Treatment of Primary Syphilis in a Penicillin-Allergic Patient
For this non-pregnant patient with primary syphilis and beta-lactam allergy, doxycycline 100 mg orally twice daily for 14 days is the most appropriate treatment. 1, 2
Clinical Presentation Confirms Primary Syphilis
The clinical picture is classic for primary syphilis:
- Painless, indurated ulcer (chancre) on the penis with recent unprotected sexual contact strongly suggests Treponema pallidum infection 2
- Nontender, enlarged inguinal lymphadenopathy is characteristic of primary syphilis 2
- The absence of dysuria, urethritis, or discharge makes other sexually transmitted infections less likely 2
Why Penicillin Cannot Be Used
- Penicillin G benzathine 2.4 million units IM as a single dose is the first-line treatment for primary syphilis, but this patient has a documented beta-lactam allergy 2, 3
- Cefixime (option a) is contraindicated because cephalosporins are beta-lactams and cross-reactivity exists, particularly in patients with severe beta-lactam allergies 1
- In non-pregnant patients with beta-lactam allergy, desensitization is not routinely required—alternative antibiotics are acceptable 1
Doxycycline is the Preferred Alternative
The CDC explicitly recommends doxycycline 100 mg orally twice daily for 14 days as the preferred alternative for non-pregnant, penicillin-allergic patients with primary or secondary syphilis 1, 2, 4
Key advantages of doxycycline:
- Better compliance than tetracycline due to twice-daily dosing versus four times daily 1
- Proven efficacy in treating early syphilis in penicillin-allergic patients 2, 5
- Well-tolerated with predictable pharmacokinetics 4
Why Other Options Are Inferior
Erythromycin (option c)
- Erythromycin is explicitly noted as "less effective than other recommended regimens" by the CDC 1
- Should only be considered when compliance can be assured and doxycycline cannot be tolerated 1
- The FDA label indicates erythromycin is an "alternative choice" for penicillin-allergic patients, but guidelines clearly favor doxycycline 6
Valacyclovir (option e)
- Valacyclovir has no role in syphilis treatment—it is an antiviral for herpes simplex virus 2
- While herpes can cause genital ulcers, this patient's painless, indurated ulcer with lymphadenopathy is pathognomonic for syphilis, not herpes 2
Critical Follow-Up Requirements
After initiating doxycycline therapy:
- Clinical and serologic evaluation at 6 and 12 months using quantitative nontreponemal tests (RPR or VDRL) 2, 3
- Treatment success is defined by a fourfold decline in nontreponemal titers within 6 months for primary syphilis 2, 3
- HIV testing is mandatory for all patients with syphilis, as HIV co-infection may affect treatment response 7, 2
- Partner notification and treatment is essential to prevent reinfection 1
Important Clinical Caveats
- Jarisch-Herxheimer reaction (acute fever, headache, myalgia within 24 hours) may occur with any syphilis treatment, including doxycycline 7, 2
- Ensure compliance counseling: The 14-day course must be completed for treatment success 1, 4
- Avoid doxycycline in pregnancy: Pregnant patients with penicillin allergy require desensitization and penicillin treatment, as no alternatives are proven safe for preventing congenital syphilis 1, 8
- Lab results pending: While awaiting confirmatory testing (darkfield microscopy or treponemal tests), empiric treatment should not be delayed given the high clinical suspicion 2, 5
Answer: b. doxy