in the upper, outer quadrant of the buttock (dorsogluteal) or the ventrogluteal site 4
• In neonates, infants, and small children, the midlateral aspect of the thigh may be preferable 4
• The anterolateral thigh is not recommended due to potential adverse effects 4
• When doses are repeated, vary the injection site 4
• Both single-dose (2.4 million units) and divided doses (1.2 million units in each buttock) are equally well tolerated for administration 7

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests should be repeated at regular intervals (3,6,12, and 24 months) 1, 2
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1, 2
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 2

Important Clinical Considerations

• Recent research has shown that for HIV-infected patients with early syphilis, single-dose benzathine penicillin G plus doxycycline achieved higher serologic responses than benzathine penicillin G alone during a 12-month follow-up period 8
• However, a randomized clinical trial comparing single-dose versus 3-dose regimens of benzathine penicillin G for early syphilis in HIV-infected individuals found no significant difference in treatment success rates 9
• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after treatment, especially in early syphilis 1, 3

Common Pitfalls to Avoid

• Do not use oral penicillin preparations for syphilis treatment as they are ineffective 1
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 1
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 1
• Macrolide resistance in T. pallidum is widespread in the United States, making azithromycin an unsuitable alternative despite some evidence of efficacy 3, 10