What is the recommended treatment for a patient testing positive for syphilis?

Syphilis Treatment Recommendations

The recommended treatment for syphilis is benzathine penicillin G, with dosing dependent on the stage of infection: 2.4 million units IM as a single dose for primary, secondary, and early latent syphilis; or 7.2 million units total (administered as three doses of 2.4 million units IM at 1-week intervals) for late latent syphilis or syphilis of unknown duration. 1

Treatment by Stage

Primary, Secondary, and Early Latent Syphilis

• First-line treatment: Benzathine penicillin G 2.4 million units IM in a single dose 1
• Alternative for penicillin-allergic patients: Doxycycline 100 mg orally twice daily for 14 days 1, 2

Late Latent Syphilis or Syphilis of Unknown Duration

• First-line treatment: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
• Alternative for penicillin-allergic patients: Doxycycline 100 mg orally twice daily for 28 days 1, 2

Neurosyphilis

• First-line treatment: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
• Important note: Benzathine penicillin G is inadequate for treating neurosyphilis 3

Special Populations

Pregnant Women

• Only recommended treatment: Penicillin (appropriate to stage)
• Penicillin is the only proven effective treatment for syphilis during pregnancy 1
• If allergic to penicillin, desensitization is required 1

HIV-Infected Patients

• Same treatment regimens as HIV-negative patients but with closer follow-up 1

Treatment Monitoring and Follow-up

Serologic Testing

• Quantitative nontreponemal tests (RPR or VDRL) should be repeated at 6,12, and 24 months 1
• Treatment success indicators:
  • Primary/secondary syphilis: Fourfold decline in titers within 6 months 1
  • Latent/late syphilis: Fourfold decline in titers within 12-24 months 1, 4

Treatment Failure

Consider retreatment if:

• Titers increase fourfold
• Initially high titer fails to decline
• Signs or symptoms attributable to syphilis develop 1

Partner Management

• All sexual partners should be evaluated clinically and serologically 1
• Partners exposed within 90 days: Treat presumptively even if seronegative
• Partners exposed >90 days before diagnosis: Treat based on clinical and serological evaluation 1

Important Clinical Considerations

Penicillin Allergy Management

• For non-pregnant patients with penicillin allergy, doxycycline is the preferred alternative 1, 2
• For pregnant patients with penicillin allergy, desensitization is required 1

CSF Examination Indications

Perform CSF examination before treatment if:

• Neurologic or ophthalmic signs/symptoms present
• Evidence of active tertiary syphilis
• Treatment failure
• HIV infection 1

Current Challenges

• Benzathine penicillin G shortages have been reported, potentially complicating treatment 5
• If BPG is unavailable, alternative regimens may be necessary, but efforts should be made to secure BPG, especially for pregnant women 5

Cautions and Pitfalls

• Neurosyphilis requires IV penicillin treatment; benzathine penicillin G is ineffective for neurosyphilis 3
• Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment, requiring ongoing monitoring 1
• When administering benzathine penicillin G, either single or divided doses are equally well tolerated 6