β-lactam Cross-reactivity Chart
- Avoid all β-lactam antibiotics if documented severe non-lgE-mediated reaction to penicillin:
- interstitial nephritis
- hepatitis
- hemolytic anemia
- serum sickness
- severe cutaneous reactions
- Stevens-Johnson syndrome (SJS)
- toxic epidermal necrolysis (TEN)
- drug rash with eosinophilia & systemic symptoms (DRESS)
- NB: Be aware that some patients may react to other β-lactams not because of cross-reactivity but because of their underlying predisposition to develop allergic reactions to multiple unrelated drugs (multiple drug allergy syndrome). In these patients, use clinical judgement and caution when prescribing any new antimicrobial.
- Amoxicillin–clavulanate – patients who have a true IgE-mediated hypersensitivity to this drug combination may have an allergy to the clavulanate component, but not amoxicillin or other beta-lactam antibiotics. Consider penicillin skin-testing +/- amoxicillin challenge.
- Piperacillin-tazobactam – Similarly, allergic reaction specific to tazobactam is rare but possible. Consider penicillin skin-testing to determine penicillin class sensitivity.
*Unique cephalosporins:
- Cefazolin
- Cefixime
- Ceftolozane-tazobactam
- Ceftobiprole – expected to cross-react with ceftaroline only as identical R1 side chain
Legend:
X Cross-reactive - DO NOT PRESCRIBE
✓ Different structure/side chain – OK to PRESCRIBE
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Cephalosporins* Cross-reactivity between penicillins and cephalosporins and between cephalosporins is based on side chains |
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Penicillins Cross-reactivity between penicillins is based on β-lactam ring +/- side chains |
1st generation |
2nd generation |
3rd generation | 4th generation | Carbapenems | |||||||||||||||
| ß-lactams | Amoxicillin | Ampicillin | Cloxacillin | Penicillin | Piperacillin | Cefadroxil | Cefazolin | Cephalexin | Cefaclor | Cefoxitin | Cefprozil | Cefuroxime | Cefixime | Cefotaxime | Ceftazidime | Ceftriaxone | Cefepime | Ertapenem | Imipenem | Meropenem |
| Amoxicillin | X | X | X | X | X | ✓ | X | X | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Ampicillin | X | X | X | X | X | ✓ | X | X | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cloxacillin | X | X | X | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Penicillin | X | X | X | X | ✓ | ✓ | ✓ | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Piperacillin | X | X | X | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefadroxil | X | X | ✓ | ✓ | ✓ | ✓ | X | X | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefazolin | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cephalexin | X | X | ✓ | ✓ | ✓ | X | ✓ | X | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefaclor | X | X | ✓ | ✓ | ✓ | X | ✓ | X | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefoxitin | ✓ | ✓ | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefprozil | X | X | ✓ | ✓ | ✓ | X | ✓ | X | X | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefuroxime | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | ✓ | ✓ | X | ✓ | X | X | ✓ | ✓ | ✓ | |
| Cefixime | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Cefotaxime | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | ✓ | ✓ | X | X | ✓ | ✓ | ✓ | |
| Ceftazidime | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
| Ceftriaxone | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | ✓ | X | ✓ | X | ✓ | ✓ | ✓ | |
| Cefepime | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | ✓ | X | ✓ | X | ✓ | ✓ | ✓ | |
| Ertapenem | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | X | |
| Imipenem | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | X | |
| Meropenem | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | X | X | |