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The Use of Cephalosporins in Penicillin-allergic Patients: A Literature Review

      Abstract

      Background

      The practice of avoiding cephalosporin administration to penicillin-allergic patients persists despite the low rate of cross reactions between both groups of antibiotics.

      Objective

      The purpose of this literature review is to evaluate the published evidence regarding the commonly held belief that patients with a history of an allergic reaction to penicillin have a significantly increased risk of an allergic reaction to cephalosporins.

      Materials and Methods

      Articles were identified through a computerized search of MEDLINE from 1950 to the present using the search terms “penicillin$,” “cephalosporin$,” “allerg$,” “hypersensitivity,” and “cross-react$.” All articles were reviewed, and additional sources cited in them were added to the literature review.

      Results

      Penicillins have a cross allergy with first-generation cephalosporins (odds ratio 4.8; confidence interval 3.7–6.2) and a negligible cross allergy with second-generation cephalosporins (odds ratio 1.1; confidence interval 0.6–2.1). Laboratory and cohort studies confirm that the R1 side chain is responsible for this cross reactivity. Overall cross reactivity between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cephalosporins that share a similar R1 side chain.

      Conclusions

      Although a myth persists that approximately 10% of patients with a history of penicillin allergy will have an allergic reaction if given a cephalosporin, the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains. However, a single study reported the prevalence of cross reactivity with cefadroxil as high as 27%. For penicillin-allergic patients, the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.

