What antibiotics are contraindicated in patients with a known allergy to penicillins (beta-lactam antibiotics)?

Antibiotics Contraindicated in Patients with Penicillin Allergy

In patients with penicillin allergy, other penicillins should be avoided, while cephalosporins with similar side chains to the culprit penicillin carry a significant cross-reactivity risk (5-17%) and should be used with caution. 1

Cross-reactivity Patterns by Antibiotic Class

Penicillins

• All other penicillins should be avoided in patients with suspected immediate-type allergy to penicillins that occurred within the past 5 years 1
• For non-severe immediate-type reactions that occurred >5 years ago, other penicillins may be used in a controlled setting with monitoring 1
• For delayed-type allergies that occurred within 1 year, all other penicillins should be avoided 1

Cephalosporins

• Side chain similarity is the primary determinant of cross-reactivity risk between penicillins and cephalosporins 1
• Cross-reactivity rates vary significantly based on side chain similarity:
  • Cephalosporins with identical side chains to penicillins: 16.45% cross-reactivity 1
  • Cephalosporins with intermediate similarity: 5.60% cross-reactivity 1
  • Cephalosporins with low similarity: 2.11% cross-reactivity 1

Specific Cephalosporins to Avoid

• Aminocephalosporins with shared R1 side chains should be avoided in penicillin-allergic patients 1
  • Cephalexin
  • Cefadroxil
  • Cefprozil
  • Cefaclor

Safer Cephalosporin Options

• Cefazolin has a unique side chain and very low cross-reactivity (0.7-0.8%) with penicillins despite being a first-generation cephalosporin 1
• However, the FDA label for cefazolin states it is contraindicated in patients with known allergy to the cephalosporin group of antibiotics 2
• Third and fourth-generation cephalosporins with dissimilar side chains (ceftriaxone, ceftazidime, cefepime) have much lower cross-reactivity (2.11%) 1, 3

Carbapenems

• Patients with suspected immediate-type penicillin allergy can receive any carbapenem without prior allergy testing 1, 4
• The risk of cross-reactivity between penicillins and carbapenems is only 0.87% 4
• However, meropenem's FDA label states it is contraindicated in patients with known hypersensitivity to beta-lactams 5

Monobactams

• Aztreonam can be safely administered to patients with penicillin allergy 1
• Exception: Aztreonam shares an identical side chain with ceftazidime and cefiderocol, so cross-reactivity may occur in patients allergic to these specific cephalosporins 1

Clinical Decision Algorithm

1. For immediate-type penicillin allergies:

   • Avoid all penicillins 1
   • Avoid cephalosporins with similar side chains (cephalexin, cefaclor, cefadroxil) 1
   • Consider cefazolin, third/fourth-generation cephalosporins with dissimilar side chains, carbapenems, or aztreonam as safer alternatives 1, 4

2. For delayed-type penicillin allergies:

   • Avoid all penicillins if reaction occurred within 1 year 1
   • Avoid cephalosporins with similar side chains as the culprit penicillin 1
   • Carbapenems and aztreonam can be used without special precautions 1

Important Considerations

• The risk of cross-reactivity is often overestimated in clinical practice 6
• Both the beta-lactam ring structure and side chains can contribute to cross-reactivity, but side chain similarity is the predominant factor 7
• Patients with urticaria as their allergic manifestation may have higher rates of cross-reactivity with cephalosporins (30.65%) compared to those with other symptoms (8.11%) 7
• First-generation cephalosporins (except cefazolin) have significantly higher cross-reactivity with penicillins (OR = 4.8) compared to second-generation (OR = 1.1) or third-generation cephalosporins (OR = 0.5) 8