Treatment of Primary Syphilis in Pregnancy When Benzathine Penicillin G Does Not Achieve the Target RPR Response
Primary syphilis in pregnancy demands prompt serological cure to protect the fetus. When the first-line regimen does not produce the expected response — or when allergy prevents its use — a structured next-line approach is required.
Clinical Scenario: Pregnancy
All pregnant women and people should have serological screening for syphilis as part of their first antenatal assessment. When primary syphilis is identified in pregnancy, achieving serological clearance before delivery is the central clinical priority.
When First-Line Treatment Falls Short
The standard first-line regimen is benzathine penicillin G. This protocol applies when that treatment has not reached the defined goal — a four-fold drop in the quantitative RPR (non-treponemal) titre after treatment — or when penicillin cannot be used due to allergy.
Note: achieving a four-fold RPR titre drop may take several months, and in many pregnancies delivery will occur before this endpoint is reached.
Next-Line Approach
References
- All pregnant women and people should have serological screening for syphilis as part of their first antenatal assessment.
- It may take several months to observe a 4-fold drop in RPR titre and in many pregnancies delivery will occur beforehand.
- The non-penicillin alternative is ceftriaxone, for which limited data are available.
- If a patient is allergic to penicillin but not ceftriaxone, ceftriaxone can be used or penicillin desensitisation and immediate penicillin treatment can be considered.
- In the case of soya or peanut allergy, refer for allergy testing or treat with procaine penicillin or ceftriaxone.