Anaphylaxis due to ceftriaxone

Background: Ceftriaxone, a third-generation cephalosporin, is widely prescribed for severe infections. Although generally considered safe, it may cause immediate hypersensitivity reac-tions (HSR), including anaphylaxis, representing a significant clinical concern. Objective: To describe a case series of ceftriaxone-induced hypersensitivity reactions, highlighting clinical presentation, management patterns, and implications for rational antibiotic use. Methods: We retrospectively analyzed eight patients evaluated in our allergy department between 2023 and 2025 for immediate HSR to ceftriaxone. Demographic characteristics, clinical manifestations, reaction severity according to Brown’s classification, management, prior exposure, and skin test results were recorded. All patients underwent skin prick testing, which if negative, was followed by intradermal testing. Results: Patients (aged 10–44 years; with five females) presented reactions ranging from urticaria to grade III anaphylaxis. Most reactions occurred outside hospital settings, increasing the risk of delayed recognition and treatment. Despite several reactions fulfilling criteria for anaphylaxis, intramuscular epinephrine was not administered systematically, with management frequently limited to antihistamines and corticosteroids. Four patients reacted after the first reported dose; previous exposure was documented or suspected in most cases. Skin testing supported an immunoglobulin E-mediated mechanism in the majority of patients, and one patient developed anaphylaxis during intradermal testing. A progressive increase in patients was observed over the study period (1 patient in 2023, 2 in 2024, and 5 patients in 2025). One patient successfully completed treatment through a standardized 12-step desensitization protocol. Conclusions: Ceftriaxone-induced HSR could be severe and occur frequently outside controlled medical settings. Under-recognition of anaphylaxis and underuse of epinephrine remain significant concerns. Rational antibiotic prescribing, improved adherence to anaphylaxis management guidelines, and structured allergy evaluation—including desensitization if necessary—are essential to optimize patient safety.