What is the protocol for penicillin desensitization in a pregnant woman with a history of penicillin allergy?

Penicillin Desensitization Protocol for Pregnant Women with Syphilis

Pregnant women with syphilis and penicillin allergy must undergo desensitization followed by penicillin treatment, as there are no proven alternatives that reliably cure fetal infection. 1, 2, 3

Why Desensitization is Mandatory

• Penicillin is the only antibiotic proven to prevent maternal-to-fetal transmission and treat established fetal syphilis infection. 1, 2, 3
• Tetracyclines and doxycycline are absolutely contraindicated in pregnancy due to maternal hepatotoxicity and fetal tooth/bone staining. 2, 3
• Erythromycin does not reliably cross the placenta to cure fetal infection and should never be used. 1, 2, 3

Pre-Desensitization Evaluation

Perform skin testing to confirm true penicillin allergy before proceeding with desensitization. 1, 4

• Intradermal testing is the most reliable biomarker, predicting 100% of breakthrough reactions during desensitization. 4
• Only 7.69% of pregnant women reporting penicillin allergy have confirmed allergy on testing. 4
• Low-risk patients with negative skin tests and negative serum-specific IgE can undergo direct drug provocation testing instead of full desensitization. 4

Desensitization Protocols

Oral Desensitization Protocol (Most Common)

Administer increasing doses of oral penicillin V over 4-6 hours, then transition to full-dose parenteral penicillin G. 5

• This protocol has been successfully used in pregnant women with confirmed immediate hypersensitivity reactions. 5
• 33% of patients experience mild pruritus or urticaria during the procedure, but interruption is rarely necessary. 5
• No extracutaneous reactions or serious adverse events occurred in the original case series. 5

Intravenous Desensitization Protocol (Alternative)

Administer graduated intravenous doses of penicillin over 4 hours in a critical care setting. 6, 7

• This protocol may offer greater safety compared to oral desensitization, though more data are needed. 4
• Requires intensive monitoring with continuous vital signs and immediate access to resuscitation equipment. 6
• Successfully used in pregnant women allergic to both major and minor penicillin determinants. 7

Where to Perform Desensitization

• Conduct desensitization in a critical care unit or intensive care setting with full resuscitation capabilities. 6
• Ensure immediate access to epinephrine, antihistamines, corticosteroids, and airway management equipment. 6
• Have an allergist or immunologist supervise the procedure when possible. 4

Post-Desensitization Treatment

Immediately after successful desensitization, administer the full penicillin treatment regimen appropriate for the stage of syphilis. 5, 7

• For primary, secondary, or early latent syphilis: benzathine penicillin G 2.4 million units IM, followed by a second dose one week later. 2, 3
• For late latent or unknown duration syphilis: benzathine penicillin G 7.2 million units total (three doses of 2.4 million units IM at weekly intervals). 2, 3
• Administer the first dose of benzathine penicillin G in a labor and delivery unit under continuous fetal monitoring for at least 24 hours in viable pregnancies. 8

Monitoring During and After Treatment

• Watch for Jarisch-Herxheimer reaction, which occurs in up to 44% of pregnant women and can cause contractions, fetal heart rate abnormalities, or stillbirth. 8
• Instruct patients to seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment. 3, 8
• Perform pretreatment ultrasound when feasible, particularly after 20 weeks gestation, to assess for fetal involvement. 3, 8
• Check serologic titers monthly until delivery to ensure adequate treatment response. 2, 3

Critical Pitfalls to Avoid

• Never delay treatment due to concerns about Jarisch-Herxheimer reaction or stillbirth risk—untreated syphilis causes far greater fetal harm. 3
• Never substitute erythromycin, tetracyclines, or other non-penicillin antibiotics, as these do not prevent congenital syphilis. 2, 3
• Do not assume all patients reporting penicillin allergy are truly allergic—most are not, and skin testing can safely identify candidates for direct challenge. 4
• Do not discharge a newborn without documented maternal syphilis screening during pregnancy. 2, 3