How do you introduce an antibiotic to someone with a possible allergy?

Approach to Introducing Antibiotics in Patients with Possible Allergy

For patients with a possible antibiotic allergy, a structured risk assessment should be performed first to determine if the antibiotic can be safely administered directly or if formal allergy testing is needed before administration.

Risk Assessment to Determine Allergy Status

• An antibiotic allergy label can be removed without allergy testing when:
  • The culprit drug has been used since the index reaction without allergic symptoms 1
  • The allergy label was based solely on family history or fear of allergy 1
  • Reported symptoms are not compatible with an allergic reaction (e.g., gastrointestinal complaints only, palpitations, blurred vision) 1
  • There was no temporal association between exposure and symptom onset 1
  • The index reaction was not severe, confined to the skin, and occurred in remote childhood 1
  • The patient cannot recall any details of the reported reaction 1

Administration Based on Reaction Type and Timing

For Immediate-Type Reactions (e.g., urticaria, angioedema, anaphylaxis)

• Non-severe reactions >5 years ago:

  • Can receive the culprit β-lactam antibiotic in a controlled setting 1
  • Can receive other β-lactams with dissimilar side chains without prior testing 1

• Non-severe reactions ≤5 years ago OR severe reactions regardless of timing:

  • Formal allergy work-up is recommended before re-exposure 1
  • If formal allergy testing is unavailable and the indication is vital, re-exposure could be considered in a controlled setting with emergency resources available 1

For Delayed-Type Reactions (e.g., maculopapular rash)

• Non-severe reactions >1 year ago:

  • Can receive the culprit β-lactam antibiotic without formal allergy testing 1
  • Can receive other β-lactams with dissimilar side chains 1

• Non-severe reactions ≤1 year ago:

  • Avoid the culprit antibiotic 1
  • Can receive other β-lactams with dissimilar side chains 1

• Severe reactions (e.g., SCAR - Stevens-Johnson syndrome, toxic epidermal necrolysis):

  • Avoid re-exposure to the culprit drug regardless of timing 1
  • In absence of alternatives, discuss in a multidisciplinary team 1

Cross-Reactivity Considerations

• For penicillin allergy:

  • Can safely receive cephalosporins with dissimilar side chains regardless of reaction severity or timing 1
  • Cefazolin specifically can be used as it does not share side chains with available penicillins 1
  • Can receive any monobactam or carbapenem without prior allergy testing 1
  • No cross-reactivity exists between penicillins and nitrofurantoin 2

• For cephalosporin allergy:

  • Avoid other cephalosporins with similar side chains 1
  • Ceftazidime, cefiderocol, and aztreonam share an identical side chain (higher cross-reactivity risk) 1

• For non-β-lactam antibiotics:

  • Avoid re-exposure to the culprit non-β-lactam antibiotic and others within the same class when the index reaction was severe 1
  • For non-severe reactions, the culprit and other antibiotics within the same class can be reintroduced in a controlled setting 1
  • For quinolones with history of generalized urticaria, avoid all quinolones due to potential direct mast cell release mechanism 1

Practical Implementation

• For patients requiring β-lactams despite penicillin allergy:

  • Vancomycin is indicated for penicillin-allergic patients requiring treatment for serious infections caused by susceptible organisms 3
  • The cross-reactivity between penicillins and second/third-generation cephalosporins (excluding cefamandole) is likely no higher than between penicillins and other antibiotic classes 4
  • For serious infections, desensitization therapy should be considered if efficacy of alternative antibiotics is questionable 4

• Controlled setting requirements:

  • Patient must be observed by trained personnel 1
  • Emergency treatment for allergic reactions must be readily available 1
  • Clear documentation of antibiotic tolerance should be communicated to other healthcare providers 1

Common Pitfalls to Avoid

• Most reported antibiotic allergies (approximately 90%) do not represent true allergies but are due to drug intolerance, idiosyncratic reactions, or symptoms of the concurrent infection 5, 6
• Incorrect allergy labels lead to use of less effective or unnecessarily broad-spectrum antibiotics, contributing to antimicrobial resistance 6, 7
• Oral route should not be relied upon in patients with severe illness, nausea, vomiting, gastric dilatation, cardiospasm, or intestinal hypermotility 8
• Lack of standardized skin testing for all antibiotics in critical care settings can lead to inappropriate antibiotic selection 9