This is a successful experience report carried out in a medium-complexity hospital providing 100% SUS care and serving as a referral center in the interior of the state of São Paulo. Although about 10% of the population reports a penicillin allergy, scientific evidence shows that fewer than 1% have a true IgE-mediated allergic reaction. Many reported reactions are misdiagnosed or do not correspond to true allergic processes. In pregnancy, penicillin desensitization becomes a key strategy to ensure safe and effective treatment, contributing to the prevention of complications and to improved maternal–infant health outcomes.

To qualify the hospital to become a referral center for “Penicillin Desensitization in Pregnant Women,” increasing adherence by enabling the procedure closer to patients’ homes, ensuring greater effectiveness, reducing unnecessary use of alternative antibiotics, and decreasing future NICU admissions of newborns whose mothers would otherwise be considered inadequately treated.

The program was implemented through creation of a standardized protocol with all guidance required for effectiveness. The involved teams were trained, educational materials were distributed to regional units, and an admission flow was established so the procedure could occur within critical care units, with full monitoring in cases of potential anaphylaxis.

In the evaluated period (2024), penicillin desensitization was performed for all referred patients in the region; five patients received medications in the intensive care unit, with successful completion enabling effective treatment of syphilis and preventing fetal transmission. Penicillin desensitization is crucial, as appropriate treatment of congenital syphilis prevents serious consequences for mother and baby. Penicillin is among the safest antibiotics in pregnancy, minimizing risks and severe complications such as preterm birth and low birth weight.

The adoption of a penicillin desensitization protocol for pregnant women is strategic in obstetrics and maternal–child health. It allows pregnant patients with a history of allergy to receive the safest and most effective treatment for infections such as congenital syphilis, preventing serious complications and expanding access by bringing care closer to where patients live.