What is the treatment for syphilis (Treponema pallidum infection) in pregnancy?

From the Guidelines

Penicillin G is the recommended treatment for syphilis during pregnancy, with a single intramuscular injection of benzathine penicillin G 2.4 million units for early syphilis and three weekly injections for late latent syphilis or syphilis of unknown duration. This recommendation is based on the most recent and highest quality evidence, which emphasizes the importance of treating syphilis in pregnancy to prevent vertical transmission to the fetus and reduce the risk of congenital syphilis, which can cause severe complications including stillbirth, prematurity, and long-term neurological and developmental problems in the infant 1.

Key Considerations

• Pregnant women with penicillin allergy should undergo desensitization followed by penicillin treatment, as alternative antibiotics may not effectively cross the placenta to treat fetal infection 1.
• After treatment, follow-up serologic testing is essential at 1,3,6, and 12 months to ensure adequate response 1.
• The Jarisch-Herxheimer reaction, characterized by fever, chills, headache, and myalgia, may occur within 24 hours of treatment and can potentially trigger preterm labor, so pregnant women should be monitored closely 1.
• Penicillin remains the gold standard because it effectively crosses the placenta and treats both maternal infection and prevents congenital syphilis 1.

Treatment Regimens

• For early syphilis (primary, secondary, or early latent), a single intramuscular injection of benzathine penicillin G 2.4 million units is the standard treatment.
• For late latent syphilis or syphilis of unknown duration, three weekly injections of benzathine penicillin G 2.4 million units are required.
• Some evidence suggests that additional therapy can be beneficial for pregnant women in some settings, such as a second dose of benzathine penicillin 2.4 million units IM administered 1 week after the initial dose for women who have primary, secondary, or early latent syphilis 1.

From the FDA Drug Label

Syphilis in Pregnancy There have been reports suggesting that erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with oral erythromycin for early syphilis should be treated with an appropriate penicillin regimen

Treatment of syphilis in pregnancy with erythromycin is not recommended as it may not reach the fetus in adequate concentration to prevent congenital syphilis.

• Infants born to women treated with erythromycin during pregnancy should be treated with an appropriate penicillin regimen. 2

From the Research

Treatment of Syphilis in Pregnancy

• The only recommended treatment for syphilis in pregnancy is benzathine penicillin G, as evidence of decreased risk of congenital syphilis with other modalities is lacking 3, 4, 5, 6.
• Benzathine penicillin G should be administered according to maternal stage of infection per Centers for Disease Control and Prevention guidelines 4.
• Women with a penicillin allergy should be desensitized and then treated with penicillin appropriate for their stage of syphilis 4.
• The Jarisch-Herxheimer reaction occurs in up to 44% of gravidas and can cause contractions, fetal heart rate abnormalities, and even stillbirth in the most severely affected pregnancies 4.
• It is recommended that all viable pregnancies receive the first dose of benzathine penicillin G in a labor and delivery department under continuous fetal monitoring for at least 24 hours 4.

Testing for Syphilis in Pregnancy

• Testing for syphilis is complex and includes either the reverse-sequence algorithm or the traditional algorithm 3.
• Determination of the clinical stage of syphilis includes incorporation of the previous treatment sequence and physical examination 3.
• Women testing positive for syphilis should undergo a history and physical exam as well as testing for other sexually transmitted infections, including HIV 4.
• Testing should be performed at initiation of prenatal care and twice during the third trimester in high-risk patients 4.

Prevention of Congenital Syphilis

• Congenital syphilis can lead to stillbirth, miscarriage, preterm birth, birth defects, and lifelong physical or neurologic changes 3.
• The rate of congenital syphilis can be reduced by universal syphilis screening in pregnancy, repeat testing for high-risk women, and treatment of infected women with benzathine penicillin G 5.
• Updating guidance on syphilis testing and treatment in pregnancy to reflect global norms could prevent congenital syphilis and save newborn lives 5.