Cephalosporin Allergy Assessment

Criteria & Principles

^{Disclamer: While the information below is based on current evidenced-based literature, the interpretation of cephalosporin immunogenicity and cross-reactivity may vary as new research emerges. Therefore, clinical judgement should be used in conjuction with the information presented.}

Epidemiology^1-2

Cephalosporins are among the most prescribed antibiotics in the United States and are often unnecessarily avoided in patients with penicillin allergies

MYTH 1: Cephalosporins should be avoided with a penicillin allergy

• Historic cross-reactivity between cephalosporins and penicillin was overestimated due to early cephalosporin antibiotics containing trace amounts of penicillin
• Actual cross-reactivity between 2nd and 3rd generation cephalosporins in penicillin-proven allergy patients is ~1%.

MYTH 2: Dual cephalosporin and penicillin allergies are common

• Dual allergy with cefazolin and penicillin is rare (0.7%) and most patients with a reported penicillin allergy will tolerate cefazolin
  • For other cephalosporins, comparing side chains can be used as a tool to predict the likelihood of cross reactivity
• The DUHS Adult Surgical Antibiotic Prophylaxis Charts have been updated to reflect administration of cefazolin for surgical prophylaxis, where indicated, for patients with penicillin allergy
  • EXCEPTIONS: alternative regimens are recommended for patients with history of confirmed cefazolin allergy, anaphylaxis to any cephalosporins, or high-risk penicillin/cephalosporin allergies (e.g., SCAR, history of kidney or liver injury)

MYTH 3: Non-β-lactam alternatives are as safe and effective as β-lactam therapy for most infections

• Patients experience worse outcomes and higher adverse events when alternative antimicrobials (e.g. clindamycin, aztreonam, fluoroquinolones, vancomycin) are utilized

MYTH 4: Allergy assessments are difficult

• Allergy histories are SIMPLE & required for all patients!!  Adequate characterization of the allergy through patient interview is simple but critical – check out our penicillin allergy assessment tool to guide allergy histories.

Importance of R1 Side Chains^1,3

• Cephalosporin immunogenicity & cross-reactivity is primarily driven by R1 side chains, and studies suggest that patients most often tolerate cephalosporins with a different R1 group/side chain
• In a study of 102 patients with immediate allergic reactions to cephalosporins (89 of which were anaphylaxis), 91% of cephalosporin allergies were found to be based on side-chain structure. The other 9% showed skin test reactivity to cephalosporin groups with dissimilar R1 side chains, suggesting there may be other factors involved

Management of Cephalosporin Allergies⁴

Figure 1: Consideration for β-lactam use in adult patients with prior penicillin or cephalosporin allergy (Khan parameter update)

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Table 1. β-Lactam Cross-Reactivity Chart 

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^{Note: Risk is stratified based on the likelihood for cross reactivity, NOT the severity risk of the reaction}

β-lactam Allergy & Carbapenems or Aztreonam⁴

• In patients with a reported penicillin or cephalosporin allergy, carbapenems may be administered without additional testing
• In patients with a reported penicillin or cephalosporin allergy, aztreonam may be administered without testing
  • EXCEPTION: ceftazidime or cefiderocol allergy, given identical R1 side chain

Questions? Page or secure chat your friendly, neighborhood ASET PharmD at 970-6666.  Click here for more info about our team. We’re here to help!

References

1. ^{Khan DA, et al. Cephalosporin Allergy: Current Understanding and Future Challenges. J Allergy Clin Immunol Pract 2019;7(7):2105-2114. doi: 10.1016/j.jaip.2019.06.001.}
2. ^{Chaudhry SB, et al. Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity. Pharmacy (Basel) 2019;7(3):103. doi: 10.3390/pharmacy7030103.}
3. ^{Romano A, et al. IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of alternative cephalosporins. J Allergy Clin Immunol 2015;136(3):685–91 e3. doi: 10.1016/j.jaci.2015.03.012.}
4. ^{Khan DA, et al. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol 2022;150(6):1333-1393. doi: 10.1016/j.jaci.2022.08.028.}
5. ^{Picard M, et al. Cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients: two systematic reviews and meta-analyses. J Allergy Clin Immunol Practi 2019;7:2722-38.e5. doi: 10.1016/j.jaip.2019.05.038.}
6. ^{Sousa-Pinto B, et al. Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin: A Systematic Review and Meta-analysis. JAMA Surg 2021;156(4):e210021. doi: 10.1001/jamasurg.2021.0021.}
7. ^{Chaudhry SB, Veve MP, Wagner JL. Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity. Pharmacy (Basel). 2019;7(3):103. Published 2019 Jul 29.}