      Keywords

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      References

        • Herbert M.E.
        • Brewster G.S.
        • Lanctot-Herbert M.
        Medical myth: ten percent of patients who are allergic to penicillin will have serious reactions if exposed to cephalosporins.
        West J Med. 2000; 172: 341
        • Pichichero M.E.
        • Casey J.R.
        Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis.
        Otolaryngol Head Neck Surg. 2007; 136: 340-347
        • Thoburn R.
        • Johnson 3rd, J.E.
        • Cluff L.E.
        Studies on the epidemiology of adverse drug reactions. IV. The relationship of cephalothin and penicillin allergy.
        JAMA. 1966; 198: 345-348
        • Petz L.D.
        Immunologic reactions of humans to cephalosporins.
        Postgrad Med J. 1971; 47: 64-69
        • Petz L.D.
        • Fudenberg H.H.
        Coombs-positive hemolytic anemia caused by penicillin administration.
        N Engl J Med. 1966; 274: 171-178
        • Dash C.H.
        Penicillin allergy and the cephalosporins.
        J Antimicrob Chemother. 1975; 1: 107-118
        • Assem E.S.
        • Vickers M.R.
        Tests for penicillin allergy in man. II. The immunological cross-reaction between penicillins and cephalosporins.
        Immunology. 1974; 27: 255-269
        • Batchelor F.R.
        • Dewdney J.M.
        • Weston R.D.
        • Wheeler A.W.
        The immunogenicity of cephalosporin derivatives and their cross-reaction with penicillin.
        Immunology. 1966; 10: 21-33
        • Mine Y.
        • Nishida M.
        • Goto S.
        • Kuwahara S.
        Cefazolin, a new semisynthetic cephalosporin antibiotic. IV. Antigenicity of cefazolin and its cross reactivity with benzylpenicillin, ampicillin and cephaloridine.
        J Antibiot (Tokyo). 1970; 23: 195-203
        • Tsuchiya K.
        • Shiho O.
        • Kondo M.
        Immunological cross-reactivities of sulfocephalosporins.
        J Antibiot (Tokyo). 1979; 32: 488-495
        • Antunez C.
        • Fernandez T.
        • Blanca-Lopez N.
        • et al.
        IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response.
        Allergy. 2006; 61: 940-946
        • Arndt P.A.
        • Garratty G.
        Cross-reactivity of cefotetan and ceftriaxone antibodies, associated with hemolytic anemia, with other: cephalosporins and penicillin.
        Am J Clin Pathol. 2002; 118: 256-262
        • Audicana M.
        • Bernaola G.
        • Urrutia I.
        • et al.
        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
        • Blanca M.
        • Fernandez J.
        • Miranda A.
        • et al.
        Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies.
        J Allergy Clin Immunol. 1989; 83: 381-385
        • Katsutani N.
        • Shionoya H.
        Immunogenicity of various beta-lactam antibiotic-protein conjugates and cross-reactivity of the antibodies produced in guinea pig.
        Int Arch Allergy Immunol. 1993; 100: 128-134
        • Mauri-Hellweg D.
        • Zanni M.
        • Frei E.
        • et al.
        Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.
        J Immunol. 1996; 157: 1071-1079
        • Miranda A.
        • Blanca M.
        • Vega J.M.
        • et al.
        Cross-reactivity between a penicillin and a cephalosporin with the same side chain.
        J Allergy Clin Immunol. 1996; 98: 671-677
        • Romano A.
        • Mayorga C.
        • Torres M.J.
        • et al.
        Immediate allergic reactions to cephalosporins: cross-reactivity and selective responses.
        J Allergy Clin Immunol. 2000; 106: 1177-1183
        • Sastre J.
        • Quijano L.D.
        • Novalbos A.
        • et al.
        Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to amoxicillin and with good tolerance of penicillin.
        Allergy. 1996; 51: 383-386
        • Fonacier L.
        • Hirschberg R.
        • Gerson S.
        Adverse drug reactions to a cephalosporins in hospitalized patients with a history of penicillin allergy.
        Allergy Asthma Proc. 2005; 26: 135-141
        • Romano A.
        • Gueant-Rodriguez R.M.
        • Viola M.
        • Pettinato R.
        • Gueant J.L.
        Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins.
        Ann Intern Med. 2004; 141: 16-22
        • Novalbos A.
        • Sastre J.
        • Cuesta J.
        • et al.
        Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins.
        Clin Exp Allergy. 2001; 31: 438-443
        • Beam Jr., T.R.
        • Spooner J.
        Cross allergenicity between penicillins and cephalosporins.
        Chemioterapia. 1984; 3: 390-393
        • Solensky R.
        • Earl H.S.
        • Gruchalla R.S.
        Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses.
        Arch Intern Med. 2002; 162: 822-826
        • Macy E.
        • Burchette R.J.
        Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.
        Allergy. 2002; 57: 1151-1158
        • Daulat S.
        • Solensky R.
        • Earl H.S.
        • Casey W.
        • Gruchalla R.S.
        Safety of cephalosporin administration to patients with histories of penicillin allergy.
        J Allergy Clin Immunol. 2004; 113: 1220-1222
        • Goodman E.J.
        • Morgan M.J.
        • Johnson P.A.
        • Nichols B.A.
        • Denk N.
        • Gold B.B.
        Cephalosporins can be given to penicillin-allergic patients who do not exhibit an anaphylactic response.
        J Clin Anesth. 2001; 13: 561-564
        • Apter A.J.
        • Kinman J.L.
        • Bilker W.B.
        • et al.
        Is there cross-reactivity between penicillins and cephalosporins?.
        Am J Med. 2006; 119 (e311–20): 354
        • Anne S.
        • Reisman R.E.
        Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy.
        Ann Allergy Asthma Immunol. 1995; 74: 167-170
        • Solensky R.
        • Earl H.S.
        • Gruchalla R.S.
        Clinical approach to penicillin-allergic patients: a survey.
        Ann Allergy Asthma Immunol. 2000; 84: 329-333
        • Kelkar P.S.
        • Li J.T.
        Cephalosporin allergy.
        N Engl J Med. 2001; 345: 804-809
        • Surtees S.J.
        • Stockton M.G.
        • Gietzen T.W.
        Allergy to penicillin: fable or fact?.
        BMJ. 1991; 302: 1051-1052
        • Idsoe O.
        • Guthe T.
        • Willcox R.R.
        • de Weck A.L.
        Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock.
        Bull World Health Organ. 1968; 38: 159-188
        • Girard J.P.
        Common antigenic determinants of penicillin G, ampicillin and the cephalosporins demonstrated in men.
        Int Arch Allergy Appl Immunol. 1968; 33: 428-438
        • Levine B.B.
        • Redmond A.P.
        • Fellner M.J.
        • Voss H.E.
        • Levytska V.
        Penicillin allergy and the heterogenous immune responses of man to benzylpenicillin.
        J Clin Invest. 1966; 45: 1895-1906
        • Anderson J.A.
        Cross-sensitivity to cephalosporins in patients allergic to penicillin.
        Pediatr Infect Dis. 1986; 5: 557-561
        • Levine B.B.
        Antigenicity and cross-reactivity of penicillins and cephalosporins.
        J Infect Dis. 1973; 128: S364-S366
        • Saxon A.
        • Beall G.N.
        • Rohr A.S.
        • Adelman D.C.
        Immediate hypersensitivity reactions to beta-lactam antibiotics.
        Ann Intern Med. 1987; 107: 204-215
        • Abraham E.P.
        Penicillins and cephalosporins.
        Pure Appl Chem. 1971; 28: 399-412
        • Hewitt W.L.
        The cephalosporins—1973.
        J Infect Dis. 1973; 128: S312-S319
        • Newton G.G.
        • Abraham E.P.
        • Kuwabara S.
        Preliminary observations on the formation and breakdown of “cephalosporoic acids”.
        Antimicrob Agents Chemother (Bethesda). 1967; 7: 449-455
        • Pichichero M.E.
        A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients.
        Pediatrics. 2005; 115: 1048-1057
        • Antunez C.
        • Blanca-Lopez N.
        • Torres M.J.
        • et al.
        Immediate allergic reactions to cephalosporins: evaluation of cross-reactivity with a panel of penicillins and cephalosporins.
        J Allergy Clin Immunol. 2006; 117: 404-410
        • Atanaskovic-Markovic M.
        • Velickovic T.C.
        • 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
        • Park M.
        • Markus P.
        • Matesic D.
        • Li J.T.
        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
        • Dhar H.L.
        • Kulkarni D.N.
        Cross reactivity of cephalosporins with penicillin.
        Indian J Physiol Pharmacol. 1994; 38: 303-305
        • Assem E.S.
        • Vickers M.R.
        Immunological response to penicillamine in penicillin-allergic patients and in normal subjects.
        Postgrad Med J. 1974; 50: 65-71
        • Solley G.O.
        • Gleich G.J.
        • Van Dellen R.G.
        Penicillin allergy: clinical experience with a battery of skin-test reagents.
        J Allergy Clin Immunol. 1982; 69: 238-244
        • DePestel D.D.
        • Benninger M.S.
        • Danziger L.
        • et al.
        Cephalosporin use in treatment of patients with penicillin allergies.
        J Am Pharm Assoc (2003). 2008; 48: 530-540