Abstract
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 aqueous crystalline penicillin G, with very limited evidence for alternatives. A long course of intravenous antibiotic requires hospitalization that is both costly and burdensome for the child and the family. Fortunately, Treponema pallidum retains susceptibility to other antibiotics based on minimum inhibitory concentrations. 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.