Treatment of syphilis in pregnancy

Stage of syphilis	Treatment
Primary/secondary/early latent	Penicillin G benzathine (Bicillin L-A) 2.4 million units IM in a single dose (usually administered as 1.2 million units in each buttock)*
Late latent/tertiary/unknown duration	Penicillin G benzathine (Bicillin L-A) 2.4 million units IM once weekly (usually administered as 1.2 million units in each buttock) for 3 weeks (7.2 million units total dose)^¶
Neurosyphilis (including ocular syphilis)^Δ	Aqueous crystalline penicillin G (intravenous) 18 to 24 million units per day, administered as 3 to 4 million units IV every 4 hours or as a continuous infusion over 24 hours for 10 to 14 days
	OR
	Penicillin G procaine 2.4 million units IM once daily (usually administered as 1.2 million units in each buttock) plus probenecid 500 mg PO 4 times daily, both for 10 to 14 days
Post-exposure prophylaxis	Penicillin G benzathine (Bicillin L-A) 2.4 million units IM in a single dose (usually administered as 1.2 million units in each buttock)

Pregnant women are treated with the penicillin regimen appropriate for their stage of infection. Parenteral (IM or IV) penicillin G is the only therapy with documented safety and efficacy for both mother and fetus during pregnancy. Pregnant women with a history of penicillin allergy should be desensitized and treated with penicillin. Refer to the relevant topic review for further guidance on management of pregnant patients with penicillin allergy.
If penicillin desensitization is not possible for treatment of early syphilis (primary, secondary, or latent <2 years), the World Health Organization (WHO) suggests using, with caution, erythromycin 500 mg 4 times daily for 14 days, ceftriaxone 1 g IM once daily for 10 to 14 days, or azithromycin 2 g once orally (when local susceptibility to azithromycin is likely). If penicillin desensitization is not possible for treatment of late syphilis, the WHO recommends treatment with erythromycin 500 mg orally 4 times daily for 30 days. Macrolides (eg, erythromycin) do not completely cross the placental barrier; therefore, the WHO also recommends that infants born to women treated with non-penicillin regimens receive a 10 to 15 day course of parenteral penicillin treatment.

IM: intramuscular; IV: intravenous; PO: oral.
* If serologic failure is detected at follow-up and additional follow-up cannot be assured, consider retreating with penicillin G benzathine 2.4 million units IM once weekly for 3 weeks. Prompt cerebrospinal fluid examination is recommended.
¶ If a dose is missed for more than 14 days, then the full 3 dose course of therapy should be restarted.
Δ Penicillin G benzathine 2.4 million units IM once per week for up to 3 weeks may be administered after completion of IV penicillin G treatment to provide a comparable total duration of therapy as latent syphilis.

Data from:

Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
World Health Organization guidelines for treatment of Treponema pallidum (syphilis), 2016. http://apps.who.int/iris/bitstream/10665/249572/1/9789241549806-eng.pdf?ua=1 (Accessed on August 15, 2018).

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Treatment of syphilis in pregnancy