Cephalexin Recommended for Dermatologic Surgery with Penicillin Allergy

The American Society for Dermatologic Surgery’s advisory statement, published on August 6, 2025, recommends cephalexin as the first-line prophylactic antibiotic in dermatologic surgery for patients with documented penicillin allergy.1

Approximately 10% of US patients report a penicillin allergy.2 A meta-analysis assessing penicillin allergy prevalence across 28 countries found that high-income countries had a greater prevalence of penicillin allergy than middle-income countries. High-income countries had a 9.9% prevalence of penicillin allergy (95% confidence interval [CI], 8.7 – 11.0%), compared with a 4.4% penicillin allergy prevalence in middle-income countries (95% CI, 2.8 – 6.2%) (P < .0001).3

The US may have 10% of patients with documented penicillin allergy, but reports have shown that when evaluated for IgE-mediated reactions, such as hives, angioedema, wheezing, and anaphylaxis, 90% of patients do not have a true allergy.2 The Centers for Disease Control & Prevention (CDC) reported that 80% of patients with IgE-mediated penicillin lose their sensitivity after 10 years.4

According to Mayo Clinic, patients allergic to 1 type of penicillin may be allergic to other types of penicillin (amoxicillin, ampicillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, ticarcillin) or some cephalosporins (cefaclor, cefadroxil, cefazolin, cefdinir, cefepime, cefotetan, cefprozil, cefuroxime, cephalexin), although this is not always the case.5

Previous guidelines have stated that patients with a penicillin allergy should receive an alternative to cephalexin for prophylaxis in dermatologic surgery. However, since then, it was reported that only 4% of individuals with a reported penicillin allergy are confirmed to be hypersensitive to cephalexin.6

In December 2017, Kaiser Permanente Southern California removed all warnings in its electronic health record systems advising against the use of cephalexin in the setting of a penicillin allergy.6 Other healthcare providers followed along, removing the warning. Nearly 8 years later, no guidelines have been established for the cephalexin use in patients with a penicillin allergy.

“Setting standards for cephalosporin use among penicillin-allergic patients… is important to the quality and safety of care we deliver,” Kimberly G. Blumenthal, MD, MSc, from Massachusetts General Hospital, told HCPLive’s sister site, Contagion, at the 2017 American Academy of Allergy, Asthma, and Immunology (AAAAI) meeting.7

Still, even though many healthcare providers removed the warning, investigators sought to determine if cephalexin should be the first-line prophylactic antibiotic in dermatologic surgery for patients with penicillin allergy.1 The team, led by Elliott Campbell, MD, FAAD, from the Dermatology Associates of Northern Kentucky, investigated this by conducting a systematic review.

The literature shows that patients with true, persistent penicillin allergy have an overall low cross-reactivity with cephalosporins. This is particularly low among cephalosporins that do not share an identical R1 side chain. The first-generation cephalosporins, including cephalexin, have a slightly greater risk of cross-reactivity in patients with reported allergy to aminopenicillin, including amoxicillin and ampicillin, but not to other penicillins.

A study back in 2012 reported that the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins (odds ratio 4.8; 95% confidence interval [CI], 3.7 to 6.2).8 Data confirms that the R1 side chain is responsible for this cross-reactivity.8

Patients with low-risk penicillin allergies have extremely low risks of severe cross-reactivity of cephalosporins.1 Compared with other cephalosporins, cephalexin has a superior efficacy and safety profile.

“Cephalexin should be used as the first-line prophylactic antibiotic in dermatologic surgery for patients with documented penicillin allergy, including anaphylaxis,” investigators concluded.1“There may be a higher risk of cross-reactivity with cephalexin in patients with a confirmed amino-penicillin allergy.”

References

1. Campbell E, Virk A, Gonzalez-Estrada A, Lessard S, Otley C. The Use of Perioperative Cephalexin in Penicillin Allergic Patients in Dermatologic Surgery: An Advisory Statement. Dermatol Surg. Published online August 6, 2025. doi:10.1097/DSS.0000000000004784

2. Patterson R and Stankewicz H. Penicillin Allergy. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK459320/. Accessed August 15, 2025.

3. Derman, C. Penicillin Allergy Prevalence Greater in High-Income vs. Middle-Income Nations. HCPLive. January 28, 2025. https://www.hcplive.com/view/penicillin-allergy-prevalence-greater-high-income-vs-middle-income-nations. Accessed August 18, 2025.

4. Clinical Features of Penicillin Allergy. CDC. April 22, 2024. https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html. Accessed August 18, 2025.

5. Penicillin Allergy. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/penicillin-allergy/symptoms-causes/syc-20376222. Accessed August 15, 2025

6. Cephalosporins OK when there is a claimed penicillin allergy. American Academy of Allergy, Asthma, & Immunology. October 28, 2021. https://www.aaaai.org/tools-for-the-public/latest-research-summaries/the-journal-of-allergy-and-clinical-immunology-in/2021/cephalosporins. Accessed August 15, 2025.

7. Dunleavy, B. Cephalosporin Use in Penicillin-Allergic Patients: Pros & Cons. ContagionLive. October 3, 2017. https://www.contagionlive.com/view/cephalosporin-use-in-penicillin-allergic-patients-pros-cons. Accessed August 15, 2025.

8. Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: a literature review. J Emerg Med. 2012;42(5):612-620. doi:10.1016/j.jemermed.2011.05.035