Penicillin/Cephalosporin Cross-Reactivity - Indiana
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
- CDC Website. https://www.cdc.gov/antibiotic-use/community/for-hcp/Penicillin-Allergy.html
- 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.
- Gonzalez-Estrada A, Radojicic C. Penicillin allergy: a practical guide for clinicians. Cleve Clin J Med. 2015 May;82(5):295-300.
- Bernstein JA. Update on angioedema: evaluation, diagnosis, and treatment. Allergy Asthma Proc 2011; 32(6):408-412.
- 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.
- 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.
- Macy E, Ngor E. Recommendations for the management of beta-lactam intolerance. Clinical Rev Allerg Immunol. 2014; 47:46-55.
- 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.
- Zagursky RJ, Pichichero ME. Cross- reactivity in B-lactam allergy. J Allergy Clin Immunol Pract. 2018; 6: 72-81.
- Ledford DK. Cephalosporin side chain cross-reactivity. J Allergy Clin Immunol Pract. 2015; 3(6): 1006-7.