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Background Maternal syphilis leads to preventable adverse fetal health outcomes. The recommended treatment is benzathine penicillin, which is challenging due to shortages, drug allergies and inability to administer the injection. We conducted a literature review to identify potential treatment options for maternal syphilis. Methods We searched PubMed, Embase, and Scopus from January 1, 1970 to December 31, 2018. The search terms “syphilis” AND (“maternal” OR “pregnancy” OR “congenital”), AND “treatment” NOT (“screening”) were used. Additional articles were identified from the references. We included studies in English, with full text, on humans and women. Successful treatment was defined as maternal RPR titer decline and congenital syphilis prevention. Results Of the 70 articles, 8 case series were included. 11 pregnant women were successfully treated with intramuscular ceftriaxone 250 mg: 7-day course for primary syphilis or 10-day course for secondary syphilis, repeated at 28-weeks gestation. One patient was successfully treated with amoxicillin 6g and probenecid 1g daily for 14 days, and another was successfully treated with a 6-day course of amoxicillin followed by ceftriaxone 2g intravenously for 8 days. In response to ampicillin 2g intravenously intrapartum, one mother and one neonate developed the Jarish-Herxheimer reaction in cases of undiagnosed syphilis. Macrolides failed to prevent congenital syphilis: 5 patients treated with azithromycin 1g orally for 1–10 days, one case report of erythromycin 750 mg orally QID for 12 days and one case report of two failed 15-day courses of oral erythromycin 750–800 mg QID until penicillin desensitization was initiated. One case of clindamycin decreased maternal RPR titers, but failed to prevent congenital syphilis. Conclusion Overall, 23 patients were treated with penicillin alternatives (15 with beta-lactam antibiotics, 7 with macrolide antibiotics, 1 with clindamycin), and 13 were treated successfully. Clinical research should evaluate amoxicillin and cephalosporins. Our review does not support the use of macrolide antibiotics. Disclosure No significant relationships.

Background Increasing incidence of syphilis in the United States and penicillin shortages internationally call for research on alternative treatment options. In this randomized, multisite, open-label, non-comparative clinical trial, we are evaluating the efficacy of cefixime as treatment of early syphilis. Methods Eligible participants are 18 years or older, have laboratory confirmed early syphilis (new Rapid Plasma Reagin [RPR] titer ≥1:8 or 4-fold titer rise in past 12 months), and no concomitant antibiotic use. Patients with HIV infection must have undetectable viral load in the past 12 months and CD4+ count ≥350 cells/μl. Participants were randomized to receive either 2.4M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day, for ten days. Participants return for follow-up at 3, 6, and 12 months post-treatment for laboratory testing. The main outcome is a 4-fold RPR titer decrease at 6 months post-treatment. Results To date, 27 participants (15 penicillin, 12 cefixime) are enrolled. The majority of the study population is men (26/27), Latino (15/27), and HIV-infected (25/27). Eight participants completed their 3-month follow up (4 cefixime/4 penicillin). In the cefixime arm, 3/4 participants had an equal or greater than four-fold decrease in the RPR titer, and 1/4 had a two-fold decrease. In the penicillin arm, 2/4 participants had an equal or greater than 4-fold decrease in the RPR titer, 1/4 had a two-fold decrease, and 1/4 is missing data. Conclusion Enrollment is still open and data collection ongoing. Initial results are encouraging. Disclosure No significant relationships.