β-lactam allergy

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Β-lactam allergy /
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Cross-Reactivity

  • 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
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)

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

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.
  2. ^  Anna R. Wolfson, Emily M. Huebner, Kimberly G. Blumenthal. Acute care beta-lactam allergy pathways: approaches and outcomes. Annals of Allergy, Asthma & Immunology. 2019;123(1):16-34. doi:10.1016/j.anai.2019.04.009.