Treatment for Late Latent Syphilis
The recommended dose for treating late latent syphilis is benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1-week intervals. 1, 2
Dosing Regimen Details
Adults with late latent syphilis or latent syphilis of unknown duration:
Children with late latent syphilis:
- 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 the adult total dose of 7.2 million units 2
Timing Considerations
- If a patient misses a dose in the weekly therapy schedule:
- Pharmacologic considerations suggest that an interval of 10-14 days between doses might be acceptable before restarting the sequence 2, 3
- Some evidence suggests that an interval of 7-9 days between doses may be more optimal if feasible 3
- Important caveat: Missed doses are never acceptable for pregnant women, who must repeat the full course of therapy if any dose is missed 2, 1
Alternative Treatments for Penicillin-Allergic Patients
For non-pregnant patients with penicillin allergy:
- Doxycycline 100 mg orally twice daily for 28 days 1
- Preferred over tetracycline due to better compliance and fewer gastrointestinal side effects
Special Considerations
CSF Examination
A CSF examination should be performed before treatment if any of the following are present:
- Neurologic or ophthalmic signs or symptoms
- Evidence of active tertiary syphilis (e.g., aortitis, gumma, iritis)
- Treatment failure
- HIV infection with late latent syphilis or syphilis of unknown duration
- Some specialists recommend CSF examination for patients with nontreponemal serologic test titers >1:32 2, 1
Treatment Monitoring
- Quantitative nontreponemal serologic tests (RPR or VDRL) should be repeated at 6,12, and 24 months 1
- Treatment success is indicated by a fourfold decline in titers within 12-24 months for late latent syphilis 1
- Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment 1
Clinical Challenges
- Recent data shows low completion rates for the full three-dose regimen, with only 42.9% of patients receiving all three injections within the recommended timeframe 4
- Pregnant women have higher completion rates (68.7%), likely due to increased monitoring 4
- Benzathine penicillin G shortages have been reported, potentially complicating treatment access 5
- Emerging research is investigating subcutaneous infusion of high-dose BPG as a potential single-dose alternative for late latent syphilis, but this is not yet standard practice 6
The three-dose regimen remains the gold standard treatment for late latent syphilis despite these challenges, as it ensures adequate treatment for potentially long-standing infections that might otherwise progress to tertiary complications 1.