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The Cross-Reactivity and Immunology of β-Lactam Antibiotics

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  • Drug Safety Concepts
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Summary

Allergic reactions to β-lactam antibiotics are well described; however, only the immunochemistry of penicillin has been characterised. Although the major determinant of benzylpenicillin (penicillin G) is commercially licensed for diagnostic applications, minor determinants are only available at some centres to be used for identification of hypersensitive individuals. Cephalosporins share a common bicyclic nuclear structure with penicillin and most cross-reactivity is generated to the β-lactam ring. It is not possible to determine the actual incidence of cross-reactivity between penicillins and cephalosporins, but evidence suggests the true rate is lower than usually appreciated. In vitro testing demonstrates extensive cross-reactivity between penicillin and the carbapenems. Although the rate of clinical cross-reactivity is not known, imipenem should not be given to patients with proven penicillin hypersensitivity. In contrast, aztreonam and the monobactams can be safely given to penicillin-allergic patients.

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References

  • Adkinson NF, Thompson WL, Maddrey WC, Lichtenstein LM. Routine use of penicillin skin testing on an inpatient service. New England Journal of Medicine 285: 22–24, 1971

    Article  PubMed  Google Scholar 

  • Adkinson Jr NF. Risk factors for drug allergy. Journal of Allergy and Clinical Immunology 74: 567–572, 1984

    Article  PubMed  Google Scholar 

  • Adkinson NF, Swabb EA, Sugerman HA. Immunology of the monobactam aztreonam. Antimicrobial Agents and Chemotherapy 25: 93–97, 1984

    Article  PubMed  CAS  Google Scholar 

  • AdkinsonJr NF, Saxon A, Spence MR, Swabb EA. Cross-allergenicity and immunogenicity of aztreonam. Review of Infectious Diseases 7 (Suppl.): S613–S621, 1985

    Article  CAS  Google Scholar 

  • Ahlstedt S, Kristofferson A. Immune mechanisms for induction of penicillin allergy. Progress in Allergy 30: 67–134, 1982

    PubMed  CAS  Google Scholar 

  • Assem ESK, Vickers MR. Tests for penicillin allergy in man. II: The immunological cross-reactivity between penicillin and cephalosporins. Immunology 27: 255–269, 1974

    PubMed  CAS  Google Scholar 

  • Carini C, Margolick J, Yodio J, Ishizaka K. Formation of IgE-binding factor by T-cells of a patient infected with human immunodeficiency virus type I. Proceedings of the National Academy of Sciences of the United States of America 85: 9214–9218, 1988

    Article  PubMed  CAS  Google Scholar 

  • Green GR, Rosenblum AH, Sweet LC. Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin-G. Journal of Allergy and Clinical Immunology 60: 339–345, 1977

    Article  PubMed  CAS  Google Scholar 

  • Idsoe O, Guthe T, Wilcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bulletin of the World Health Organization 38: 159–188, 1968

    PubMed  CAS  Google Scholar 

  • Iwata M, Tokiwa H, Matuhasi T. Detection and characterization of polymers in cephalothin by passive cutaneous anaphylaxis in mice. Archives of Allergy and Applied Immunology 70: 132–137, 1983

    Article  CAS  Google Scholar 

  • Levenson DE, Arndt KA, Stern RS, Van ArsdelJr PP. Immunology and Allergy Clinics of North America 11: 475–491,493-507,1991

    Google Scholar 

  • Levine BB. Immunochemical mechanisms of penicillin allergy. A haptenic model system for the study of allergic diseases on man. New England Journal of Medicine 275: 1115–1125, 1966

    Article  PubMed  CAS  Google Scholar 

  • Levine BB, Redmond AP, Fellner MJ, Voss HE, Levytska V. Penicillin allergy and the heterogeneous immune responses of man to benzylpenicillin. Journal of Clinical Investigation 45: 1895–1906, 1966

    Article  PubMed  CAS  Google Scholar 

  • Levine BB. Antigenicity and cross-reactivity of penicillin and cephalosporins. Journal of Infectious Diseases 128 (Suppl.): S364–S366, 1973

    Article  PubMed  Google Scholar 

  • Levine BB, Redmond AP. The nature of the antigen-antibody complex initiating the specific wheal-and-flare reaction in sensitized skin. Journal of Clinical Investigation 47: 556–567, 1968

    Article  PubMed  CAS  Google Scholar 

  • Lin RY. A perspective on penicillin allergy. Archives of Internal Medicine 152: 930–937, 1992

    Article  PubMed  CAS  Google Scholar 

  • Lucey DR, Zajac RA, Melcher GP, Butzin CA, Boswell RN. Serum IgE levels in 622 persons with human immunodeficiency virus infection: IgE elevation with marked depletion of CD4+ T-cells. AIDS Research and Human Retroviruses 6: 427–429, 1990

