c7 Cefaclor

Allergens within Drugs

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Allergen Description

Cefaclor is a semisynthetic β-lactam antibiotic drug belonging to the cephalosporin subgroup. Like all β-lactams, cefaclor readily reacts with tissue proteins in vivo, thereby sensitizing susceptible individuals. The allergenic determinants (epitopes) of cephalosporins such as cefaclor are not fully known. This is a consequence of the unstable structures which are formed upon reaction with lysine amino groups in proteins. The primary unstable conjugates are rapidly degraded and transformed into structures where the six-membered dihydrothiazine ring is absent (1-2).
 

Allergen Exposure

Cefaclor is an antibiotic for oral use and exposure to the allergen occurs by gastrointestinal absorption. Exposure can also occur upon inhalation, especially as an occupational hazard during manufacturing.

Potential Cross-Reactivity

Cross-reactivity may exist between cephalosporins with similar C-7 side-chains and between cephalosporins and penicillins with identical side-chains (3). In practise, this means cefaclor may cross-react with cephalosporins such as cephalexin, cephaloglycin, and cefatrizine and semi-synthetic penicillins such as ampicillin and amoxicillin. These potentially cross-reactive β-lactams should therefore be used with caution in a cefaclor-allergic patient.

Clinical Experience

Immediate reactions (maximum 1 hour after drug intake) have the highest probability of being IgE-mediated. Clinical pictures typical for immediate reactions to β-lactams are urticaria, with or without angioedema, and anaphylaxis. Anaphylactic reactions to cefaclor have been reported since the 80’s (4). Hama and Mori reported 1988 a high incidence of anaphylactic reactions to cefaclor (5). Other kinds of hypersensitivity reactions (non IgE-mediated) to cefaclor include “serum-sickness” and erythema multiforma (6).
 
IgE antibodies to cefaclor have been detected in vitro in some recent studies by Korean and Spanish teams. Thus, Kim and co-workers described 4 cases of anaphylaxis caused by cefaclor in which a specific IgE response to cefaclor was demonstrated using an ELISA (7). In Spain, Torres and her team evaluated the in vitro IgE response to cefaclor in 7 patients who had experienced anaphylaxis or urticaria (8).

Compiled by Dr Lennart Venemalm, Phadia

References:

    1. Venemalm, L. Pyrazinone Conjugates as Potential Cephalosporin Allergens. Bioorg Med Chem Lett 2001; 11: 1869-70.
    2. Perez-Inestrosa, E., Suau, R., Montanez, M.I., Rodriguez, R., Mayorga, C., Torres, M.J., Blanca, M. Cephalosporin chemical reactivity and its immunological implications. Curr Opin Allergy Clin Immunol 2005; 5: 323-30.
    3. Antunez, C., Blanca-Lopez, N., Torres, M.J., Mayorga, C., Perez-Inestrosa, E., Montanez, M.I., Fernandez, T., Blanca, M. Immediate allergic reactions to cephalosporins: Evaluation of cross-reactivity with a panel of penicillins and cephalosporins. J Allergy Clin Immunol 2006; 117: 404-10.
    4. Nishioka, K., Katayama, I., Kobayashi, Y., Takijiri, C. Anaphylaxis due to cefaclor hypersensitivity. J Dermatol 1986; 13 (3): 226-27.
    5. Hama, R., Mori, K. High incidence of anaphylactic reactions to cefaclor. Lancet 1988  Jun 11; 1: 1331.
    6. Joubert, G.I., Hadad, K., Matsui, D., Gloor, J., Rieder, M.J. Selection of treatment of cefaclor-associated urticarial, serum sickness-like reactions and erythema multiforme by emergency pediatricians: lack of a uniform standard of care. Can J Clin Pharmacol 1999; 6(4): 197-01.
    7. Kim, S.H., Choi, J.H., Park, H.S. Heterogeneity of the IgE response to allergenic determinants of cefaclor in serum samples from patients with cefaclor-inuced anaphylaxis. Ann Allergy Asthma Immunol 2005; 94(6): 700-04.
    8. Antunez, C., Blanca-Lopez, N., Torres, M.J., Mayorga, C., Perez-Inestrosa, E., Montanez, M.I., Fernandez, T., Blanca, M. Immediate allergic reactions to cephalosporins: Evaluation of cross-reactivity with a panel of penicillins and cephalosporins. J Allergy Clin Immunol 2006; 117(2): 404-10.

2007



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