What is the appropriate treatment for a patient with late latent syphilis, as indicated by positive RPR and TPHA results without evidence of neurosyphilis?

Treatment for Late Latent Syphilis Without Neurosyphilis

This 68-year-old HIV-negative patient with late latent syphilis (positive RPR 1:128, positive TPHA, negative CSF findings) should be treated with benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at weekly intervals. 1

Rationale for Treatment Decision

The clinical presentation confirms late latent syphilis without neurosyphilis based on:

• Positive serologic tests (RPR 1:128 and TPHA 1:20) indicating treponemal infection 1
• Normal CSF examination (nil white cells, negative CSF VDRL) excluding neurosyphilis 1
• HIV-negative status, which simplifies the treatment approach 1

The standard three-dose regimen of benzathine penicillin G is the definitive treatment for late latent syphilis or syphilis of unknown duration in non-allergic patients with normal CSF examination. 1

Treatment Protocol

Primary Regimen

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1
• Each injection can be given as a single 2.4 million unit dose or divided into two 1.2 million unit injections (one in each buttock) with equal tolerability 2
• Administer adequate fluids with any oral medications to reduce esophageal irritation risk 3

Alternative Regimens (Penicillin Allergy Only)

If the patient has documented penicillin allergy:

• Doxycycline 100 mg orally twice daily for 28 days 1, 3
• Tetracycline 500 mg orally four times daily for 28 days 1
• These alternatives require close serologic and clinical follow-up due to less robust efficacy data 1

Critical Considerations

Why CSF Examination Was Appropriate

The CDC guidelines recommend CSF examination in specific circumstances, and this patient met criteria due to the high RPR titer (1:128, which exceeds 1:32) 1. Some specialists recommend CSF examination for all patients with latent syphilis and nontreponemal titers >1:32, though the risk of neurosyphilis in this circumstance remains uncertain 1.

Missed Dose Management

If the patient misses a weekly dose during the three-week treatment course:

• An interval of 10-14 days between doses may be acceptable before restarting the sequence 1
• However, this flexibility does not apply to pregnant patients, who must repeat the full course if any dose is missed 1

Follow-Up Protocol

Serologic Monitoring

Repeat quantitative nontreponemal tests (RPR) at 6,12, and 24 months after treatment completion. 1, 4

Treatment Failure Criteria

Re-treatment for latent syphilis is indicated if:

• Titers increase fourfold at any point 1
• An initially high titer (>1:32) fails to decline at least fourfold (two dilutions) within 12-24 months 1
• Signs or symptoms attributable to syphilis develop 1

If treatment failure occurs, perform CSF examination before re-treatment to exclude neurosyphilis 1.

Common Pitfalls to Avoid

High Titer Considerations

This patient's RPR titer of 1:128 is notably elevated. While the CSF examination was negative, close monitoring is essential as some specialists consider titers >1:32 to carry uncertain neurosyphilis risk 1. The patient should be counseled about neurologic or ophthalmic symptoms that would warrant immediate re-evaluation 1, 4.

Serofast State

In rare instances, despite negative CSF examination and repeated therapy, serologic titers may not decline as expected. This "serofast" state does not necessarily indicate treatment failure, and the need for additional therapy or repeated CSF examinations in this scenario remains unclear 1.

HIV Testing

Although this patient is HIV-negative, all syphilis patients should be tested for HIV, as co-infection significantly alters treatment response monitoring and follow-up requirements 4, 5.