Β-lactam allergy: Difference between revisions
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Β-lactam allergy
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{{DISPLAYTITLE:β-lactam allergy}} |
{{DISPLAYTITLE:β-lactam allergy}} |
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+ | == Background == |
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+ | * The rate of IgE-mediated penicillin allergies is decreasing with time |
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+ | * Most patient reports of penicillin allergy are either unknown or a cutaneous reaction |
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+ | * Patients with listed allergy often receive second-line, less effective, more expensive, or more harmful treatments |
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==Hypersensitivity Reactions== |
==Hypersensitivity Reactions== |
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*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 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]]) |
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*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) |
*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) |
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+ | === Penicillin === |
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*There is very low (~2%) cross-reactivity between penicillin allergy and [[carbapenems]][[CiteRef::kula2014a]] |
*There is very low (~2%) cross-reactivity between penicillin allergy and [[carbapenems]][[CiteRef::kula2014a]] |
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+ | === All β-Lactams === |
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{| class="wikitable" |
{| class="wikitable" |
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! rowspan="2" |Antibiotic |
! rowspan="2" |Antibiotic |
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=== Penicillin Allergy === |
=== Penicillin Allergy === |
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+ | * Many patients with listed penicillin allergy may be penicillin tolerant due to: |
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− | * Consider skin testing |
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+ | ** Benign delayed hypersensitivity rash is the most common reaction |
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+ | ** IgE-mediated penicillin allergy wanes over time (80% are tolerant after a decade) |
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+ | ** Many patients were never allergic |
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+ | * Consider skin testing for patients with history of severe reaction |
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=== Massachusetts General Hospital Algorithm (2019) === |
=== Massachusetts General Hospital Algorithm (2019) === |
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− | * Developed at MGH[[CiteRef::wolfson2019ac]] |
+ | * Developed at MGH[[CiteRef::wolfson2019ac]][[CiteRef::shenoy2019ev]] |
− | ==== |
+ | ==== Allergy History ==== |
+ | |||
+ | * Intolerance: isolated GI upset, chills, headache, or fatigue |
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+ | * Low-risk history: family history, itching, unknown and remote (>10 years ago), allergy on record but patient denies |
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+ | * Moderate-risk: [[anaphylaxis]], [[angioedema]] or swelling, bronchospasm, cough, nasal symptoms, arrhythmia, throat tightness, hypotension, flushing/redness, dyspnea, rash, [[syncope]], wheeze, dizziness/lightheadedness |
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+ | * High-risk history: [[Stevens-Johnson syndrome]], [[serum sickness]], [[thrombocytopenia]], fever, organ injury (liver or kidney), erythema multiforme, dystonia, anemia, acute generalized exanthematous rash with pustules, [[DRESS]] |
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+ | * Also assess age at time of reaction, time of onset relative to dose, any treatments received, and any other β-lactams that have been used in the past |
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+ | * No challenges or testing should be done for patients with a history of penicillin-associated blistering rash, hemolytic anemia, nephritis, [[hepatitis]], fever, or joint pains |
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+ | |||
+ | ==== Low-Risk History ==== |
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− | * 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 |
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* Okay to use [[cephalosporins]] and [[carbapenems]] |
* Okay to use [[cephalosporins]] and [[carbapenems]] |
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+ | * For patients with a low-risk history with cutaneous reaction, IgE-mediated reaction, or hemodynamic instability, do skin testing first |
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− | * Can use penicillin by test dose procedure |
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+ | * Otherwise, can follow test dose procedure by given a single dose of [[amoxicillin]] (250 mg or 500 mg) and observing |
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− | ==== Type 1 Reaction ==== |
+ | ==== Moderate-Risk History (Type 1 Reaction) ==== |
+ | * If penicillin skin testing is available, it is preferred; if not available, can consider proceeding with graded challenge |
