Cefazolin Hypersensitivity: Toward Optimized Diagnosis.
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.



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.



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.



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.



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.
Department of Immunology, Allergology, Rheumatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Astrid P
AP
Uyttebroek
Department of Immunology, Allergology, Rheumatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium; Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Ine I
II
Decuyper
Department of Immunology, Allergology, Rheumatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Chris H
CH
Bridts
Allergy Unit, Complesso Integrato Columbus, Rome, Italy; Department of Allergology, IRCCS Oasi Maria S.S., Troina, Italy.
Antonino
A
Romano
Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Margo M
MM
Hagendorens
Department of Immunology, Allergology, Rheumatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium. Electronic address: immuno@uantwerpen.be.
Didier G
DG
Ebo
Department of Immunology, Allergology, Rheumatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Vito
V
Sabato
D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002437:Cefazolin / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D012882:Skin Tests
D000900:Anti-Bacterial Agents; D007073:Immunoglobulin E; D002437:Cefazolin
Cefazolin hypersensitivity; Cross-reactivity; Perioperative anaphylaxis; Skin testing