Background: Cephalosporin administration in patients with a history of penicillin allergy is controversial. Studies looking at the safety of cephalosporin in patients with a history of penicillin allergy lacked a control group, had a small number of patients, and/or lacked confirmation of penicillin allergy by penicillin skin testing. The purpose of this study was to determine whether patients with penicillin allergy were at increased risk of adverse drug reactions when administered cephalosporin. Methods: A cohort study of patients with a history of penicillin allergy and a positive or negative penicillin skin test when administered cephalosporin was conducted. Charts were reviewed for adverse drug reactions to cephalosporin after penicillin skin testing. Results: Eighty-five patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin. Five (6%) of 85 cases had an adverse drug reaction to cephalosporin as compared to 5 (0.7%) of 726 of the referent population (p = 0.0019). The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2 (2%) of 85 compared to 1 (0.1%) of 726 amongst the referent population (p = 0.0304). Conclusion: A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. We recommend penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.

1.
Anne S, Reisman RE: Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol 1995;74:167–170.
2.
Executive summary of disease management of drug hypersensitivity: a practice parameter. Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1999;83:665–700.
3.
Blanca M, Fernandez J, Miranda A, Terrados S, Torres MJ, Vega JM, Avila MJ, Perez E, Garcia JJ, Suau R: Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies. J Allergy Clin Immunol 1989;83:381–385.
4.
Antunez C, Blanca-Lopez N, Torres MJ, Mayorga C, Perez-Inestrosa E, Montanez MI, 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;117:404–410.
5.
Miranda A, Blanca M, Vega JM, Moreno F, Carmona MJ, Garcia JJ, Segurado E, Justicia JL, Juarez C: Cross-reactivity between a penicillin and a cephalosporin with the same side chain. J Allergy Clin Immunol 1996;98:671–677.
6.
Assem ES, Vickers MR: Tests for penicillin allergy in man. II. The immunological cross-reaction between penicillins and cephalosporins. Immunology 1974;27:255–269.
7.
Girard JP: Common antigenic determinants of penicillin G, ampicillin and the cephalosporins demonstrated in men. Int Arch Allergy Appl Immunol 1968;33:428–438.
8.
Saxon A, Beall GN, Rohr AS, Adelman DC: Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987;107:204–215.
9.
Solley GO, Gleich GJ, Van Dellen RG: Penicillin allergy: clinical experience with a battery of skin-test reagents. J Allergy Clin Immunol 1982;69:238–244.
10.
Thoburn R, Johnson JE 3rd, Cluff LE: Studies on the epidemiology of adverse drug reactions. IV. The relationship of cephalothin and penicillin allergy. JAMA 1966;198:345–348.
11.
Kelkar PS, Li JT: Cephalosporin allergy. N Engl J Med 2001;345:804–809.
12.
Apter AJ, Kinman JL, Bilker WB, Herlim M, Margolis DJ, Lautenbach E, Hennessy S, Strom BL: Is there cross-reactivity between penicillins and cephalosporins? Am J Med 2006;119:354.e11–354.e19.
13.
Pichichero ME, Casey JR: Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis. Otolaryngol Head Neck Surg 2007;136:340–347.
14.
Romano A, Gueant-Rodriguez RM, Viola M, Pettinato R, Gueant JL: Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004;141:16–22.
15.
American Academy of Pediatrics, Subcommittee on Management of Sinusitis and Committee on Quality Improvement: Clinical practice guideline: management of sinusitis. Pediatrics 2001;108:798–808.
16.
Pumphrey RS: Fatal anaphylaxis in the UK, 1992–2001. Novartis Found Symp 2004;257:116–128; discussion 128–132, 157–160, 276–285.
17.
Novalbos A, Sastre J, Cuesta J, De Las Heras M, Lluch-Bernal M, Bombin C, Quirce S: Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins. Clin Exp Allergy 2001;31:438–443.
18.
International drug monitoring: the role of the hospital. World Health Organ Tech Rep Ser 1969;425:5–24.
19.
Audicana M, Bernaola G, Urrutia I, Echechipia S, Gastaminza G, Munoz D, Fernandez E, Fernandez de Corres L: Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin. Allergy 1994;49:108–113.
20.
Shepherd GM, BD: Administration of cephalosporin antibiotics to patients with a history of penicillin allergy. J Allergy Clin Immunol 1993;91:262.
21.
Warrington RJ, Simons FE, Ho HW, Gorski BA: Diagnosis of penicillin allergy by skin testing: the Manitoba experience. Can Med Assoc J 1978;118:787–791.
22.
Macy E, Burchette RJ: Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy 2002;57:1151–1158.
23.
Greenberger PA: 8. Drug allergy. J Allergy Clin Immunol 2006;117:S464–S470.
24.
Atanaskovic-Markovic M, Velickovic TC, Gavrovic-Jankulovic M, Vuckovic O, Nestorovic B: Immediate allergic reactions to cephalosporins and penicillins and their cross-reactivity in children. Pediatr Allergy Immunol 2005;16:341–347.
25.
Blanca M, Romano A, Torres MJ, Fernandez J, Mayorga C, Rodriguez J, Demoly P, Bousquet PJ, Merk HF, Sanz ML, Ott H, Atanaskovic-Markovic M: Update on the evaluation of hypersensitivity reactions to betalactams. Allergy 2009;64:183–193.
26.
Frigas E, Park MA, Narr BJ, Volcheck GW, Danielson DR, Markus PJ, Olson KE, Schroeder DR, Kita H: Preoperative evaluation of patients with history of allergy to penicillin: comparison of 2 models of practice. Mayo Clin Proc 2008;83:651–662.
27.
Li JT, Markus PJ, Osmon DR, Estes L, Gosselin VA, Hanssen AD: Reduction of vancomycin use in orthopedic patients with a history of antibiotic allergy. Mayo Clin Proc 2000;75:902–906.
28.
Park M, Markus P, Matesic D, Li JT: Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy. Ann Allergy Asthma Immunol 2006;97:681–687.
29.
Greenberger PA, K, JC: Utility of penicillin major and minor determinants for identification of allergic reactions to cephalosporins. J Allergy Clin Immunol 2005;115:S182.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.