Can a patient allergic to penicillin (pcn) and ceftriaxone receive cefepime?

Administration of Cefepime in Patients with Penicillin and Ceftriaxone Allergies

Cefepime can be administered to patients with penicillin and ceftriaxone allergies, as the risk of cross-reactivity is low (approximately 2.11%) when using cephalosporins with dissimilar side chains like cefepime. 1

Understanding Cross-Reactivity Risk

The risk of cross-reactivity between penicillins and cephalosporins is much lower than historically believed and depends primarily on the similarity of their R1 side chains:

• Cross-reactivity between penicillins and cephalosporins with dissimilar side chains (including cefepime) is only about 2.11% (95% CI: 0.98-4.46) 1
• The previously cited 10% cross-reactivity rate is now considered an overestimate 1
• Cefepime has a different side chain structure than penicillin and ceftriaxone, reducing the risk of cross-reactivity

Decision Algorithm for Cefepime Administration

Step 1: Assess the nature of previous allergic reactions

• Low risk: Non-severe reactions (mild rash, GI symptoms) occurring >10 years ago
• Moderate risk: Urticaria or pruritic rashes with features suggesting IgE-mediated reactions
• High risk: History of anaphylaxis, positive skin tests, or multiple beta-lactam allergies

Step 2: Determine appropriate approach based on risk

1. For low-risk patients: Direct cefepime challenge may be appropriate
2. For moderate-risk patients: Consider cephalosporin skin testing if available
3. For high-risk patients: Consider alternative non-beta-lactam antibiotics or desensitization

Skin Testing Considerations

If skin testing is deemed necessary for moderate to high-risk patients:

• Cefepime skin testing concentrations 1:
  • Epicutaneous (prick/puncture): 2 mg/mL
  • Intradermal (first step): 2 mg/mL
  • Intradermal (second step): 2 mg/mL
  • Note: For cefepime, 20 mg/mL is irritating and should be avoided

Important Caveats and Precautions

• The FDA label for cefepime states: "Exercise caution if this product is to be given to penicillin-sensitive patients" 2
• Discontinue cefepime immediately if allergic reactions occur and institute appropriate supportive measures 2
• While skin testing is generally not recommended for routine use, it may be advisable for patients with multiple drug allergies due to possible coexisting sensitivities 1
• In rare cases, patients may have sensitivity to the beta-lactam ring structure itself rather than the side chains, which would affect all beta-lactam antibiotics 1

Alternative Options

If cefepime cannot be used due to high-risk allergy history or positive skin testing:

• Aztreonam (monobactam) is generally safe in patients with penicillin and cephalosporin allergies 3
• Fluoroquinolones or carbapenems may be considered based on the infection being treated 3
• Vancomycin is an option for Gram-positive coverage 3

Monitoring During Administration

If administering cefepime to a patient with history of penicillin and ceftriaxone allergies:

• Administer in a monitored setting with resuscitation equipment available
• Monitor vital signs closely during and after administration
• Be prepared to treat allergic reactions promptly if they occur
• Consider a test dose before administering the full therapeutic dose

The evidence strongly supports that cefepime can be safely administered to most patients with penicillin and ceftriaxone allergies, particularly when the previous reactions were not severe or anaphylactic.