Approach to managing syphilis during pregnancy

Manage pregnant patients with syphilis in consultation with an expert.

Treatment of syphilis in pregnant patients is with penicillin as recommended for nonpregnant patients; seeEppes, 2022Rac, 2017Roberts, 2019:

Note: Penicillin is the only treatment known to be effective in preventing congenital syphilis.

Penicillin is the only treatment known to be effective in preventing congenital syphilisEppes, 2022Rac, 2017Stafford, 2024Workowski, 2021. For patients who report penicillin hypersensitivity, verify their allergy. In some patients it may be appropriate to directly delabel their allergy by taking an extensive allergy history (see Clinical history for initial assessment of patients reporting penicillin hypersensitivity); in these patients benzathine benzylpenicillin should be used.

Seek expert advice (eg from an infectious diseases physician or clinical microbiologist) for patients with a verified allergy. For patients who have had a nonsevere (immediate or delayed) or a severe (immediate)1 hypersensitivity reaction to a penicillin, desensitisation may be an option.

For patients who have had a severe (delayed)2 hypersensitivity reaction to a penicillin, desensitisation should not be performed – seek expert advice for alternative treatment.

Doxycycline is not recommended for treatment of syphilis in pregnancy because of safety concerns and a lack of data on effectiveness in preventing congenital syphilis. Azithromycin resistance in Treponema pallidum is widespread so azithromycin should not be used; erythromycin and azithromycin have failed to prevent congenital syphilisBritish Association for Sexual Health and HIV (BASHH), 2019Rac, 2017Read, 2014Roberts, 2019Stamm, 2015Workowski, 2021. There are insufficient data to recommend cephalosporins for treatment of syphilis in pregnancy and prevention of congenital syphilisRac, 2017Roberts, 2019Workowski, 2021.

Treatment for early syphilis during the second half of pregnancy carries a risk of premature labour and fetal compromise if treatment precipitates a Jarisch–Herxheimer reaction (see Approach to managing syphilis for more information)Eppes, 2022Rac, 2017Workowski, 2021. Advise pregnant patients to seek urgent obstetric review if they notice fever, contractions or a reduction in fetal movementAustralian Society for Infectious Diseases (ASID), 2022Eppes, 2022Stafford, 2024Workowski, 2021.

If syphilis is diagnosed during the second half of pregnancy, perform an ultrasound to evaluate the fetus for signs of congenital syphilis. Do not delay antibiotic therapy to perform the ultrasound. The risk of treatment failure in the fetus is higher if the ultrasound shows fetal hepatomegaly, ascites, hydrops, polyhydramnios, fetal anaemia or placental thickening – seek expert adviceEppes, 2022Rac, 2017Workowski, 2021.

1 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return
2 Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).Return