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− | * Includes [[anaphylaxis]], [[angioedema]], [[wheezing]], [[laryngeal edema]], [[hypotension]], [[hives]], and [[urticaria]] |
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+ | ** Give one dose of [[amoxicillin]] 25 or 50 mg and observe for 1 hour; then, |
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− | * Also use for unknown reaction without further details |
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+ | ** Given one dose of amoxicillin 250 mg or 500 mg and observe for 1 hour |
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* Okay to use 3rd generation or higher [[cephalosporin]] by a test dose procedure |
* Okay to use 3rd generation or higher [[cephalosporin]] by a test dose procedure |
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* Alternatively, can use [[aztreonam]] or [[carbapenems]] |
* Alternatively, can use [[aztreonam]] or [[carbapenems]] |
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* Alternatively, can get skin testing if a penicillin or early-generation cephalosporin is preferred |
* Alternatively, can get skin testing if a penicillin or early-generation cephalosporin is preferred |
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− | ==== Type 2, 3, or 4 Reaction ==== |
+ | ==== High-Risk History (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]] |
* Includes serum sickness, [[Stevens-Johnson syndrome]], [[toxic epidermal necrolysis]], [[acute interstitial nephritis]], [[drug reaction with eosinophilia and systemic symptoms]], [[hemolytic anemia]], and [[drug fever]] |
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* Avoid all penicillins, cephalosporins, and carbapenems |
* Avoid all penicillins, cephalosporins, and carbapenems |
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+ | |||
+ | === Graded Test Dose Procedure === |
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+ | |||
+ | * 10% of the standard dose is given and they are monitored for an hour |
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+ | * If no reaction is observed in 1 hour, a full dose is given and they are monitored for another hour |
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==Further Reading== |
==Further Reading== |
Latest revision as of 12:47, 19 September 2024
Background
- The rate of IgE-mediated penicillin allergies is decreasing with time
- Most patient reports of penicillin allergy are either unknown or a cutaneous reaction
- Patients with listed allergy often receive second-line, less effective, more expensive, or more harmful treatments
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)
Penicillin
- There is very low (~2%) cross-reactivity between penicillin allergy and carbapenems1
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. |
All β-Lactams
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
- Many patients with listed penicillin allergy may be penicillin tolerant due to:
- Benign delayed hypersensitivity rash is the most common reaction
- IgE-mediated penicillin allergy wanes over time (80% are tolerant after a decade)
- Many patients were never allergic
- Consider skin testing for patients with history of severe reaction
Massachusetts General Hospital Algorithm (2019)
Allergy History
- Intolerance: isolated GI upset, chills, headache, or fatigue
- Low-risk history: family history, itching, unknown and remote (>10 years ago), allergy on record but patient denies
- Moderate-risk: anaphylaxis, angioedema or swelling, bronchospasm, cough, nasal symptoms, arrhythmia, throat tightness, hypotension, flushing/redness, dyspnea, rash, syncope, wheeze, dizziness/lightheadedness
- High-risk history: Stevens-Johnson syndrome, serum sickness, thrombocytopenia, fever, organ injury (liver or kidney), erythema multiforme, dystonia, anemia, acute generalized exanthematous rash with pustules, DRESS
- Also assess age at time of reaction, time of onset relative to dose, any treatments received, and any other β-lactams that have been used in the past
- No challenges or testing should be done for patients with a history of penicillin-associated blistering rash, hemolytic anemia, nephritis, hepatitis, fever, or joint pains
Low-Risk History
- Okay to use cephalosporins and carbapenems
- For patients with a low-risk history with cutaneous reaction, IgE-mediated reaction, or hemodynamic instability, do skin testing first
- Otherwise, can follow test dose procedure by given a single dose of amoxicillin (250 mg or 500 mg) and observing
Moderate-Risk History (Type 1 Reaction)
- If penicillin skin testing is available, it is preferred; if not available, can consider proceeding with graded challenge
- Give one dose of amoxicillin 25 or 50 mg and observe for 1 hour; then,
- Given one dose of amoxicillin 250 mg or 500 mg and observe for 1 hour
- 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
High-Risk History (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
Graded Test Dose Procedure
- 10% of the standard dose is given and they are monitored for an hour
- If no reaction is observed in 1 hour, a full dose is given and they are monitored for another hour
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.
- ^ Erica S. Shenoy, Eric Macy, Theresa Rowe, Kimberly G. Blumenthal. Evaluation and Management of Penicillin Allergy. JAMA. 2019;321(2):188. doi:10.1001/jama.2018.19283.