A word about cephalosporin use and cross-reactivity

Misdiagnosis of β-lactam allergies and misunderstanding of cross-reactivity among β-lactams often leads to suboptimal antibiotic choices, namely broader spectrum antibiotics with worse safety and efficacy profiles

There is ample evidence that essentially all cephalosporins (aside from a few early generation ones) are safe to use in patients with penicillin or amoxicillin allergies. Patients with penicillin allergies do have a general elevated risk of allergic reactions, but not specifically to cephalosporins

If there is a true cross-reactivity between penicillins and cephalosporins, it is related to its biochemical R1 side chain. For that reason, clinicians should be cognizant of R1 side chain similarities when considering alternate beta-lactams in allergic individuals

Therefore, virtually every patient reporting a history of or who is skin test positive to penicillins may receive a cephalosporin antibiotic as a replacement with the exception of those showing R1 side-chain similarity

The Bottom Line

Penicillin-allergic patients do NOT have to avoid all cephalosporins. Cross-reactivity is exceptionally rare, and occurs only when there is similarity in R1 side chains

For example: in patients with a penicillin allergy, cefazolin, ceftriaxone, and meropenem all have dissimilar R1 side chains and have rates of adverse reactions similar to the general public

***The risks of medicolegal prosecution are always a concern for clinicians and part of the decision-making paradigm. It should be recognized that patients with a bona fide allergy to a β-lactam antibiotic may experience an allergic reaction to a different β-lactam antibiotic as an independent hypersensitivity reaction, that is not related by cross-reactivity***

References

1. Marcos Bravo C, Luna Ortiz I, Gonzalez Vazquez R. Hypersensitivity to cefuroxime with good tolerance to other betalactams. Allergy. 1995;50:359-61.

2. Igea JM, Fraj J, Davila I, Cuevas M, Cuesta J, Hinojosa M. Allergy to cefazolin: study of in vivo cross reactivity with other betalactams. Ann Allergy. 1992;68:515-9.

3. Romano A, Quaratino D, Venuti A, Venemalm L, Mayorga C, Blanca M. Selective type-1 hypersensitivity to cefuroxime. J Allergy Clin Immunol. 1998;101:564-5.

4. Romano A, Quaratino D, Venemalm L, Torres MJ, Venuti A, Blanca M. A case of IgE-mediated hypersensitivity to ceftriaxone. J Allergy Clin Immunol. 1999;104:1113-4.

5. Poston SA, Jennings HR, Poe KL. Cefazolin tolerance does not predict ceftriaxone hypersensitivity: unique side chains precipitate anaphylaxis. Pharmacotherapy. 2004;24:668-72.

6. Romano A, Valluzzi RL, Caruso C, Maggioletti M, Quaratino D, Gaeta F. Cross-Reactivity and Tolerability of Cephalosporins in Patients with IgE-Mediated Hypersensitivity to Penicillins. J Allergy Clin Immunol Pract. 2018.

7. Romano A, Gaeta F, Valluzzi RL, et al. IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of alternative cephalosporins. J Allergy Clin Immunol. 2015;136:685-91 e3.

8. David A. Khan, Aleena Banerji, Kimberly G. Blumenthal, Elizabeth J. Phillips, Roland Solensky, Andrew A. White, Jonathan A. Bernstein, Derek K. Chu, Anne K. Ellis, David BK. Golden, Matthew J. Greenhawt, Caroline C. Horner, Dennis Ledford, Jay A. Lieberman, John Oppenheimer, Matthew A. Rank, Marcus S. Shaker, David R. Stukus, Dana Wallace, Julie Wang, Drug Allergy: A 2022 Practice Parameter Update, Journal of Allergy and Clinical Immunology, 2022, https://doi.org/10.1016/j.jaci.2022.08.028

A word about cephalosporin use and cross-reactivity

Side Chain Chart

The Bottom Line

References

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