β-lactam allergy
From IDWiki
Hypersensitivity Reactions
- Type I (IgE-mediated)
- Anaphylaxis
- Itchy rash
- Penicillins should be avoided
- Type II (IgG-mediated)
- Non-itchy rash
- Rash will improve if treatment continues, no need to avoid penicillins
- Type IV (cell-mediated)
- Toxic epidermal necrolysis
- Stevens-Johnson syndrome
- Penicillins should be avoided
Cross-Reactivity
- The following applies to immediate, IgE-mediated hypersensitivity reactions
- Cross-reactivity within penicillins is mediated by homology of the R1 side chain (referring to the C6 side chain) and by the β-lactam ring itself
- Cross-reactivity between penicillins and cephalosporins is mediated by homology of the R1 side chains (referring to the C6 side chain in penicillins or the C7 side chain in cephalosporins)
- Cross-reactivity within cephalosporins is mediated both by homology of the R1 side chains and also R2 side chains (referring to the C3 side chain)
- There is very low (~2%) cross-reactivity between penicillin allergy and carbapenems1
| Antibiotic | R1 | R2 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| G1 | G2 | G3 | G1 | G2 | G3 | G4 | G5 | G6 | G7 | |
| Penicillins | ||||||||||
| Penicillin | X | |||||||||
| Ampicillin | X | |||||||||
| Amoxicillin | X | |||||||||
| First-Generation Cephalosporins | ||||||||||
| Cefazolin | ||||||||||
| Cephalexin | X | X | ||||||||
| Cefadroxil | X | X | ||||||||
| Cephalothin | X | X | ||||||||
| Second-Generation Cephalosporins | ||||||||||
| Cefotetan | X | |||||||||
| Cefoxitin | X | X | ||||||||
| Cefuroxime | X | |||||||||
| Cefaclor | X | |||||||||
| Third-Generation Cephalosporins | ||||||||||
| Cefotaxime | X | X | ||||||||
| Ceftriaxone | X | |||||||||
| Ceftazidime | X | |||||||||
| Cefixime | X | |||||||||
| Cefdinir | ||||||||||
| Fourth-Generation Cephalosporins and Higher | ||||||||||
| Cefipime | X | |||||||||
| Ceftaroline | ||||||||||
R1 Side Chains (C6 and C7)
- Group 1: penicillin, cephalothin, cefoxitin; similar to ticarcillin
- Group 2: amoxicillin, ampicillin, cefaclor, cephalexin, cefadroxil; similar to penicillin piperacillin
- Group 3: cefipime, cefotaxime, ceftriaxone; similar to ceftazidime and aztreonam
- Ceftazidime and aztreonam; similar to group 3
R2 Side Chains (C3)
- Group 1: cefadroxil, cephalexin
- Group 2: cefotetan
- Group 3: cefotaxime, cephalothin
- Group 4
- Group 5: cefuroxime, cefoxitin
- Group 6: cefixime
- Group 7: ceftazidime
Management
Penicillin Allergy
- Consider skin testing
| Class | Cross-reactivity | Notes |
|---|---|---|
| Cephalosporin, 1st generation | 2-8% | Based on poor studies. Avoid cephalexin and cefaclor in ampicillin allergy. |
| Cephalosporin, 2nd generation | 2% | Avoid cefoxitin in penicillin allergy. Avoid cefadroxil and cefprozil in amoxicillin allergy. |
| Cephalosporin, 3rd generation | <1% | Generally considered safe. |
| Cephalosporin, higher generation | N/A | No data available, but generally considered safe. |
| Carbapenem | 1% | Generally considered safe. |
| Monobactam | <1% | Avoid aztreonam in ceftazidime allergy. |
Massachusetts General Hospital Algorithm (2019)
- Developed at MGH2
Mild Reaction
- Includes minor rash (not hives), maculopapular rash (mild type 4 reaction), allergy that is listed but denied by the patient, or an unknown reaction without mucosal involvement, skin desquamation, organ involvement, or need for medical evaluation
- Okay to use cephalosporins and carbapenems
- Can use penicillin by test dose procedure
Type 1 Reaction
- Includes anaphylaxis, angioedema, wheezing, laryngeal edema, hypotension, hives, and urticaria
- Also use for unknown reaction without further details
- Okay to use 3rd generation or higher cephalosporin by a test dose procedure
- Alternatively, can use aztreonam or carbapenems
- Alternatively, can get skin testing if a penicillin or early-generation cephalosporin is preferred
Type 2, 3, or 4 Reaction
- Includes serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute interstitial nephritis, drug reaction with eosinophilia and systemic symptoms, hemolytic anemia, and drug fever
- Avoid all penicillins, cephalosporins, and carbapenems
Further Reading
- Cross-reactivity in β-Lactam Allergy. J Allergy Clin Immunol Pract. 2018;6(1):72-81.e1. doi: 10.1016/j.jaip.2017.08.027
- Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses. J Allergy Clin Immunol Pract. 2019;7(8):2722-2738.e5. doi: 10.1016/j.jaip.2019.05.038
References
- ^ Brittany Kula, Gordana Djordjevic, Joan L. Robinson. A Systematic Review: Can One Prescribe Carbapenems to Patients With IgE-Mediated Allergy to Penicillins or Cephalosporins?. Clinical Infectious Diseases. 2014;59(8):1113-1122. doi:10.1093/cid/ciu587.
- ^ Anna R. Wolfson, Emily M. Huebner, Kimberly G. Blumenthal. Acute care beta-lactam allergy pathways: approaches and outcomes. Annals of Allergy, Asthma & Immunology. 2019;123(1):16-34. doi:10.1016/j.anai.2019.04.009.
