Can a patient with a hypersensitivity to cefixime (a third-generation cephalosporin) take cephalexin (a first-generation cephalosporin)?

From the Guidelines

Patients with a hypersensitivity to cefixime should avoid cephalexin if they have a severe or anaphylactic reaction, but those with a mild reaction may tolerate cephalexin under medical supervision, as the risk of cross-reactivity is low, especially if the side chains are dissimilar, as suggested by the most recent study 1.

Key Considerations

• The risk of cross-reactivity between cephalosporins is generally low, especially if the side chains are dissimilar, with studies suggesting a cross-reactivity rate of around 2% 1.
• Patients with a history of anaphylaxis to cephalosporins should undergo penicillin skin testing and drug challenge before receiving penicillin therapy, as recommended by a 2022 practice parameter update 1.
• The Dutch Working Party on Antibiotic Policy guideline recommends that patients with a suspected immediate-type allergy to cephalosporins can receive cephalosporins with dissimilar side chains, irrespective of severity and time since the index reaction, with a strong recommendation and moderate quality of evidence 1.

Recommendations

• Patients with a mild reaction to cefixime may be able to tolerate cephalexin under medical supervision, with careful evaluation of their allergy history and consideration of skin testing if appropriate.
• Alternative antibiotic classes like penicillins, macrolides, fluoroquinolones, or others may be recommended depending on the infection being treated and the patient's complete medical history.
• Patients with a severe or anaphylactic reaction to cefixime should generally avoid all cephalosporins, including cephalexin, due to the risk of cross-reactivity.

Important Notes

• The allergic reaction is often related to the specific side chain of the molecule rather than the core structure, which is why dissimilar side chains may reduce the risk of cross-reactivity.
• Consultation with a healthcare provider is essential to evaluate the patient's specific allergy history and determine the best course of action.

From the Research

Cephalosporin Cross-Reactivity

• Cephalosporins are a class of antibiotics with a wide range of clinical utility and general tolerability, but there is a potential for cross-reactivity among different generations of cephalosporins 2.
• The cross-reactivity potential is related to the structural R1 side chain, and clinicians should be aware of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals 2, 3.
• First-generation cephalosporins, such as cephalexin, have a higher cross-reactivity with penicillins compared to later-generation cephalosporins, such as cefixime 3, 4.

Hypersensitivity to Cefixime and Cephalexin

• A patient with a hypersensitivity to cefixime (a third-generation cephalosporin) may still be able to take cephalexin (a first-generation cephalosporin), but the risk of cross-reactivity should be considered 4, 5.
• 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.
• However, the risk of cross-reactivity may be higher for certain cephalosporins, such as cefadroxil, which has been reported to have a cross-reactivity rate as high as 27% 4.

Diagnosis and Management of Cephalosporin Hypersensitivity

• Diagnosis of cephalosporin hypersensitivity can be made through skin testing or drug provocation testing, and the results can guide the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure 5, 6.
• Cephalosporin hypersensitivity can manifest as immediate or non-immediate reactions, and anaphylaxis is a common presentation 6.
• Cross-reactivity with aminopenicillins is a common pattern of cross-reactivity in cephalosporin hypersensitive patients 6.