Is it safe to use cephalosporins (antibiotics) for cellulitis in patients with a history of anaphylaxis to sulfonamides (sulfa) and penicillins (antibiotics)?

From the Guidelines

Cephalosporins can be used for cellulitis in patients with anaphylaxis to both sulfa and penicillins, but caution is warranted due to a low cross-reactivity risk, approximately 2-4.8% as reported in a 2022 study 1. When considering the use of cephalosporins in patients with a history of anaphylaxis to penicillins, it is essential to weigh the benefits against the potential risks. The cross-reactivity between penicillins and cephalosporins is due to similarities in their beta-lactam ring structures, but newer generations of cephalosporins have modified side chains that reduce this risk.

• Key factors to consider include:
  • The severity of the patient's allergic reaction to penicillins
  • The specific type of cephalosporin being considered, with third or fourth-generation options like ceftriaxone (1-2g IV daily) or cefepime (1-2g IV every 12 hours) being safer than first-generation agents
  • The potential for alternative non-beta-lactam antibiotics, such as clindamycin (600-900mg IV every 8 hours or 300-450mg orally every 6-8 hours), doxycycline (100mg orally twice daily), or linezolid (600mg IV/orally every 12 hours)
• For MRSA coverage, vancomycin (15-20mg/kg IV every 8-12 hours) or daptomycin (4mg/kg IV daily) may be considered, as recommended in the 2014 practice guidelines for the diagnosis and management of skin and soft tissue infections 1.
• Treatment duration is typically 5-10 days, depending on clinical response, as outlined in the 2014 guidelines 1.
• If cephalosporins must be used despite penicillin allergy, consultation with an allergist for skin testing or administering the first dose in a monitored setting is recommended, as suggested in the 2022 practice parameter update on drug allergy 1.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEFAZOLIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS 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. CEFAZOLIN IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.

Cephalosporins should be used with caution in patients with a history of anaphylaxis to penicillins due to the risk of cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2.

• There is no direct information about sulfa allergy in the provided drug labels.
• However, considering the potential risk of cross-hypersensitivity, caution should be exercised when using cephalosporins in patients with a history of anaphylaxis to penicillins or other allergies 2.

From the Research

Cephalosporin Use in Patients with Anaphylaxis to Sulfa and Penicillins

• The use of cephalosporins in patients with anaphylaxis to sulfa and penicillins is a topic of debate, with some studies suggesting a low risk of cross-reactivity 3, 4, 5.
• A study published in 2018 found that the risk of anaphylaxis to cephalosporins in patients with penicillin allergy is low, and that later-generation cephalosporins do not have any skin test cross-reactivity with penicillin/amoxicillin 3.
• Another study published in 2012 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.
• A 2019 review of penicillin allergy evaluation and management found that cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, and that the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy 6.
• A retrospective cohort study published in 2006 found that the absolute risk of anaphylaxis after a cephalosporin was less than 0.001%, and that cross-reactivity is not an adequate explanation for the increased risk of allergic-like events after cephalosporin exposure in patients with prior penicillin reactions 5.
• A study published in 2015 found that the administration of cephalosporins for surgical prophylaxis in patients with a known or reported penicillin-allergy appears appropriate and results in a lower adverse event rate than when clindamycin is administered 7.

Key Findings

• The risk of cross-reactivity between penicillins and cephalosporins is low, especially with later-generation cephalosporins 3, 4.
• The use of cephalosporins in patients with penicillin allergy is generally safe, with a low risk of anaphylaxis 3, 4, 5.
• The choice of cephalosporin should be based on the specific patient's allergy history and the suspected or confirmed pathogen 4, 6.
• Patients with a history of anaphylaxis to penicillins should be evaluated on a case-by-case basis to determine the safest course of treatment 6, 5.