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Keywords:

  • ceftazidime;
  • immediate hypersensitivity;
  • skin tests

Ceftazidime is a third-generation cephalosporin with a frequency of hypersensitivity reactions (mostly rashes) of about 0.5% (1) and very few reports of causing IgE-mediated reactions (2).

We studied a 16-year-old girl who suffered from allergic oculorhinitis (grasses and olive tree) and had experienced anaphylactic shock (urticaria, rhinitis, wheezing,dyspnea, and hypotension)within 10 min after intravenous administration of the first dose (1 g) of ceftazidime for bronchopneumonia. Her symptoms subsided 6 h after subcutaneous epinephrine, betamethasone (8 mg intravenous), and chlorphenamine (10 mg intravenous).

Ten months earlier, she had tolerated intramuscular ceftazidime.

Two years later, the patient underwent skin tests with penicilloylpolylysine (Allergopen, Reinbek, Germany), minor determinant mixture (Allergopen), benzylpenicillin, ampicillin, and amoxicillin, as well as ceftazidime, cefotaxime, ceftriaxone, cefuroxime, cefamandole, cephalothin, cephalexin, cefaclor, and cefixime, as previously described (3). Cephalosporins were used at a concentration of 2 mg/ml in 0.9% NaCl. Intradermal testing with ceftazidime produced a wheal of 6×8 mm. Prick and intradermal histamine tests produced wheals with maximum diameters of 7 and 10 mm, respectively. Intradermal tests with the above cephalosporins were negative in 40 control subjects, seven of whom had previously tolerated ceftazidime.

Assays (UniCAP® specific IgE; Pharmacia & Upjohn, Uppsala, Sweden) for specific IgE to penicilloyl G, penicilloyl V, ampicilloyl, amoxicilloyl, cefaclor, and ceftazidime were negative (<0.35 kU/l). The ceftazidime assay was an experimental prototype.

We performed single-blind, placebo-controlled oral challenges with penicillin V (therapeutic dose: 1 000 000 IU), ampicillin (1 g), cephalexin (500 mg), cefaclor (500 mg), cefuroxime axetil (500 mg), and cefixime (400 mg) on different days. Increasing amounts (0.01, 0.1, and 1.0) of the therapeutic doses, indicated in parentheses, were administered at 1-h intervals, with negative results.

Clinical findings and the positive intradermal test with ceftazidime suggested a type-I allergic reaction.

The fact that we used an experimental prototype and that we performed our assays 2 years after the reaction may explain the RAST negativity. In the meantime, the IgE titer may have fallen below the cutoff value, as noted with penicilloyl IgE antibodies (4).

We previously diagnosed two cases of immediate hypersensitivity to ceftazidime on the basis of skin-test and RAST positivity (2). One patient – who displayed positive results only to ceftazidime – was not challenged with other β-lactams. The other had reacted to ceftazidime and ceftriaxone in separate episodes and showed skin-test and RAST positivity to both cephalosporins.

The present subject displayed skin-test, RAST, and challenge negativity with other β-lactams (including first-, second-, and third-generation cephalosporins). Thus, the patient's sensitization appeared to involve the entire ceftazidime molecule, as previously demonstrated with cefaclor (5). To our knowledge, this is the first case in which selective immediate hypersensitivity to ceftazidime has been demonstrated.

For evaluating immediate reactions to cephalosporins, it is crucial to test the responsible drug in addition to penicillin determinants.

In assessing the selectivity of the response, negative results in skin testing with cephalosporins other than the culprit one appear to be a reliable indicator of tolerability. However, the routine prescription of alternative cephalosporins on the basis of skin-test negativity should be made the subject of further studies. Meanwhile, such prescriptions should be given only in selected cases after a careful allergologic examination including the relevant challenge.

References

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  2. References
  • 1
    Recchia G, Soncini R. Tolerance of ceftazidime: the Italian experience. G Ital Chemioter 1985;32:393397.
  • 2
    Romano A, Quaratino D, Aimone-Gastin I, et al. Cephalosporin allergy: characterization of unique and cross-reacting cephalosporin antigens. Int J Immunopathol Pharmacol 1997;10 Suppl 2:187191.
  • 3
    Romano A, Quaratino D, Venemalm L, et al. A case of IgE-mediated hypersensitivity to ceftriaxone. J Allergy Clin Immunol 1999;104:11131114.
  • 4
    Adkinson Nf Jr. Risk factors for drug allergy. J Allergy Clin Immunol 1984;74:567572.
  • 5
    Baldo BA. Penicillins and cephalosporins as allergens – structural aspects of recognition and cross-reactions. Clin Exp Allergy 1999;29:744749.DOI: 10.1046/j.1365-2222.1999.00575.x