What is the recommended treatment for syphilis?

Treatment for Syphilis

Benzathine penicillin G administered intramuscularly is the definitive treatment for all stages of syphilis, with dosing determined by disease stage. 1, 2

Primary and Secondary Syphilis

Administer benzathine penicillin G 2.4 million units IM as a single dose. 1, 2

• This regimen achieves 90-100% treatment success rates for early syphilis 3
• For children with acquired primary or secondary syphilis, dose is 50,000 units/kg IM, up to the adult dose of 2.4 million units 2

Early Latent Syphilis

Give benzathine penicillin G 2.4 million units IM as a single dose. 1, 2

• Early latent syphilis is defined as infection acquired within the preceding year, documented by seroconversion, fourfold titer increase, history of symptoms, or having a sex partner with documented early syphilis 1

Late Latent Syphilis and Tertiary Syphilis

Administer benzathine penicillin G 7.2 million units total as 3 doses of 2.4 million units IM each at 1-week intervals. 1, 2

• If a dose is missed, an interval of 10-14 days between doses may be acceptable before restarting the sequence 1
• This applies to both late latent syphilis (or latent syphilis of unknown duration) and tertiary syphilis 1, 2

Neurosyphilis

Use aqueous crystalline penicillin G for neurosyphilis treatment. 1

• CSF examination is indicated for patients with neurological signs/symptoms, tertiary syphilis, or those whose serological titers fail to decline appropriately 1
• Neurosyphilis can occur at any stage and may cause meningitis, uveitis, hearing loss, or stroke 4

Penicillin-Allergic Patients (Non-Pregnant)

For primary and secondary syphilis: doxycycline 100 mg orally twice daily for 14 days. 1, 2

For late latent syphilis: doxycycline 100 mg orally twice daily for 28 days. 1, 2

Critical Caveat for Penicillin Allergy

• Pregnant women and neurosyphilis patients must receive penicillin regardless of allergy history - they should undergo desensitization followed by penicillin treatment, as penicillin is the only proven effective therapy for preventing maternal transmission and treating neurosyphilis 1, 2, 5
• Tetracyclines, doxycycline, and erythromycin are contraindicated in pregnancy due to hepatotoxicity, fetal bone/teeth staining, and failure to reliably cure fetal infection 5

Pregnancy-Specific Considerations

For primary, secondary, or early latent syphilis in pregnancy: benzathine penicillin G 2.4 million units IM in a single dose. 5

• Some specialists recommend a second dose of 2.4 million units IM one week after the initial dose, especially in the third trimester or for women with secondary syphilis or HIV infection 5

For late latent or latent syphilis of unknown duration in pregnancy: benzathine penicillin G 7.2 million units total as 3 doses of 2.4 million units IM each at weekly intervals. 5

• Up to 40% of fetuses with in-utero syphilis exposure are stillborn or die from infection during infancy if untreated 4
• All pregnant women should be screened for syphilis at the first prenatal visit, with high-risk populations requiring additional screening at 28-32 weeks gestation and at delivery 5
• Women should seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment due to potential Jarisch-Herxheimer reaction 5

HIV-Infected Patients

Use the same treatment regimens as for non-HIV-infected patients. 1, 2

• HIV-infected patients may have atypical serologic responses but generally respond well to standard treatment 1
• For pregnant women with HIV, consider a second dose of benzathine penicillin G 2.4 million units IM one week after the initial dose 5

Follow-Up and Monitoring

Repeat quantitative nontreponemal serologic tests (RPR or VDRL) at 3,6,12, and 24 months after treatment. 1

• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1, 2
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 2
• If treatment failure is suspected, re-evaluate for HIV infection and perform CSF examination 1
• For pregnant women, check serologic titers monthly until delivery to ensure adequate treatment response, and repeat titers in the third trimester and at delivery 5

Management of Sexual Partners

Persons exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative. 1, 2, 5

• Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 1, 2
• Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically 2, 5

Important Pitfalls to Avoid

• Do not use oral penicillin preparations - they are ineffective for syphilis treatment 1
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 1
• Do not switch between different testing methods (e.g., VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 1
• Do not delay treatment in pregnancy due to concerns about Jarisch-Herxheimer reaction causing stillbirth - untreated syphilis causes far greater fetal harm 5
• Do not discharge a newborn without documented maternal syphilis screening 5

Jarisch-Herxheimer Reaction

• An acute febrile reaction may occur within 24 hours after any syphilis therapy, especially in early syphilis, and may include headache, myalgia, and other symptoms 1
• Patients should be informed about this possible adverse reaction before treatment 1