What is the recommended treatment for a 41-year-old male with a syphilis titer of 1:64, asymptomatic, and a history of syphilis and male-to-male intercourse?

Treatment Recommendation for Syphilis with History of Prior Infection

This patient requires benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at weekly intervals, because his titer of 1:64 with a history of prior syphilis indicates either late latent syphilis, syphilis of unknown duration, or possible treatment failure. 1

Critical Staging Determination

The key clinical challenge here is distinguishing between reinfection versus treatment failure versus inadequately treated prior infection:

• The titer of 1:64 is concerning because it exceeds the 1:32 threshold that some specialists use to recommend CSF examination, particularly in patients with a history of syphilis 1
• The negative test one year ago does not definitively establish this as early latent syphilis because you cannot confirm the exact timing of infection or whether prior "latent" titers represented adequate treatment 1
• Given the history of prior syphilis, this should be managed as late latent syphilis or syphilis of unknown duration to ensure adequate treatment 1

CSF Examination Considerations

You should strongly consider lumbar puncture before treatment in this patient based on multiple risk factors:

• Titer ≥1:32 with history of prior syphilis raises concern for possible neurosyphilis 1
• History of prior syphilis with unclear treatment adequacy 1
• MSM status with HIV risk (ensure HIV testing is performed) 1

If CSF examination shows abnormalities consistent with neurosyphilis, treat with aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days instead 1, 2

Treatment Protocol

Standard Regimen (if CSF normal or not performed)

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1
• This regimen is appropriate for late latent syphilis or syphilis of unknown duration 1

If Penicillin Allergic

• Doxycycline 100 mg orally twice daily for 28 days 1, 3
• Alternative: Tetracycline 500 mg orally four times daily for 28 days 1
• These alternatives require close serologic and clinical follow-up and have limited efficacy data 1, 4

Essential Concurrent Actions

HIV testing is mandatory because:

• MSM populations have high HIV prevalence 5
• HIV-infected patients require more intensive monitoring (every 3 months instead of 6 months) 1, 6
• HIV co-infection may affect treatment response, though single-dose therapy remains adequate for early syphilis in HIV-positive patients 7

Follow-Up Protocol

Quantitative nontreponemal serologic tests (RPR or VDRL) must be repeated at 6,12, and 24 months 1, 2

Treatment Failure Criteria

Re-treatment is indicated if:

• Titers increase fourfold at any point 1, 6
• Initial titer >1:32 fails to decline at least fourfold within 12-24 months 1, 6
• Clinical signs or symptoms develop 1, 6

If treatment failure occurs, perform CSF examination and re-treat with three weekly doses of benzathine penicillin G 2.4 million units IM (unless neurosyphilis is present) 6

Critical Pitfalls to Avoid

• Do not treat this as early latent syphilis with single-dose therapy given the uncertain duration and prior history 1
• Do not ignore the elevated titer (1:64) - this warrants consideration of CSF examination before treatment 1
• Do not assume the negative test one year ago rules out longer-standing infection - serologic responses can be delayed or atypical 1
• Do not use azithromycin - macrolide resistance in T. pallidum is widespread 8

Sex Partner Management

All sexual contacts within the past 90 days should be evaluated and treated presumptively 1