What is the prevalence of Cephalexin (Keflex) allergy?

From the Guidelines

Cephalexin allergy prevalence is estimated to be around 5.3% in patients with a proven penicillin allergy.

Key Points

• The risk of cross-reactivity between penicillins and cephalosporins is generally low, but may be higher for cephalosporins with similar side chains to the culprit penicillin 1.
• A meta-analysis found that the risk of cross-reactivity to cephalosporins in patients with proven penicillin allergy varied from 16.45% for aminocephalosporins (such as cephalexin) to 2.11% for low-similarity-score cephalosporins 1.
• Cephalexin has a similar side chain to some penicillins, which may increase the risk of cross-reactivity in patients with a penicillin allergy 1.
• The estimated risk of cross-reactivity for cephalexin is around 5.3% in patients with a proven penicillin allergy 1.
• Skin testing may be useful for patients with a history of anaphylactic or convincing histories of IgE-mediated reactions to cephalexin, but its validity and sensitivity are unknown 1.
• A negative skin test should be followed by a drug challenge to confirm tolerance 1.
• The reaction rate to cefazolin among patients with an unverified penicillin allergy is 0.7% (95% CrI: 0.1%-1.7%) 1, but cefazolin has a unique side chain and appears to have very low cross-reactivity with penicillins despite being a first-generation cephalosporin 1.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEPHALEXIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALEXIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

The prevalence of Cephalexin (Keflex) allergy is not directly stated in the drug label. However, it is mentioned that cross-hypersensitivity among beta-lactam antibiotics, including cephalexin, may occur in up to 10% of patients with a history of penicillin allergy 2.

From the Research

Prevalence of Cephalexin (Keflex) Allergy

• The prevalence of cephalosporin allergy, including Cephalexin, is estimated to be around 1-3% of the population 3.
• A study found that the overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 4.
• Cephalexin, a first-generation cephalosporin, has been reported to have a modest cross-allergy with penicillins 5, 6.
• A prospective study found that 37.7% of patients with IgE-mediated hypersensitivity to penicillins had positive allergy tests for aminocephalosporins, including cephalexin, which share similar or identical side chains with penicillins 7.

Risk Factors and Cross-Reactivity

• Risk factors for cephalosporin allergies include female sex, advanced age, and a history of another antibiotic or penicillin allergy 3.
• The cross-reactivity potential of cephalosporins is related to the structural R1 side chain, and clinicians should be cognizant of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals 3, 4, 5.
• Cephalosporins with dissimilar side chains to the offending penicillin carry a negligible risk of cross-allergy 4, 6, 7.

Clinical Implications

• Clinicians should consider the low likelihood of true cephalosporin allergy when clinically indicated 3.
• The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin may be safe in penicillin-allergic patients 4, 6, 7.
• Skin testing and serum specific IgE assays may be useful in evaluating the cross-reactivity of cephalosporins in patients with IgE-mediated hypersensitivity to penicillins 7.