Penicillin/Cephalosporin Cross-Reactivity - Indiana

by S. Kelly last updated Feb 08, 2021 08:37 PM

Indiana State Department of Health

Healthcare professionals often overestimate cross-reactivity between Penicillins and Cephalosporins. The mechanism of cross-reactivity was previously believed to be related to a common β-lactam ring, but new evidence suggests it is instead related to the sharing of identical R-group side chains.

  • Risk of cross-reactivity between penicillins/cephalosporins and within cephalosporin class is highest with IDENTICAL R1/R2 side chains
  • Caution is warranted for agents with similar R1/R2 side chains if history of life-threatening or severe reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, interstitial nephritis, hemolytic anemia
  • Carbapenems and aztreonam have sufficiently dissimilar structures from penicillins/cephalosporins and are not expected to cross-react (exception = aztreonam with ceftazidime or cefiderocol)
  • Patients may experience an independent allergic reaction to a different β-lactam unrelated to cross-reactivity
  IDENTICAL R1/R2 side chains
– highest risk of cross-reactivity		 Similar R1/R2 side chains – low risk of cross-reactivity
but caution if history of life-threatening reaction
Ampicillin* CEPHALEXIN, CEFACLOR Cefadroxil, cefprozil
Amoxicillin* CEFADROXIL, CEFPROZIL Cephalexin, cefaclor
Cefaclor AMPICILLIN, CEPHALEXIN Penicillin, piperacillin, amoxicillin, cefadroxil, cefprozil
Cefadroxil AMOXICILLIN, CEFPROZIL Penicillin, piperacillin, ampicillin, cephalexin, cefaclor
Cefazolin NONE NONE
Cefdinir CEFIXIME Ceftibuten, ceftriaxone, cefotaxime, cefpodoxime, ceftazidime,
cefepime, ceftaroline, ceftolozane, cefiderocol
Cefepime CEFTRIAXONE, CEFOTAXIME,
CEFPODOXIME		 Cefuroxime, ceftibuten, cefdinir, cefixime, ceftazidime,
ceftaroline, ceftolozane, cefiderocol
Cefixime CEFDINIR Cefuroxime, ceftibuten, ceftriaxone, cefotaxime, cefpodoxime,
ceftazidime, cefepime, ceftaroline, ceftolozane, cefiderocol
Cefoxitin CEFUROXIME Cefotaxime
Cefpodoxime CEFTRIAXONE, CEFEPIME,
CEFOTAXIME		 Cefuroxime, ceftibuten, cefdinir, cefixime, ceftazidime,
ceftaroline, ceftolozane, cefiderocol
Cefprozil AMOXICILLIN, CEFADROXIL Penicillin, piperacillin, ampicillin, cephalexin, cefaclor
Ceftaroline NONE Cefuroxime, ceftibuten, cefdinir, cefixime, ceftriaxone, cefotaxime,
cefpodoxime, ceftazidime, cefepime, ceftolozane, cefiderocol
Ceftazidime AZTREONAM, CEFIDEROCOL

Ceftibuten, cefdinir, cefixime, ceftriaxone, cefotaxime,

cefpodoxime, cefepime, ceftaroline, Ceftolozane
Ceftibuten NONE Cefdinir, cefixime, ceftriaxone, cefotaxime, cefpodoxime,
ceftazidime, cefepime, ceftaroline, ceftolozane, cefiderocol
Ceftolozane NONE Ceftibuten, cefdinir, cefixime, ceftriaxone, cefotaxime,
cefpodoxime, ceftazidime, cefepime, ceftaroline, cefiderocol
Ceftriaxone CEFEPIME, CEFOTAXIME,
CEFPODOXIME		 Cefuroxime, ceftibuten, cefdinir, cefixime, ceftazidime,
ceftaroline, ceftolozane, cefiderocol
Cefuroxime CEFOXITIN Cefixime, ceftriaxone, cefotaxime, cefpodoxime, cefepime,
ceftaroline
Cephalexin AMPICILLIN, CEFACLOR Penicillin, piperacillin, amoxicillin, cefadroxil, cefprozil
Penicillin G*   Cefadroxil, cephalexin, cefprozil, cefaclor

Adapted from Zagursky RJ. J Allergy Clin Immunol Pract. 2018.
Excludes cephalosporins that have been discontinued or are rarely used (ex = cephalothin, cefamandole, cefoperazone)
*For penicillins, chart only addresses cross-reactivity with cephalosporins. Avoid other penicillins in true penicillin allergy.

References

  1. CDC Website. https://www.cdc.gov/antibiotic-use/community/for-hcp/Penicillin-Allergy.html
  2. Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273.
  3. Gonzalez-Estrada A, Radojicic C. Penicillin allergy: a practical guide for clinicians. Cleve Clin J Med. 2015 May;82(5):295-300.
  4. Bernstein JA. Update on angioedema: evaluation, diagnosis, and treatment. Allergy Asthma Proc 2011; 32(6):408-412.
  5. Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A et al. Second symposium on the definition and management of anaphylaxis: summary report–second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med. 2006; 47:373-380.
  6. Blumenthal KG, Shenoy ES, Hurwitz S, Varughese CA, Hooper DC, Banerji A. Effect of a drug allergy educational program and antibiotic prescribing guideline on inpatient clinical providers’ antibiotic prescribing knowledge. J Allergy Clin Immunol. 2014;2(4):407-412.
  7. Macy E, Ngor E. Recommendations for the management of beta-lactam intolerance. Clinical Rev Allerg Immunol. 2014; 47:46-55.
  8. Pichichero, ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr; 115(4):1048-1057.
  9. Zagursky RJ, Pichichero ME. Cross- reactivity in B-lactam allergy. J Allergy Clin Immunol Pract. 2018; 6: 72-81.
  10. Ledford DK. Cephalosporin side chain cross-reactivity. J Allergy Clin Immunol Pract. 2015; 3(6): 1006-7.