What is the recommended treatment for possible syphilis exposure?

Treatment for Possible Syphilis Exposure

Persons exposed within 90 days of a partner's diagnosis of primary, secondary, or early latent syphilis should receive presumptive treatment with benzathine penicillin G 2.4 million units IM as a single dose, even if their serologic tests are negative. 1, 2

Exposure Timeline and Treatment Algorithm

Recent Exposure (≤90 days)

• Treat presumptively regardless of serologic status because exposed individuals may be infected even if seronegative 1, 2
• Administer benzathine penicillin G 2.4 million units IM as a single dose 1, 2, 3
• This approach prevents progression to symptomatic disease and interrupts transmission chains 1

Exposure >90 Days Ago

• Treat presumptively if serologic results are not immediately available AND follow-up is uncertain 1, 2
• If serologic testing is readily available and follow-up is assured, base treatment on test results and clinical evaluation 1
• For partners of patients with high nontreponemal titers (≥1:32) and unknown duration, assume early syphilis and treat presumptively 1, 2

Specific Treatment Regimens

Standard Treatment (Non-Allergic Patients)

• Benzathine penicillin G 2.4 million units IM in a single dose 1, 2, 3
• This is the only therapy with documented efficacy backed by over 50 years of clinical experience 1
• Parenteral penicillin G remains the gold standard for all stages of syphilis 2, 3

Penicillin-Allergic Patients

• Doxycycline 100 mg orally twice daily for 14 days 2, 3, 4
• This is the recommended alternative for non-pregnant adults with penicillin allergy 2, 4
• The FDA-approved dosing is 100 mg every 12 hours for 2 weeks for early syphilis 4

Pregnant Women

• Penicillin desensitization is mandatory - pregnant women with syphilis exposure who report penicillin allergy must undergo desensitization and receive penicillin 1, 2
• Parenteral penicillin G is the only therapy with documented efficacy for preventing maternal transmission 2, 3
• No alternative antibiotics are acceptable in pregnancy 1, 2

Critical Clinical Considerations

Jarisch-Herxheimer Reaction

• Warn patients about this acute febrile reaction that occurs within 24 hours of treatment 1, 2, 3
• Symptoms include fever, headache, and myalgia, occurring most commonly in early syphilis 1, 2
• Antipyretics may be used but do not prevent the reaction 1
• In pregnant women, this reaction may induce early labor or fetal distress, but this concern should not delay treatment 1, 2

HIV-Infected Individuals

• Use the same treatment regimens as non-HIV-infected patients for exposure prophylaxis 2, 3
• HIV-infected patients may have atypical serologic responses but generally respond well to standard treatment 2, 3
• All patients treated for syphilis exposure should be tested for HIV 3

Common Pitfalls to Avoid

• Do not use oral penicillin preparations - they are ineffective for syphilis treatment 1
• Do not delay treatment waiting for serologic results in recent exposures (≤90 days) or when follow-up is uncertain 1, 2
• Do not use combinations of benzathine and procaine penicillin - these are not appropriate for syphilis treatment 1
• Do not substitute other antibiotics in pregnancy - only penicillin after desensitization is acceptable 1, 2

Follow-Up Recommendations

• Exposed individuals should undergo serologic testing at baseline and repeat testing at 3,6, and 12 months 2
• A fourfold decline in nontreponemal test titers is expected within 6 months for those who develop early syphilis 2, 3
• Use the same serologic test method (VDRL or RPR) consistently for monitoring, as results cannot be directly compared between methods 2