What is the most appropriate medication for a 25-year-old male with a painless ulcer on his penis, likely syphilis, and an allergy to beta-lactam (penicillin) antibiotics?

Treatment of Primary Syphilis in a Patient with Beta-Lactam Allergy

For a 25-year-old male with a painless penile ulcer consistent with primary syphilis who has a beta-lactam allergy, doxycycline 100 mg orally twice daily for 14 days is the most appropriate treatment.

Clinical Presentation Analysis

The patient presents with classic signs of primary syphilis:

• Painless ulcer (chancre) on penis for 2 days
• Indurated, nontender lesion
• Enlarged, nontender inguinal lymph nodes
• Recent unprotected sexual encounter with new partner
• No dysuria, urethritis, or penile discharge

Treatment Options for Penicillin-Allergic Patients

First-Line Alternative Treatment

• Doxycycline 100 mg orally twice daily for 14 days 1, 2
  • FDA-approved for treatment of primary syphilis in penicillin-allergic patients
  • Complete 14-day course is essential for eradication of infection
  • Has demonstrated efficacy comparable to benzathine penicillin G in clinical studies 3

Alternative Options (Less Preferred)

• Tetracycline 500 mg orally four times daily for 14 days 4

  • Effective but less convenient dosing schedule
  • Higher risk of gastrointestinal side effects
  • Lower compliance rates compared to doxycycline 4

• Erythromycin 500 mg orally four times daily for 14 days 4

  • Less effective than doxycycline or tetracycline
  • Only recommended if patient cannot tolerate tetracyclines
  • Requires strict compliance monitoring

• Ceftriaxone (various regimens) 4

  • Limited clinical data on efficacy
  • Risk of cross-reactivity in patients with penicillin allergy
  • No standardized dosing regimen established

Follow-Up Recommendations

1. Clinical and serological evaluation at 3 and 6 months 4, 1
2. Treatment success defined as four-fold decrease in non-treponemal test titers 1
3. HIV testing should be performed 4, 1
4. Partner notification and treatment 4, 1

Important Considerations

• Doxycycline has been shown to have comparable efficacy to penicillin in treating early syphilis with no serological failures in comparative studies 3
• For patients with severe penicillin allergy who cannot tolerate doxycycline, desensitization to penicillin followed by standard penicillin treatment should be considered 4
• Single-dose therapies (like single-dose ceftriaxone) are not effective for treating syphilis 4
• Compliance with the full 14-day course is critical for treatment success 1

Common Pitfalls to Avoid

1. Using inadequate duration of therapy (full 14 days required)
2. Failing to test for HIV co-infection
3. Inadequate follow-up serological testing
4. Not treating sexual partners exposed within 90 days
5. Assuming cephalosporins are safe in all penicillin-allergic patients (cross-reactivity risk)

In this case, doxycycline provides the optimal balance of efficacy, safety, and compliance for a penicillin-allergic patient with primary syphilis.