Do not delay antibiotics in septic shock
Use the best available alternative immediately; allergy workup happens after stabilization.
Step 1 — characterize the reaction
| Reaction | Mechanism | Approach |
|---|---|---|
| Anaphylaxis, urticaria, angioedema (within 1h) | Type I IgE-mediated | Avoid PCN class. Consider non-cross-reactive cephalosporin (different side chain), aztreonam, or fluoroquinolone. ID consult for desensitization if no alternative. |
| Maculopapular rash (delayed days) | Type IV T-cell | Most can tolerate cephalosporins / carbapenems. Avoid the offending agent. Test-dose protocol for related agents if needed. |
| SJS/TEN, DRESS, AGEP, hemolytic anemia | Severe cutaneous adverse reactions (SCARs) | Avoid all β-lactams. No challenges, no desensitization. |
| GI upset, family history, "remember being told as a child" | Not IgE-mediated | Likely tolerate β-lactams. Consider PEN-FAST and direct oral challenge under supervision. |
Step 2 — risk stratify with PEN-FAST
Score the original reaction:
- P — Penicillin allergy reported (required entry)
- F — Five years or less since reaction (+2)
- A — Anaphylaxis or angioedema (+2)
- S — Severe cutaneous adverse reaction (+2)
- T — Treatment required for the reaction (+1)
0 points: very low risk of true allergy → direct oral challenge often appropriate.
≤2 points: low risk → consider direct challenge with ID/allergy.
≥3 points: moderate-to-high → skin testing or ID consult before re-exposure.
Step 3 — cross-reactivity matters by side chain
Overall β-lactam cross-reactivity is <3% — much lower than the historic 10% figure. What actually matters is R1 side-chain similarity:
- Amoxicillin / ampicillin share R1 with: cefadroxil, cefprozil, cephalexin, cefaclor — avoid these in IgE-mediated amox allergy.
- Penicillin G/V: no significant side-chain overlap with most cephalosporins → ceftriaxone, cefepime, cefazolin generally safe.
- Cephalosporins to carbapenems: <1% cross-reactivity — usually safe.
- Aztreonam: shares side chain only with ceftazidime; otherwise safe across PCN/cephalosporin allergies.
Bottom line
Don't reflexively switch to vancomycin / fluoroquinolone because of a vague "PCN allergy" label. Most are not IgE-mediated. Reassess every admission.
References
- IDMP Empiric Therapy guidelines
- Trubiano JA et al. PEN-FAST clinical decision rule. JAMA Intern Med (2020).
- Blumenthal KG et al. Penicillin allergy. JAMA (2019).