All Pharmacy Pearls

Introduction

  • Only 0.5% to 2% of patients with a documented penicillin allergy that are administered a penicillin

    • will exhibit a hypersensitivity reaction, usually presenting as a rash or hives.

  • True IgE-mediated penicillin allergies that cause anaphylaxis are rare.
  • An IgE-mediated penicillin allergy can diminish over time, as 80% of patients become tolerant after

    • a decade.

  • Patients with a documented penicillin allergy may be inappropriately exposed to alternative

    • antibiotics, resulting in increased treatment failures, adverse effects, and antimicrobial resistance.

  • Penicillins, cephalosporins, and carbapenems all share a beta-lactam core structure, thus raising

    • the potential for cross-reactivity among these agents.

Clinical Detail

    Group 1

    Group 2

    Group 3

    Group 4

    Penicillin

    Cefoxitin

    Cefuroxime

    Amoxicillin

    Ampicillin

    Cefaclor

    Cephalexin

    Cefadroxil

    Ceftriaxone

    Cefotaxime

    Cefuroxime

    Cefepime

    Cefpodoxime

    Ceftaroline

    Aztreonam

    Ceftolazane

    Ceftazidime

  • The following drugs in each group

    • may have cross-reactivity to each

    other due to similar side chains

  • Cross-reactivity between penicillins

    • and cephalosporins is about 2%

  • Cefazolin is NOT likely to cross react

    • with penicillin (side chains NOT similar)

  • Cross-reactivity with monobactams

    • (i.e. aztreonam) is negligible

  • Cross-reactivity between penicillins

    • and carbapenems is <1%

Evidence

    Author

    Design

    Intervention & Comparison

    Outcome

    Why Cross-Reactivity?

    Nagakura,

    1990

    Mayorga,

    1995

    Animal study

  • Studied antibodies formed

    • when animals were immunized

    with protein-beta-lactam

    conjugates

  • 92% of the antibodies recognized an epitope in

    • which the side chain was the main constituent

  • The side chain is the most important

    • determinant in penicillin immunogenicity

    Cephalosporins

    Goodman,

    2001

    Retrospective

    review

    (n=2933)

  • Orthopedic patients with

    • penicillin allergy receiving

    cefazolin prior to a procedure

  • Only 1 patient may have had an allergic

    • reaction to cefazolin

  • Cross-reactivity rate with cefazolin was 0.33%

    • Daulat,

    2004

    Retrospective

    review

    (n=606)

  • Patients with penicillin allergy

    • receiving cephalosporins

  • 42% 1st gen., 21% 2nd gen., and

    • 37% 3rd or 4th gen.

    cephalosporins

  • Only 1 patient had an allergic reaction that

    • was documented as worsening of underlying

Conclusions

  • True penicillin allergies are less common than reported, and anaphylaxis is uncommon.
  • Cross-reactivity among penicillins and cephalosporins is attributed to similarity in side chains.
  • Cephalosporin cross-reactivity with penicillins is much lower than reported in early studies partly due

    • to contamination of study drugs with penicillin.

  • Cross-reactivity between cephalosporins is about 2% and with carbapenems is <1%.

References

  • Apter AJ, Kinman JL, Bilker WB, et al. Is There Cross-Reactivity Between Penicillins and Cephalosporins? Am J

    • Med. 2006;119(4):354e11-19.

  • Atanaskovic-Markovic M, Gaeta F, Medjo B, Viola M, Nestorovic B, Romano A. Tolerability of Meropenem in

    • Children with IgE-Mediated Hypersensitivity to Penicillins. Allergy. 2008;63:237-240.

  • Blumenthal KG, Shenoy ES, Wolfson AR, et al. Addressing Inpatient Beta-Lactam Allergies: A Multihospital

    • Implementation. J Allergy Clin Immunol Pract. 2017;5(3):616-625.

  • Blumenthal KG, Huebner EM, Fu X, et al. Risk-Based Pathway for Outpatient Penicillin Allergy Evaluations. J

    • Allergy Clin Immunol Pract. 2019;7(7):2411-2414.

  • Campagna JD, Bond MC, Schabelman E, Hayes BD. The Use of Cephalosporins in Penicillin-Allergic Patients: A

    • Literature Review. J Emerg Med. 2012;42(5):612-620.

  • Chaudry SB, Veve MP, Wagner JL. Cephalosporins: A Focus on Side Chains and Beta-Lactam Cross-Reactivity.

    • Pharmacy. 2019;7:1-16.

  • Daulat S, Solensky R, Earl HS, Casey W, Gruchalla RS. Safety of Cephalosporin Administration to Patients with

    • Hstories of Penicillin Allergy. J Allergy Clin Immunol Pract. 2004;113(6):1220-1222.

  • DePestel DD, Benninger MS, Danziger L, et al. Cephalosporin Use in Treatment of Patients with Penicillin

    • Allergies. J Am Pharm Assoc. 2008;48:530-540.

  • Goodman EJ, Morgan MJ, Johnson PA, Nichols BA, Denk N, Gold BB. Cephalosporins can be Given to

    • Penicillin-Allergic Patients Who Do Not Exhibit an Anaphylactic Response. J Clin Anesth. 2001;13(8):561-564.

  • Mayorga C, Obispo T, Jimeno L, et al. Epitope Mapping of Beta-Lactam Antibiotics with the Use of

    • Monoclonal Antibodies. Toxicology. 1995;97:225-234.

  • Nagakura N, Souma S, Shimizu T, Yanagihara Y. Anti-Ampicillin Monoclonal Antibodies and their Cross-

    • Reactivities to Various Beta-Lactams. Br J Hosp Med. 1990;44:252-258.

  • Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Pettinato R, Gueant JL. Imipenem in Patients with

    • Immediate Hypersensitivity to Penicillins. N Engl J Med. 2006;354:2835-2837.

  • Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Valluzzi R, Gueant JL. Brief Communication: Tolerability of

    • Meropenem in Patients with IgE-Mediated Hypersensitivity to Penicillins. Ann Intern Med. 2007;146:266-269.

  • Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review.

    • JAMA. 2019;321(2):188-199.

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