What treatment is recommended for a patient with syphilis and a beta-lactam allergy?

Treatment for Syphilis in Patients with Beta-Lactam Allergy

For patients with syphilis and beta-lactam allergy, doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) is the recommended alternative treatment. 1, 2

Treatment Algorithm Based on Disease Stage

Early Syphilis (Primary, Secondary, Early Latent < 1 year)

• First choice: Doxycycline 100 mg orally twice daily for 14 days 3, 1, 2
• Alternative: Tetracycline 500 mg orally four times daily for 14 days 3, 4

Late Syphilis (Late Latent > 1 year or Unknown Duration)

• First choice: Doxycycline 100 mg orally twice daily for 28 days 3, 1
• Alternative: Tetracycline 500 mg orally four times daily for 28 days 3, 4

Special Considerations

Neurosyphilis

• Important: CSF examination must be performed to exclude neurosyphilis before using non-penicillin therapy 3
• If neurosyphilis is present, penicillin desensitization followed by appropriate penicillin treatment is necessary 1

Pregnancy

• Pregnant patients with penicillin allergy should undergo penicillin desensitization followed by standard penicillin treatment 3, 1, 5
• Doxycycline and tetracycline are contraindicated in pregnancy

HIV Co-infection

• Same regimens apply, but more intensive monitoring is required 1
• Clinical and serological evaluation at 3 and 6 months after treatment 1

Efficacy of Alternative Treatments

Doxycycline has demonstrated comparable efficacy to penicillin in treating early syphilis. A study comparing doxycycline with benzathine penicillin G found no serological failures in the doxycycline group (0%; 95% CI, 0%-10.3%) compared to 5.5% (95% CI, 1.6%-13.8%) in the penicillin group 6.

However, a systematic review and network meta-analysis found that while serological response rates were similar between penicillin, doxycycline/tetracycline, and ceftriaxone, the treatment failure rate was significantly lower among penicillin recipients than among doxycycline/tetracycline recipients (RR = 0.58,95% CI 0.38-0.89) 7.

Follow-Up Recommendations

• Quantitative nontreponemal serologic tests should be repeated at 6 months and 12 months 3
• Treatment success is defined as a four-fold decrease in non-treponemal test titers within 12-24 months 1
• If titers increase fourfold, or if an initially high titer (≥1:32) fails to decline at least fourfold within 12-24 months, or if the patient develops new signs or symptoms, evaluate for neurosyphilis and retreat 3

Common Pitfalls and Caveats

1. Never use other beta-lactams (e.g., cephalosporins) in patients with severe penicillin allergy due to potential cross-reactivity 5

2. CSF examination is mandatory before using non-penicillin therapy in patients with:

   • Late syphilis
   • Neurological symptoms
   • HIV co-infection
   • Treatment failure 3, 1

3. Medication adherence is critical with multi-dose oral regimens like doxycycline and tetracycline

4. Absorption interference: Doxycycline absorption is not markedly influenced by food or milk 2, but tetracycline absorption is impaired by antacids containing aluminum, calcium, magnesium, iron, zinc, sodium bicarbonate, and some dairy products 4

5. All patients with syphilis should be tested for HIV 3, 1