What is the recommended treatment for a patient with a positive syphilis test?

Treatment for Positive Treponemal Antibody Test (51.80)

For a patient with positive treponemal antibodies, you must first obtain a quantitative nontreponemal test (RPR or VDRL) to determine disease activity and guide treatment, as using only one type of test is insufficient for accurate diagnosis. 1

Immediate Diagnostic Steps

• Obtain quantitative nontreponemal testing (RPR or VDRL) on serum to complete the diagnostic algorithm, as both treponemal and nontreponemal tests are required for accurate syphilis diagnosis 1
• Review any prior syphilis testing results and documented treatment history to determine if this represents new infection, inadequately treated infection, or successfully treated past infection 1
• Perform a thorough physical examination looking specifically for: primary chancre, secondary syphilis rash, lymphadenopathy, neurologic signs, or cardiovascular manifestations 2

Treatment Algorithm Based on Serologic Pattern

If RPR/VDRL is Reactive (Positive)

Stage the infection based on clinical findings and history:

• Primary or Secondary Syphilis (chancre present, rash, symptoms within past year): Benzathine penicillin G 2.4 million units IM as a single dose 3
• Early Latent Syphilis (acquired within preceding year based on documented seroconversion, fourfold titer increase, or partner with early syphilis): Benzathine penicillin G 2.4 million units IM as a single dose 3
• Late Latent or Unknown Duration: Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 3

If RPR/VDRL is Non-Reactive (Negative)

This serologic pattern (treponemal positive/nontreponemal negative) most commonly represents late latent syphilis with waning nontreponemal antibodies or successfully treated past infection. 1

• Without documented adequate prior treatment: Treat as late latent syphilis with benzathine penicillin G 2.4 million units IM weekly for 3 weeks 1
• With documented adequate prior treatment and appropriate serologic decline: No treatment needed, but clinical follow-up recommended 1

Penicillin Allergy Management

Non-Pregnant Patients

• Primary/Secondary or Early Latent Syphilis: Doxycycline 100 mg orally twice daily for 14 days 3, 4
• Late Latent Syphilis: Doxycycline 100 mg orally twice daily for 28 days 3, 4
• Alternative option: Ceftriaxone 1 gram IV/IM daily for 10 days (based on randomized trial data showing comparable efficacy) 3

Pregnant Patients

Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment—there are no acceptable alternatives. 3

• Penicillin is the only therapy proven to prevent congenital syphilis and treat fetal infection 2
• Erythromycin and azithromycin cannot be relied upon to cure an infected fetus 2
• Tetracyclines and doxycycline are contraindicated in pregnancy 2

Special Populations

HIV-Infected Patients

• Use the same treatment regimens as HIV-negative patients 3
• Standard serologic tests remain accurate for most HIV-infected patients, though atypical responses can occur 2
• Require closer follow-up with serologic testing at 3,6,9,12, and 24 months to detect potential treatment failure 2, 3
• Some experts recommend CSF examination before treatment for early syphilis in HIV-infected patients 2

Neurosyphilis Considerations

• Perform CSF examination if: neurological signs/symptoms present, tertiary syphilis, treatment failure (serologic titers fail to decline fourfold within 6 months for early syphilis), or HIV infection with neurologic symptoms 3
• CSF leukocyte count >5 WBCs/mm³ is a sensitive indicator for neurosyphilis 1
• Treatment requires aqueous crystalline penicillin G (not benzathine penicillin) 3

Critical Follow-Up Requirements

Serologic Monitoring

• Use the same nontreponemal test method (RPR or VDRL) from the same laboratory for all follow-up testing, as results cannot be compared between different test types 1, 3
• Expected response for early syphilis: Fourfold decline in nontreponemal titer within 6 months 3, 5
• Expected response for late latent syphilis: Slower decline over 12-24 months, and serologic response may be minimal 1, 5
• Treatment failure definition: Failure of nontreponemal titers to decline fourfold within 6 months for primary/secondary syphilis 3

Follow-Up Schedule

• Early syphilis: Clinical and serologic evaluation at 3,6,12, and 24 months 3
• Late latent syphilis: Clinical follow-up recommended, though serologic changes may be minimal 1

Essential Additional Testing

• Test for HIV infection in all patients with syphilis 2
• Test for other sexually transmitted infections including gonorrhea and chlamydia 6
• Pregnancy test for all women of childbearing age before treatment 2

Partner Management

• Persons exposed within 90 days of diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 3
• Persons exposed >90 days before diagnosis should be treated presumptively if serologic results are not immediately available and follow-up is uncertain 3

Important Clinical Pitfalls to Avoid

• Never rely on treponemal test results alone to make treatment decisions—nontreponemal testing is essential 1
• Never use oral penicillin preparations for syphilis treatment as they are ineffective 3
• Never substitute azithromycin due to widespread macrolide resistance and documented treatment failures in the United States 3
• Warn patients about Jarisch-Herxheimer reaction: acute febrile reaction with headache and myalgia that may occur within 24 hours after treatment, especially in early syphilis 3
• In pregnant women treated during second half of pregnancy: Jarisch-Herxheimer reaction may precipitate premature labor or fetal distress; advise immediate medical attention for changes in fetal movements or contractions 3