β-lactam allergy

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Β-lactam allergy /
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Hypersensitivity Reactions

  • Type I (IgE-mediated)
    • Anaphylaxis
    • Itchy rash
    • Penicillins should be avoided
  • Type II (IgG-mediated)
    • Non-itchy rash
    • Rash will improve if treatment continues, no need to avoid penicillins
  • Type IV (cell-mediated)
    • Toxic epidermal necrolysis
    • Stevens-Johnson syndrome
    • Penicillins should be avoided

Cross-Reactivity

  • The following applies to immediate, IgE-mediated hypersensitivity reactions
  • Cross-reactivity within penicillins is mediated by homology of the R1 side chain (referring to the C6 side chain) and by the β-lactam ring itself
  • Cross-reactivity between penicillins and cephalosporins is mediated by homology of the R1 side chains (referring to the C6 side chain in penicillins or the C7 side chain in cephalosporins)
  • Cross-reactivity within cephalosporins is mediated both by homology of the R1 side chains and also R2 side chains (referring to the C3 side chain)
  • There is very low (~2%) cross-reactivity between penicillin allergy and carbapenems1
Antibiotic R1 R2
G1 G2 G3 G1 G2 G3 G4 G5 G6 G7
Penicillins
Penicillin X
Ampicillin X
Amoxicillin X
First-Generation Cephalosporins
Cefazolin
Cephalexin X X
Cefadroxil X X
Cephalothin X X
Second-Generation Cephalosporins
Cefotetan X
Cefoxitin X X
Cefuroxime X
Cefaclor X
Third-Generation Cephalosporins
Cefotaxime X X
Ceftriaxone X
Ceftazidime X
Cefixime X
Cefdinir
Fourth-Generation Cephalosporins and Higher
Cefipime X
Ceftaroline

R1 Side Chains (C6 and C7)

R2 Side Chains (C3)

Management

Penicillin Allergy

  • Consider skin testing
Class Cross-reactivity Notes
Cephalosporin, 1st generation 2-8% Based on poor studies. Avoid cephalexin and cefaclor in ampicillin allergy.
Cephalosporin, 2nd generation 2% Avoid cefoxitin in penicillin allergy. Avoid cefadroxil and cefprozil in amoxicillin allergy.
Cephalosporin, 3rd generation <1% Generally considered safe.
Cephalosporin, higher generation N/A No data available, but generally considered safe.
Carbapenem 1% Generally considered safe.
Monobactam <1% Avoid aztreonam in ceftazidime allergy.
  • For those with penicillin allergy
    • 1st gen cephalosporins: cross-reactavoid cephalexin and cefaclor if ampicillin allergic
    • 2nd gen cephalosporins:

Further Reading

  • Cross-reactivity in β-Lactam Allergy. J Allergy Clin Immunol Pract. 2018;6(1):72-81.e1. doi: 10.1016/j.jaip.2017.08.027
  • Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses. J Allergy Clin Immunol Pract. 2019;7(8):2722-2738.e5. doi: 10.1016/j.jaip.2019.05.038

References

  1. ^  Brittany Kula, Gordana Djordjevic, Joan L. Robinson. A Systematic Review: Can One Prescribe Carbapenems to Patients With IgE-Mediated Allergy to Penicillins or Cephalosporins?. Clinical Infectious Diseases. 2014;59(8):1113-1122. doi:10.1093/cid/ciu587.