(P22) CONGENITAL SYPHILIS – COMPREHENSIVE REVIEW OF ALTERNATIVE ANTIBIOTIC TREATMENT FOR USE IN NEONATES

Background:
Congenital syphilis rates increased 10-fold from 2012 to 2022 in the United States. Currently, the therapeutic standard of care is 10 days of intravenous (IV) aqueous crystalline penicillin G, with very limited evidence for alternatives. A long course of IV antibiotic requires hospitalization that is both costly and burdensome for the child and the family. Fortunately, T. pallidum retains susceptibility to other antibiotics based on minimum inhibitory concentrations (MICs).

Methods:
There are no randomized controlled studies comparing the treatment of congenital syphilis by antibiotics, both intravenous and oral formulations, other than penicillin. We conducted a comprehensive review of current literature to identify alternative antibiotic treatments for use in neonates. The development of an appropriate culture system has allowed for susceptibility testing of T. pallidum using different antimicrobial agents. T. pallidum remains exquisitely sensitive to penicillin, but it has also shown susceptibility to other generations of penicillin, cephalosporins, tetracyclines, oxazolidinones, and macrolides. Treponemal MICs have been calculated for multiple different antibiotics. We focused on antibiotics shown to have favorable MICs for T. pallidum in vitro. We then reviewed clinical trials using alternative antibiotics for syphilis and neurosyphilis in adults, with simultaneous consideration of the known safety profile for neonates and efficacy for neonatal infections and CNS penetration.

Results:
Based on the evidence of safety and efficacy of different antibiotics for use in neonates, ceftriaxone emerges as a potential parenteral candidate and amoxicillin emerges as a potential oral candidate for the treatment of congenital syphilis. Other therapeutic alternatives include cefotaxime (where available), ampicillin, doxycycline, cefixime, and linezolid.

Conclusion:
Based on the known pharmacokinetic information for these antibiotics, creating a pharmacokinetic model and therapeutic simulation to determine the best dosage and frequency may be the best next step in expanding the repertoire of available therapeutic options.