    Article  PubMed  CAS  Google Scholar 

  • Naclerio R, Mizrahi EA, Adkinson Jr NF. Immunological observations during desensitization and maintenance of clinical tolerance to penicillin. Journal of Allergy and Clinical Immunology 79: 523–532, 1987

    Article  Google Scholar 

  • Pedersen-Bjergaard J. Cephalothin in the treatment of penicillin sensitive patients. Acta Allergolica XXII: 299–306, 1967

    Google Scholar 

  • Petz LD. Immunologic reactions of humans to cephalosporins. Postgraduate Medical Journal 47 (Suppl.): 64–69, 1971

    PubMed  Google Scholar 

  • Petz LD. Immunoreactivity between penicillin and cephalosporins: a review. Journal of Infectious Diseases 137 (Suppl.): S74–S79, 1978

    Article  PubMed  Google Scholar 

  • Redelmeier DA, Sox HC. The role of skin testing for penicillin allergy. Archives of Internal Medicine 150: 1939–1946, 1990

    Article  PubMed  CAS  Google Scholar 

  • Saxon A, Adelman DA, Patel A, Hadju R, Calandra GB, et al. Imipenem cross reactivity with penicillin in humans. Journal of Allergy and Clinical Immunology 82: 213–217, 1988

    Article  PubMed  CAS  Google Scholar 

  • Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Annals of Internal Medicine 107: 204–215, 1987

    PubMed  CAS  Google Scholar 

  • Shearer GM, Schmitt-Verhulst AM, Pettinelli CB, Miller MW, Gilheany PE. H-2 linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate. Journal of Experimental Medicine 149: 1407–1423, 1979

    Article  PubMed  CAS  Google Scholar 

  • Shibata K, Atsumi T, Horiuchi Y, Mashimo K. Immunological crossreactivity of cephalothin and its related compounds with benzylpenicillin (penicillin-G). Nature 212: 419–420, 1966

    Article  PubMed  CAS  Google Scholar 

  • Siegel BB, Levine BB. Antigenic specificities of skin sensitizing antibodies in the sera from patients with immediate septemic allergic reactions of penicillin. Journal of Allergy 35: 488–498, 1964

    Article  PubMed  CAS  Google Scholar 

  • Smith JW, Johnson JE, Cluff LE. Studies on the epidemiology of adverse drug reactions. II. An evaluation of penicillin allergy. New England Journal of Medicine 274: 998–1002, 1966

    Article  PubMed  CAS  Google Scholar 

  • Solley GO, Gleich GJ, Van Dellen RG. Penicillin allergy: clinical experience with a battery of skin-test reagents. Journal of Allergy and Clinical Immunology 69: 238–244, 1982

    Article  PubMed  CAS  Google Scholar 

  • Stember RH, Levine BB. Prevalence of allergic diseases, penicillin hypersensitivity and aeroallergen hypersensitivity in various populations. Journal of Allergy and Clinical Immunology 51: 100, 1973

    Article  Google Scholar 

  • Sullivan TJ. Drug allergy. In Middleton et al (Eds) Allergy principles and practice, 4th ed., pp. 1726–1746, CV Mosby, St. Louis, 1993

    Google Scholar 

  • Sullivan TJ, Ong RC, Gilliam LK. Studies of the multiple drug allergy syndrome. Abstract. Journal of Allergy and Clinical Immunology 83: 270, 1989

    Article  Google Scholar 

  • Sullivan TJ, Wedner HJ, Shatz GS, Yecies LD, Parker CW Skin testing to detect penicillin allergies. Journal of Allergy and Clinical Immunology 68: 171–180, 1981

    Article  PubMed  CAS  Google Scholar 

  • Sullivan TJ, Yecies LD, Shatz GS. Desensitization of patients allergic to penicillin using orally administered beta-lactam antibiotics. Journal of Allergy and Clinical Immunology 69: 275–282, 1982

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi M, Hayakawa K, Tada T. Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for I region gene product. Journal of Immunology 116: 542–548, 1976

    CAS  Google Scholar 

  • Terr AI. Mechanisms of hypersensitivity. In Stites & Terr (Eds) Basic and clinical immunology, 7th ed., p. 376, Appleton & Lange, East Norwalk, 1991

    Google Scholar 

  • Warrington RJ, Simons FE, Ho HW, Gorski BA. Diagnosis of penicillin allergy by skin testing: the Manitou experience. Canadian Medical Association Journal 118:787–791, 1978

    PubMed  CAS  Google Scholar 

  • Weiss ME, Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clinical Allergy 18: 515–540, 1988

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Allergy and Immunology, University of California, San Francisco, 533 Parnassus, U-426, San Francisco, California, 94143-0724, USA

    Jeffrey L. Kishiyama &  Daniel C. Adelman

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  1. Jeffrey L. Kishiyama
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  2. Daniel C. Adelman
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Kishiyama, J.L., Adelman, D.C. The Cross-Reactivity and Immunology of β-Lactam Antibiotics. Drug-Safety 10, 318–327 (1994). https://doi.org/10.2165/00002018-199410040-00006

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