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).
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.
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.
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
- Venemalm, L. Pyrazinone Conjugates as Potential Cephalosporin Allergens. Bioorg Med Chem Lett 2001; 11: 1869-70.
- 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.
- 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.
- Nishioka, K., Katayama, I., Kobayashi, Y., Takijiri, C. Anaphylaxis due to cefaclor hypersensitivity. J Dermatol 1986; 13 (3): 226-27.
- Hama, R., Mori, K. High incidence of anaphylactic reactions to cefaclor. Lancet 1988 Jun 11; 1: 1331.
- 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.
- 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.
- 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.