Cefazolin Hypersensitivity: Toward Optimized Diagnosis

Background Correct diagnosis of cefazolin hypersensitivity is not straightforward, mainly because of the absence of in vitro tests and uncertainties concerning the optimal cefazolin concentration for skin testing. Cross-reactivity studies suggest cefazolin hypersensitivity to be a selective hypersensitivity. Objective The first objective was to confirm that the application of a higher than 2 mg/mL test concentration could increase skin test sensitivity. A second part aimed at investigating the cross-reactivity between cefazolin and other β-lactam antibiotics. Methods A total of 66 patients referred to our clinic after experiencing perioperative anaphylaxis, and exposed to cefazolin, underwent skin testing with cefazolin up to 20 mg/mL. Patients exhibiting a positive skin test with cefazolin had a panel of skin tests with other β-lactams and, if indicated, graded drug challenges to study cross-reactivity. Results Increasing skin test concentration from the recommended 2 mg/mL to 20 mg/mL identified an additional 7 of 19 (27%) patients, who would otherwise have displayed negative skin testing. The concentration was proven nonirritating in 30 cefazolin-exposed control individuals in whom an alternative culprit for perioperative anaphylaxis was identified. Graded challenge testing, after negative skin testing, displayed that all patients tolerated alternative β-lactam antibiotics (ie, amoxicillin, cephalosporins, monobactams, and carbapenems). Of them, 11 individuals also tolerated an alternative cephalosporin, suggesting that cefazolin hypersensitivity (generally) is a selective allergy. Conclusions Increasing cefazolin concentration for skin tests up to 20 mg/mL benefits the sensitivity of diagnosis. Furthermore, our data confirm that cefazolin hypersensitivity seems to be a selective allergy with good tolerance to other β-lactam antibiotics.