What is the recommended treatment for latent syphilis?

Treatment for Latent Stage Syphilis

For early latent syphilis (duration <1 year), treat with benzathine penicillin G 2.4 million units IM as a single dose; for late latent syphilis or latent syphilis of unknown duration, treat with benzathine penicillin G 7.2 million units total administered as three doses of 2.4 million units IM at weekly intervals. 1

Treatment Algorithm by Stage

Early Latent Syphilis (Duration <1 Year)

• Benzathine penicillin G 2.4 million units IM in a single dose is the recommended first-line treatment 1
• Early latent syphilis is diagnosed when patients have documented seroconversion, unequivocal symptoms of primary or secondary syphilis within the past year, or a sex partner with documented early syphilis 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals 1
• If a patient misses a dose during weekly therapy, an interval of 10-14 days between doses may be acceptable before restarting the sequence, though this is not acceptable for pregnant patients who must repeat the full course 1

Pre-Treatment Evaluation

CSF Examination Indications

Perform lumbar puncture before treatment if the patient has any of the following criteria:

• Neurologic or ophthalmic signs or symptoms 1
• Evidence of active tertiary syphilis (aortitis, gumma, iritis) 1
• Treatment failure 1
• HIV infection with late latent syphilis or syphilis of unknown duration 1
• Serum nontreponemal titer ≥1:32, unless duration of infection is known to be <1 year 1
• Nonpenicillin therapy planned, unless duration is known to be <1 year 1

If CSF shows abnormalities consistent with neurosyphilis, treat as neurosyphilis with aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days 1

Additional Baseline Assessment

• All patients with latent syphilis should be evaluated clinically for tertiary disease manifestations 1
• All syphilis patients must be tested for HIV 1

Alternative Regimens for Penicillin Allergy

Non-Pregnant Patients

Only use alternative regimens after CSF examination has excluded neurosyphilis 1

• Early latent syphilis: Doxycycline 100 mg orally twice daily for 14 days OR tetracycline 500 mg orally four times daily for 14 days 1, 2
• Late latent syphilis or unknown duration: Doxycycline 100 mg orally twice daily for 28 days OR tetracycline 500 mg orally four times daily for 28 days 1, 2

Critical caveat: The effectiveness of non-penicillin alternatives has not been well documented, and these therapies should be used only with close serologic and clinical follow-up 1

Pregnant Patients

Pregnant patients allergic to penicillin must be desensitized and treated with penicillin - there are no acceptable alternatives 1

Follow-Up Protocol

Serologic Monitoring

• Repeat quantitative nontreponemal serologic tests at 6,12, and 24 months after treatment 1
• For HIV-infected patients, some experts recommend monitoring at 3-month intervals instead of 6-month intervals 3

Treatment Failure Criteria

Re-treat the patient if any of the following occur:

• Titers increase fourfold (e.g., from 1:8 to 1:32) 1
• An initially high titer (≥1:32) fails to decline at least fourfold within 12-24 months 1
• Signs or symptoms attributable to syphilis develop 1

When treatment failure occurs, evaluate for neurosyphilis with CSF examination and re-treat appropriately 1

Pediatric Considerations

Pre-Treatment Assessment

• After the newborn period, children diagnosed with syphilis should have CSF examination to exclude neurosyphilis 1
• Review birth and maternal medical records to assess whether the child has congenital or acquired syphilis 1

Pediatric Dosing

• Early latent syphilis: Benzathine penicillin G 50,000 units/kg IM (up to adult dose of 2.4 million units) in a single dose 1
• Late latent syphilis or unknown duration: Benzathine penicillin G 50,000 units/kg IM (up to 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) 1

Common Pitfalls and Caveats

• Do not confuse latent syphilis with neurosyphilis: Standard latent syphilis regimens may not be optimal for asymptomatic neurosyphilis, which requires IV penicillin 1
• Doxycycline is not adequate for neurosyphilis - patients with CNS involvement require IV aqueous crystalline penicillin G regardless of penicillin allergy status 3
• The efficacy of alternative regimens (doxycycline, tetracycline) in HIV-infected persons has not been studied and must be considered with caution 1
• In rare instances, despite negative CSF examination and repeated therapy, serologic titers may still not decline - the need for additional therapy or repeated CSF examinations in these circumstances is unclear 1