What is the recommended treatment for chancre (primary stage of syphilis)?

Treatment of Chancre (Primary Syphilis)

Benzathine penicillin G 2.4 million units administered as a single intramuscular injection is the definitive treatment for chancre (primary syphilis). 1, 2

First-Line Treatment

• Benzathine penicillin G 2.4 million units IM as a single dose is the only recommended first-line therapy for primary syphilis, supported by over 40 years of clinical experience. 3, 1, 2
• This regimen is effective regardless of HIV status—HIV-infected patients receive the same single-dose treatment as HIV-negative patients. 1, 2
• Penicillin remains the treatment of choice for all stages of syphilis because it is the only therapy with proven efficacy across all patient populations. 3, 1

Alternative Regimens for Penicillin-Allergic Patients

For non-pregnant patients with documented penicillin allergy:

• Doxycycline 100 mg orally twice daily for 14 days is the preferred alternative. 1, 4
• Tetracycline 500 mg orally four times daily for 14 days is another option, though compliance is typically better with doxycycline due to less frequent dosing. 1, 2
• Ceftriaxone 1 g daily (IM or IV) for 8-10 days may be considered, though optimal dosing is not definitively established. 1

Critical caveat: Azithromycin should NOT be used in the United States due to widespread macrolide resistance in T. pallidum and documented treatment failures, despite some older studies suggesting efficacy. 1, 5

Special Population Considerations

Pregnant Patients

• Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment—no alternatives are acceptable. 1, 2
• Penicillin is the only therapy proven to prevent congenital syphilis, and substituting with inadequate alternatives risks fetal complications. 2
• All pregnant women should be screened for syphilis at the first prenatal visit, during the third trimester, and at delivery. 2

HIV Co-infection

• HIV-infected patients receive the same single-dose benzathine penicillin G regimen as HIV-negative patients. 1, 2
• However, closer follow-up is required (every 3 months rather than every 6 months) due to increased risk of neurologic complications and treatment failure. 1
• All patients with syphilis should be tested for HIV infection. 2, 6

Follow-Up Protocol

• Clinical and serologic evaluation using quantitative nontreponemal tests (RPR or VDRL) should be performed at 6 and 12 months after treatment. 1, 2
• A fourfold decline in nontreponemal test titers is expected within 6 months for primary syphilis. 2, 7
• HIV-infected patients require more frequent monitoring at 3-month intervals. 1

Treatment failure is defined as:

• Persistent or recurring signs/symptoms 1
• Sustained fourfold increase in nontreponemal test titers 1
• Failure of initially high titers to decline at least fourfold within 6-12 months 2

Management of Sexual Partners

• Sex partners exposed within 90 days preceding the diagnosis should be treated presumptively, even if seronegative. 2
• For primary syphilis specifically, partners exposed within 3 months plus the duration of symptoms are at risk and require treatment. 2
• Partners exposed more than 90 days before diagnosis should be treated presumptively if serologic results are not immediately available and follow-up is uncertain. 2

Important Clinical Considerations

Jarisch-Herxheimer Reaction

• An acute febrile reaction (fever, headache, myalgia) may occur within 24 hours after treatment, especially in early syphilis. 1, 2
• Patients should be counseled about this expected reaction before treatment. 2
• In pregnant women during the second half of pregnancy, this reaction may precipitate premature labor or fetal distress, and women should seek immediate medical attention if they notice changes in fetal movements or contractions. 2

Common Pitfalls to Avoid

• Never use oral penicillin preparations—they are ineffective for syphilis treatment. 2
• Do not switch between different nontreponemal test methods (RPR vs. VDRL) when monitoring serologic response, as results cannot be directly compared. 2
• Do not rely on treponemal test antibody titers (FTA-ABS, TP-PA) to assess treatment response—these remain positive for life and correlate poorly with disease activity. 2
• Ensure patients with compliance concerns or uncertain follow-up undergo desensitization and receive penicillin rather than alternative regimens. 1