Antibiotic Use in Patients with Penicillin Allergy

Introduction to Cross-Reactivity

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, 2

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

Side chain similarity is the primary determinant of cross-reactivity risk between penicillins and cephalosporins 3, 4
Cross-reactivity rates vary significantly based on side chain similarity:
Aminocephalosporins with shared R1 side chains should be avoided in penicillin-allergic patients 3

Cefazolin has a unique side chain and very low cross-reactivity (0.7-0.8%) with penicillins despite being a first-generation cephalosporin 3, 1
Third and fourth-generation cephalosporins with dissimilar side chains (ceftriaxone, ceftazidime, cefepime) have much lower cross-reactivity (2.11%) 3
Patients with suspected immediate-type penicillin allergy can receive any carbapenem without prior allergy testing 1, 5
The risk of cross-reactivity between penicillins and carbapenems is only 0.87% 5
Aztreonam can be safely administered to patients with penicillin allergy, except for those allergic to ceftazidime and cefiderocol due to shared side chains 1, 6

For immediate-type penicillin allergies, avoid all penicillins and cephalosporins with similar side chains, and consider cefazolin, third/fourth-generation cephalosporins with dissimilar side chains, carbapenems, or aztreonam as safer alternatives 1, 3, 4, 5
For delayed-type penicillin allergies, avoid all penicillins if reaction occurred within 1 year, and avoid cephalosporins with similar side chains as the culprit penicillin, but carbapenems and aztreonam can be used without special precautions 1, 6