From the Guidelines
Cephalexin should be used with caution in patients with a penicillin allergy, as the cross-reactivity between penicillins and cephalosporins is estimated to be around 2-4.8%. According to the most recent study from 2022, published in the Journal of Allergy and Clinical Immunology 1, the cross-reactivity between penicillins and cephalosporins is lower than previously thought. The study suggests that early estimates of cross-reactivity were falsely high due to contamination of cephalosporins with penicillins before 1980.
Key Considerations
- The risk of cross-reactivity is higher in patients with a history of severe, immediate allergic reactions to penicillin, such as anaphylaxis, hives, or swelling.
- Patients with a mild penicillin allergy, such as a delayed rash, may be able to tolerate cephalexin under medical supervision.
- It is essential to inform healthcare providers about any penicillin allergy before taking cephalexin, as they may need to prescribe an alternative antibiotic from a different class.
Alternative Antibiotics
- Macrolides (e.g., azithromycin)
- Fluoroquinolones (e.g., ciprofloxacin)
- Tetracyclines (e.g., doxycycline)
Important Notes
- Cephalexin skin testing may be useful for patients with anaphylactic or convincing histories of IgE-mediated reactions, but its validity and sensitivity are unknown 1.
- A positive cephalosporin skin test suggests drug-specific IgE antibodies, and the patient should receive a skin test–negative alternative cephalosporin or alternate antibiotic, or undergo desensitization 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.
Cephalexin is not necessarily okay with penicillin allergy. Caution should be exercised when giving cephalexin to patients with a history of penicillin allergy due to the possibility of cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2.
From the Research
Cephalexin and Penicillin Allergy
- Cephalexin is a first-generation cephalosporin, and its use in penicillin-allergic patients has been a topic of discussion due to the potential for cross-reactivity 3, 4, 5.
- Studies have shown that the cross-reactivity between penicillins and cephalosporins is lower than previously reported, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
- However, cephalexin has been reported to confer an increased risk of allergic reaction among patients with penicillin allergy, although the risk is still considered to be relatively low 4, 5.
Cross-Reactivity and Allergic Reactions
- The R1 side chain is responsible for the cross-reactivity between penicillins and cephalosporins, and laboratory and cohort studies have confirmed this association 3.
- A study reported that cefadroxil, a first-generation cephalosporin, had a high prevalence of cross-reactivity with penicillins, with a rate of 27% 3.
- Another study found that cephalexin, cefazolin, and cefadroxil increased the risk of allergic reactions in penicillin-allergic patients, while cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone did not increase this risk 4.
Safe Use of Cephalosporins in Penicillin-Allergic Patients
- Third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains to the offending penicillin can be used safely in penicillin-allergic patients, with a negligible risk of cross-allergy 3, 5.
- A study suggested that obtaining a detailed history of antibiotic allergy, allergy testing, and/or direct oral challenge can help de-label unsubstantiated penicillin or cephalosporin allergy and ultimately reduce the incidence of surgical site infections by optimizing the use of more effective antibiotics 6.