Selective immediate hypersensitivity to ceftriaxone

Abstract

C eftriaxone is a third-generation cephalosporin used for serious infections. There have been very few reports of type I allergies ( 1), even though the frequency of hypersensitivity reactions to ceftriaxone is 3% ( 2). We studied a 68-year-old man who had developed urticaria, dyspnea, shortness of breath, dizziness, tachycardia, and severe hypotensionwithin 15 min after intramuscularadministration of the first gram of ceftriaxone as prophylaxis for a cataract operation. After treatment with subcutaneous epinephrine, 6-methyl-prednisolone, and chlorphenamine intravenously, symptoms resolved completely in 12 h. Ten months later, we skin-tested the patient with penicilloylpolylysine (Allergopen, Reinbek, Germany), minor determinant mixture (Allergopen), benzylpenicillin, ampicillin, and amoxicillin, as well as ceftriaxone, cefuroxime, cephalothin, ceftazidime, cefotaxime, and cefamandole, as previously described ( 1). All cephalosporins were used at a concentration of 2 mg/ml in 0.9% NaCl. The patient responded positively to prick testing with ceftriaxone (wheal 7×8 mm). Prick and intradermal histamine tests produced wheals with maximum diameters of 8 and 12 mm, respectively. Intradermal tests with the above cephalosporins were negative in 40 healthy control subjects, 10 of whom had previously tolerated ceftriaxone. Assays (UniCAP® specific IgE; Pharmacia & Upjohn, Uppsala, Sweden) for specific IgE to penicilloyl G, penicilloyl V, ampicilloyl, amoxicilloyl, ceftriaxone, cefuroxime, cefaclor, cephalexin, cefotaxime, and cefatrizine were negative (<0.35 kU/l). All the cephalosporin assays except cefaclor were experimental prototypes. Single-blind, placebo-controlled oral challenges with penicillin V (1000 000 IU), ampicillin (1 g), cephalexin (500 mg), cefaclor (500 mg), and cefixime (400 mg) were also performed (each on a different day). Increasing amounts (0.01, 0.1, and 1.0) of the therapeutic doses, indicated in parentheses, were administered at 1-h intervals. No reactions were observed to the challenges. Our clinical findings and the positive prick test with ceftriaxone suggest that the patient developed type-I hypersensitivity. We could not show specific IgE by RAST. It should be considered that we used experimental prototypes, and that cephalosporin allergenic determinants have not been fully identified ( 3). Furthermore, in our case, the assays were performed 10 months after anaphylactic shock and it is possible that the IgE titer had meanwhile fallen below the cutoff value, as observed with penicilloyl IgE antibodies ( 4). We had previously diagnosed a case of immediate hypersensitivity to ceftriaxone ( 1). This subject showed skin-test and RAST positivity to both ceftriaxone and cefotaxime, which have identical (2-amino-4-thiazolyl) (methoxyimino) acetyl side-chains; thus, his reaction was probably caused by selective sensitization to side-chain determinants, as confirmed by skin tests and in vitro assays, as well as negative challenge results with other β-lactams. The present subject displayed skin-test and RAST negativity to cefotaxime as well as to the other drugs and tolerated challenges with other β-lactams. Thus, the patient's reactivity could have been to the entire ceftriaxone molecule ( Fig. 1), as previously demonstrated with cefaclor ( 3). Chemical structure of ceftriaxone. To our knowledge, this is the first case in which selective immediate hypersensitivity to ceftriaxone has been demonstrated. There are too few studies on selective hypersensitivity to single cephalosporins to allow the routine prescription of an alternative cephalosporin. In any case, such prescription should be given only after a careful allergologic examination including the relevant challenge.