What is the alternative treatment (Rx) for penicillin in congenital syphilis?

From the Guidelines

The alternative treatment for congenital syphilis when penicillin cannot be used is ceftriaxone, administered at 75-100 mg/kg/day intravenously or intramuscularly for 10-14 days, as it is the most effective alternative with the best available evidence, although penicillin remains the gold standard treatment. This recommendation is based on the fact that ceftriaxone crosses the blood-brain barrier effectively and has demonstrated activity against Treponema pallidum, making it a suitable alternative in cases where penicillin is contraindicated due to severe allergic reactions 1.

Key Considerations

• Penicillin remains the first-line treatment for congenital syphilis due to its proven efficacy and safety profile.
• Desensitization to penicillin should be strongly considered before resorting to alternative treatments, especially in pregnant women, as it allows for the use of the most effective treatment available 1.
• Other antibiotics like macrolides (erythromycin, azithromycin) or doxycycline are not recommended for congenital syphilis due to inadequate central nervous system penetration, potential development of resistance, and insufficient data on efficacy.
• Close follow-up with serological testing at 3,6, and 12 months after treatment is essential to ensure adequate response to therapy regardless of the regimen used.

Evidence Review

The provided evidence from various studies 1 consistently indicates that no proven alternatives to penicillin are available for treating congenital syphilis, emphasizing the importance of penicillin as the primary treatment option. However, in cases where penicillin cannot be used, ceftriaxone emerges as a viable alternative based on its pharmacokinetic properties and efficacy against Treponema pallidum. The most recent and highest quality study 1 supports the use of ceftriaxone in such scenarios, guiding the recommendation for its use in clinical practice.

From the FDA Drug Label

Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.

• The alternative treatment for penicillin in congenital syphilis is not directly stated in the provided drug labels.
• However, for syphilis in general, doxycycline is recommended as an alternative treatment when patients are allergic to penicillin, with a dosage of 100 mg, twice a day for 2 weeks for early syphilis and 100 mg, twice a day for 4 weeks for syphilis of more than one year’s duration 2.
• It is essential to note that the provided drug labels do not specifically address congenital syphilis, and therefore, the recommended treatment may differ.
• A conservative clinical decision would be to consult additional resources or an expert in the field for the appropriate treatment of congenital syphilis in patients allergic to penicillin.

From the Research

Alternative Treatments for Penicillin in Congenital Syphilis

• Ceftriaxone has been suggested as a potential alternative therapy for the prevention of congenital syphilis when the mother is allergic to penicillin 3.
• Amoxicillin emerges as a potential oral candidate for the treatment of congenital syphilis, while ceftriaxone is considered a potential parenteral candidate 4.
• Other therapeutic alternatives include cefotaxime, ampicillin, doxycycline, cefixime, and linezolid 4.

Considerations for Alternative Treatments

• The use of alternative antibiotics for congenital syphilis is based on limited evidence, and more research is needed to determine the best route and timing of therapy 3, 4.
• Penicillin remains the first-line treatment for syphilis, and alternative treatments should only be considered in cases where penicillin is not suitable, such as in patients with significant penicillin allergies 5, 6.
• The emergence of Treponema pallidum resistant to macrolides, such as azithromycin, may limit options for patients with penicillin allergies and contribute to suboptimal treatment 6.

Current Recommendations

• The American Academy of Pediatrics (AAP) guidelines recommend the use of penicillin for the treatment of congenital syphilis, and alternative treatments should only be considered in consultation with a pediatric infectious disease specialist 3, 7.
• Pregnant patients with penicillin allergy should be desensitized and treated with penicillin to prevent congenital syphilis 6.