Expanding treatment options for syphilis during pregnancy: a review of alternatives to penicillin



Townsend, CL, Mofenson, L, Gottlieb, S, Peters, RPH, Mitjà, O, Pérez-Mañá, C, Abrams, EJ, Delany-Moretlwe, S, Lockman, S, Waitt, C ORCID: 0000-0003-0134-5855
et al (show 3 more authors) (2026) Expanding treatment options for syphilis during pregnancy: a review of alternatives to penicillin Frontiers in Global Women S Health, 7. 1879243-. ISSN 2673-5059, 2673-5059

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Abstract

Syphilis infection during pregnancy leads to around 390, 000 adverse birth outcomes each year and is an important cause of preventable stillbirth. Although benzathine penicillin G is safe and effective during pregnancy for treating maternal and fetal infection, there are frequent global shortages and limited options for people with penicillin allergy. We conducted a review of potential alternatives to penicillin for treating syphilis during pregnancy when penicillin is not available or cannot be used, including ceftriaxone, amoxicillin, doxycycline, cefixime, and linezolid. Despite some efficacy data on their use in non-pregnant adults with syphilis, limited data were available on placental transfer, pharmacokinetics and dosing, efficacy or effectiveness, and safety in pregnancy. Given its favourable preclinical reproductive toxicity data, efficacy data in non-pregnant adults with syphilis, and safety during pregnancy when used for other indications, ceftriaxone could potentially be considered as an alternative treatment for pregnant women with syphilis in cases where penicillin cannot be used, as currently recommended by the World Health Organization. However, evidence about optimal dosing, feasibility, and efficacy/effectiveness for treating syphilis during pregnancy is needed. Several planned and ongoing clinical trials will provide additional data to inform the use of cefixime, amoxicillin, and linezolid in pregnant women with syphilis. Going forward, evaluation of new and existing medications for treating syphilis and preventing congenital syphilis should include a pregnancy investigation plan. Where possible, efforts should be made to ensure that high-quality pregnancy safety and efficacy or effectiveness data on drug candidates are generated in carefully designed studies to ensure that pregnant women and their infants are able to benefit from the full range of treatment options.

Item Type: Article
Uncontrolled Keywords: pregnancy, review, safety, syphilis, therapeutics, treatment
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff)
Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Women's & Children's Health
Depositing User: Symplectic Admin
Date Deposited: 01 Sep 2026 08:35
Last Modified: 28 Sep 2026 05:58
DOI: 10.3389/fgwh.2026.1879243
Open Access URL: https://www.frontiersin.org/journals/global-womens...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3200161
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