Can a patient with a history of rash due to penicillin (penicillin) take cefuroxime (cefuroxime) for cellulitis?

Use of Cefuroxime in Patients with Penicillin Allergy and Cellulitis

Patients with a history of rash due to penicillin can safely take cefuroxime for cellulitis due to its low risk of cross-reactivity with penicillin. 1

Understanding Cross-Reactivity Between Penicillins and Cephalosporins

• The previously cited rate of cross-sensitivity between penicillins and cephalosporins (approximately 10%) is now considered an overestimate, based on outdated data from the 1960s and 1970s 1
• Cross-reactivity is primarily determined by the chemical structure of the antibiotic, particularly the R1 side chains 1
• Second-generation cephalosporins like cefuroxime have distinct chemical structures from penicillins, making cross-reactivity negligible 1
• The degree of cross-reactivity is higher with first-generation cephalosporins but minimal with second and third-generation cephalosporins 1

Risk Assessment for Cefuroxime in Penicillin-Allergic Patients

• Cefuroxime is specifically identified as "highly unlikely to be associated with cross-reactivity with penicillin allergy" due to its distinct chemical structure 1
• A meta-analysis showed that the risk of cross-reactivity with second-generation cephalosporins like cefuroxime is minimal (odds ratio 1.1; confidence interval 0.6-2.1) 2
• The Joint Task Force on Practice Parameters (American Academy of Allergy, Asthma and Immunology) states that cephalosporin treatment in patients with penicillin allergy history (excluding severe reactions) shows a reaction rate of only 0.1% 1

Clinical Decision-Making Algorithm

1. Assess the penicillin reaction history:

   • If the patient had only a rash (non-anaphylactic reaction) to penicillin, cefuroxime can be safely administered 1
   • If the patient had anaphylaxis, angioedema, hypotension, or other severe IgE-mediated reactions to penicillin, consider alternative antibiotics or consult an allergist 1

2. Consider the specific cephalosporin:

   • Cefuroxime is a second-generation cephalosporin with a different R1 side chain than penicillin, making cross-reactivity extremely rare 1, 3
   • Table XII in the 2022 drug allergy practice parameter update shows that cefuroxime has a different R1 side chain than penicillins 1

3. Administration approach:

   • For patients with non-severe penicillin allergy history (like rash), cefuroxime can be administered directly 1
   • For patients with severe penicillin allergy history, consider alternative antibiotics for cellulitis or consult with an allergist 1

Important Caveats and Pitfalls

• The risk of cross-reactivity is not zero, and while extremely low with cefuroxime, clinicians should still be prepared to manage potential allergic reactions 1
• Patients with multiple drug allergies may have a higher risk of reactions and might benefit from more cautious approaches 1
• Documentation of the successful administration of cefuroxime should be clearly noted in the patient's medical record to prevent unnecessary avoidance of this medication in the future 1
• The reaction rate to cefuroxime among patients with a confirmed penicillin allergy was found to be just 0.8% (95% CI: 0.13%-4.1%) 1

Special Considerations

• A study specifically examining patients allergic to penicillins found that they could safely receive cefuroxime despite their penicillin allergy 4
• For patients with cellulitis requiring antibiotic treatment, avoiding appropriate beta-lactam antibiotics unnecessarily can lead to use of broader-spectrum antibiotics that increase risk of antimicrobial resistance 5
• Cefuroxime has been specifically identified as one of the cephalosporins that "do not increase risk of an allergic reaction" in penicillin-allergic patients 3