What are the guidelines for treating a patient exposed to syphilis, including testing and treatment options for non-pregnant and pregnant individuals, and those with penicillin allergies?

Syphilis Exposure Guidelines

Immediate Management of Exposed Individuals

Persons exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis in a sexual partner should be treated presumptively with benzathine penicillin G 2.4 million units IM as a single dose, even if their serologic tests are negative. 1

Risk-Based Exposure Windows

The time periods for identifying at-risk sexual partners vary by stage of the index case's infection:

• Primary syphilis: 3 months plus duration of symptoms 1
• Secondary syphilis: 6 months plus duration of symptoms 1
• Early latent syphilis: 1 year 1

Management Algorithm for Exposures >90 Days

For persons exposed more than 90 days before the diagnosis:

• If serologic results are immediately available and negative: Clinical and serologic follow-up is appropriate 1
• If serologic results are not immediately available AND follow-up is uncertain: Treat presumptively 1
• If follow-up can be ensured: Obtain serologic testing and treat based on results 1

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Treatment Regimens by Population

Non-Pregnant Adults Without Penicillin Allergy

First-line treatment: Benzathine penicillin G 2.4 million units IM as a single dose for presumptive treatment of early syphilis exposure 1, 2

This regimen is appropriate for:

• Confirmed exposure to primary syphilis 1
• Confirmed exposure to secondary syphilis 1
• Confirmed exposure to early latent syphilis 1

Non-Pregnant Adults With Penicillin Allergy

Recommended alternative: Doxycycline 100 mg orally twice daily for 14 days 3, 1, 4

Second alternative: Tetracycline 500 mg orally four times daily for 14 days 3

Important caveats:

• Close follow-up is essential for penicillin-allergic patients 3
• Doxycycline has better compliance than tetracycline due to less frequent dosing 3
• Ceftriaxone 1 gram IM/IV daily for 10-14 days may be considered, but data are limited and clinical experience is insufficient to identify late failures 3, 1
• Do not use azithromycin in the United States due to widespread macrolide resistance and documented treatment failures 1
• Erythromycin 500 mg orally four times daily for 14 days is less effective than other regimens and should only be used when compliance can be ensured 3

Pregnant Women

All pregnant women exposed to syphilis must be treated with penicillin, regardless of allergy status. 3, 1

Critical management steps:

1. If penicillin-allergic: Desensitization is mandatory, followed by benzathine penicillin G 2.4 million units IM 3, 1
2. No alternatives are acceptable: Penicillin is the only therapy with documented efficacy for preventing maternal transmission to the fetus and treating fetal infection 1
3. Tetracycline, doxycycline, erythromycin, azithromycin, and ceftriaxone are inadequate because erythromycin does not reliably cure fetal infection 1

Special monitoring considerations:

• Women treated during the second half of pregnancy are at risk for premature labor and/or fetal distress from Jarisch-Herxheimer reaction 1
• Pregnant women beyond 20 weeks gestation with early syphilis require fetal and contraction monitoring for 24 hours after initiating treatment 5
• Women should seek immediate obstetric attention if they experience contractions or decreased fetal movement during the first 24 hours post-treatment 1, 5

Screening requirements for pregnant women:

• Screen at first prenatal visit 1
• Screen during third trimester 1
• Screen at delivery 1

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Testing Strategy for Exposed Individuals

Initial Evaluation

All exposed individuals should undergo serologic testing using the two-step approach:

1. Screening: Nontreponemal test (RPR or VDRL) 2, 6
2. Confirmation: Treponemal test (FTA-ABS or MHA-TP) if nontreponemal test is positive 2, 6

Follow-Up Testing Schedule

For individuals treated presumptively who were initially seronegative:

• Repeat serologic testing at 6 weeks, 3 months, and 6 months to detect seroconversion 1
• If seroconversion occurs, evaluate for treatment failure and consider re-treatment 3

For individuals with positive serology at baseline who receive treatment:

• Quantitative nontreponemal tests at 6 and 12 months 1, 2
• Expect a fourfold decline in titer within 6 months for early syphilis 1, 2

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Special Populations and Considerations

HIV-Infected Individuals

Treatment regimens are the same as for non-HIV-infected patients, but management differs:

• Use the same penicillin regimens for all stages 1
• More frequent follow-up is required: Evaluate at 3-month intervals instead of 6-month intervals 3
• If penicillin-allergic, undergo skin testing and desensitization, then treat with penicillin 1
• HIV-infected patients with late latent syphilis or syphilis of unknown duration should have CSF examination 3

Pediatric Patients

For children with acquired syphilis exposure:

Early latent syphilis: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 3, 1

Late latent syphilis or unknown duration: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units, administered as three doses at 1-week intervals (total 150,000 units/kg up to adult total dose of 7.2 million units) 3, 1

Important: Children require CSF examination to exclude neurosyphilis before treatment 1

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Treatment Failure and Re-Treatment

Defining Treatment Failure

Treatment failure should be suspected if:

• Persistent or recurring signs or symptoms develop 3
• Sustained fourfold increase in nontreponemal test titer compared to baseline or subsequent result 3
• Failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 3, 1

Management of Treatment Failure

1. Re-evaluate for HIV infection 3
2. Unless reinfection is certain, perform lumbar puncture to evaluate for neurosyphilis 3
3. Re-treatment regimen: Three weekly injections of benzathine penicillin G 2.4 million units IM, unless CSF examination indicates neurosyphilis 3

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Jarisch-Herxheimer Reaction Management

Understanding the Reaction

The Jarisch-Herxheimer reaction is an acute febrile reaction that occurs within the first 24 hours after antibiotic therapy, particularly common in patients with early syphilis 5

Common symptoms include:

• Fever 5
• Headache 5
• Myalgia 5
• Chills 5

Management Approach

1. Continue penicillin therapy: JHR is self-limiting and does not indicate treatment failure or allergy 5
2. Provide supportive care: Antipyretics (acetaminophen or NSAIDs) for symptom relief 5
3. Patient counseling before treatment is essential: Warn all patients about the possibility of JHR to prevent confusion with drug allergy and unnecessary treatment discontinuation 5

Special Pregnancy Considerations

• JHR may induce premature labor or fetal distress, but this risk should never prevent or delay appropriate penicillin therapy 1, 5
• Pregnant women beyond 20 weeks gestation require intensive monitoring for 24 hours after treatment initiation 5
• Counsel patients to seek immediate obstetric attention if contractions or decreased fetal movement occur 5

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Critical Pitfalls to Avoid

Treatment Errors

• Never use oral penicillin preparations for syphilis treatment—they are ineffective 1
• Never substitute inadequate alternatives in pregnancy: Only penicillin prevents congenital syphilis 1
• Do not use single-dose ceftriaxone therapy—it is not effective for treating syphilis 3
• Avoid azithromycin in the United States due to widespread resistance 1

Monitoring Errors

• Do not rely solely on treponemal test antibody titers to assess treatment response—they correlate poorly with disease activity 1
• Do not switch between different nontreponemal testing methods (e.g., VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 1
• Do not assume reactions lasting beyond 24 hours are JHR—they require alternative diagnosis 5

Follow-Up Errors

• Do not miss the 6-month follow-up for early syphilis—this is the critical timepoint for detecting treatment failure 1, 2
• Remember that 15-25% of successfully treated patients remain "serofast" with persistent low titers (<1:8) that do not indicate treatment failure 1