What is the treatment for syphilis?

Treatment of Syphilis

Parenteral penicillin G is the preferred drug for treatment of all stages of syphilis, with the specific preparation, dosage, and duration determined by the stage of infection. 1

Treatment Regimens by Stage

Primary and Secondary Syphilis

• Benzathine penicillin G, 2.4 million units IM in a single dose 2, 1
• Recent evidence confirms that a single dose is noninferior to three weekly doses for early syphilis, even in HIV-infected individuals 3

Early Latent Syphilis (infection within the past year)

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

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
• If a dose is missed in the weekly therapy course, clinical experience suggests that an interval of 10-14 days between doses might be acceptable before restarting the sequence of injections 4

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

Neurosyphilis

• Aqueous crystalline penicillin G is recommended for neurosyphilis treatment 2
• CSF examination is recommended for diagnosing neurosyphilis in patients with neurological signs/symptoms, tertiary syphilis, or those whose serological titers fail to decline appropriately 1

Alternative Treatments for Penicillin-Allergic Patients

Non-Pregnant Adults

• Primary and Secondary Syphilis: Doxycycline 100 mg orally twice daily for 14 days 1, 5
• Late Latent Syphilis: Doxycycline 100 mg orally twice daily for 28 days 1
• Doxycycline has been shown to be effective for early syphilis with no treatment failures in comparative studies 6

Pregnant Women and Neurosyphilis Patients

• Penicillin remains the only proven effective therapy; patients should undergo desensitization if they report penicillin allergy 2, 1
• Skin testing for penicillin allergy may be useful before desensitization 2

Special Populations

HIV-Infected Patients

• Treatment regimens are the same as for non-HIV-infected patients 1
• No added benefit has been demonstrated with enhanced antimicrobial therapy for HIV-infected persons with syphilis 4
• HIV-infected patients may have atypical serologic responses but generally respond well to standard treatment 2

Pregnant Women

• Parenteral penicillin G is the only therapy with documented efficacy for preventing maternal transmission 2, 1
• The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress but should not prevent or delay therapy 2

Follow-Up and Monitoring

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

Management of Sex Partners

• Persons exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 2
• Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 2
• Sexual transmission of T. pallidum occurs only when mucocutaneous syphilitic lesions are present, which are uncommon after the first year of infection 2

Important Clinical Considerations

• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after any syphilis therapy, especially in early syphilis 2
• Patients should be informed about this possible adverse reaction, which may include headache, myalgia, and other symptoms 2
• Neither combinations of benzathine penicillin and procaine penicillin nor oral penicillin preparations are appropriate for syphilis treatment 2
• Azithromycin resistance in T. pallidum has emerged, limiting its use as an alternative treatment 7

Pitfalls to Avoid

• Do not use oral penicillin preparations for syphilis treatment as they are ineffective 2
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 2
• Do not confuse the "serofast state" (persistent low-level positive nontreponemal tests despite adequate treatment) with treatment failure 8
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 2