What is the recommended treatment for a patient with a recent diagnosis of syphilis?

Treatment of Newly Diagnosed Syphilis

For a patient with a recent diagnosis of syphilis, administer benzathine penicillin G 2.4 million units intramuscularly as a single dose for primary, secondary, or early latent syphilis, or as three weekly doses (total 7.2 million units) for late latent or latent syphilis of unknown duration. 1

Initial Staging and Assessment

Before initiating treatment, determine the stage of syphilis infection:

• Primary syphilis: Painless anogenital chancre, typically diagnosed within weeks of exposure 2
• Secondary syphilis: Diffuse rash, mucocutaneous lesions, lymphadenopathy, or condyloma latum 1, 2
• Early latent syphilis: Asymptomatic infection acquired within the preceding year, documented by seroconversion, fourfold titer increase, recent symptoms, or partner with documented early syphilis 1
• Late latent syphilis: Asymptomatic infection acquired more than one year ago or of unknown duration 1

Perform a focused neurologic examination looking specifically for headache, vision changes, hearing loss, cranial nerve deficits, uveitis, or optic neuritis, as these mandate lumbar puncture before treatment 3. Test all patients for HIV infection, as HIV-positive patients may have atypical serologic responses and require more intensive monitoring 3, 1.

Treatment Regimens by Stage

Primary, Secondary, or Early Latent Syphilis

• Benzathine penicillin G 2.4 million units IM as a single dose 4, 1, 2
• This regimen achieves rapid elimination of clinical symptoms and promotes serologic response, with serum becoming negative within 1 year for primary syphilis and within 2 years for secondary syphilis 5

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units) 3, 1
• If a dose is missed, an interval of 10-14 days between doses is acceptable before restarting the sequence 1

Neurosyphilis (Any Stage)

• Aqueous crystalline penicillin G 18-24 million units per day IV (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days 1

Penicillin Allergy Management

Pregnant women and patients with neurosyphilis who report penicillin allergy MUST undergo desensitization followed by penicillin treatment, as penicillin is the only therapy with documented efficacy for preventing maternal transmission and treating neurosyphilis. 4, 1

For non-pregnant adults without neurosyphilis:

• Primary, secondary, or early latent syphilis: Doxycycline 100 mg orally twice daily for 14 days 1, 6
• Late latent syphilis: Doxycycline 100 mg orally twice daily for 28 days 1, 6

Critical caveat: Azithromycin should NOT be used in the United States due to widespread macrolide resistance and documented treatment failures 1. Ceftriaxone 1 gram IV/IM daily for 10 days is a reasonable alternative based on randomized trial data, though less commonly used 1.

Management of Sex Partners

• Persons exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 4, 1
• Persons exposed more than 90 days before diagnosis should be treated presumptively if serologic results are not immediately available and follow-up is uncertain 4, 1
• Time periods for identifying at-risk partners: 3 months plus duration of symptoms for primary syphilis, 6 months plus duration of symptoms for secondary syphilis, and 1 year for early latent syphilis 4, 1

Follow-Up Protocol

• Obtain quantitative nontreponemal serologic tests (RPR or VDRL) at 6 and 12 months after treatment for primary/secondary syphilis 1
• For latent syphilis, repeat quantitative nontreponemal tests at 6,12, and 24 months 3, 1
• Expected response: Fourfold decline in titers within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
• HIV-infected patients require more frequent monitoring at 3-month intervals instead of 6-month intervals 3, 1

Use the same nontreponemal test (RPR or VDRL) by the same laboratory for all follow-up testing, as results cannot be directly compared between different testing methods 1.

Important Clinical Considerations

Jarisch-Herxheimer Reaction

• An acute febrile reaction often accompanied by headache and myalgia may occur within 24 hours after any syphilis therapy, particularly in early syphilis 4, 1
• Advise patients of this possible adverse reaction; antipyretics may be recommended 4
• In pregnant women, this reaction may precipitate premature labor or fetal distress during the second half of pregnancy, but this concern should not prevent or delay therapy 4, 1
• Women should seek immediate medical attention if they notice changes in fetal movements or contractions after treatment 1

Treatment Failure Criteria

Re-treat and evaluate for HIV if any of the following occur:

• Persistent or recurring signs/symptoms 1
• Sustained fourfold increase in nontreponemal titers 1, 7
• Failure of initially high titer to decline at least fourfold within 6 months for early syphilis or 12-24 months for late syphilis 1, 7

If treatment failure is suspected, perform lumbar puncture to evaluate for neurosyphilis unless reinfection is certain 7.