Beta-lactam Allergy

About this Tool

This algorithm can be used to achieve one of two goals:
1. To select a non-cross reacting beta-lactam and/or
2. To delabel (remove) the allergy using strategies like Direct Challenge or Skin Testing, if indicated

When delabeling strategies are being considered (e.g. Skin Testing or Direct Challenge), the pathway will provide practical guidance on these procedures

  • serious allergy to more than 2 unrelated beta-lactams

  • patient refuses a beta-lactam despite education

  • questions cannot be answered with a reasonable degree of certainty

Pregnancy does not alter the likelihood of reacting or cross-reacting to a beta-lactam

Most experts agree that pregnant patients should NOT be treated differently, especially when:

  • selecting non-cross reacting alternatives

  • in cases of intolerance

  • in cases of delayed reactions

Most clinicians use caution in Type I immediate reactions when considering the offending agent, and are generally uncomfortable challenging pregnant patients without testing

Ideally, if skin testing is indicated, this should be performed by an allergist or someone with experience

Evidence regarding Direct Challenges in pregnancy is lacking; most agree that it can be done in patients with low risk histories

Use the algorithm for any applicable specific guidance in pregnant patients

While most experts agree that the information in this pathway can be applied to kids, particularly the cross-reactivity assessment, detailed guidance pertaining to allergy management and delabeling in pediatrics will be updated upon completion of the allergy initiative led by Dr. Jennifer Balfour

Beta-lactam Allergy Information

~20% of patients at Island Health hospitals have a beta-lactam allergy on their profile

16% are allergic to penicillin, 2.5% are allergic to cephalosporins, and a small fraction are allergic to multiple beta-lactams

Half of all allergy records lack any information about the reaction

The most commonly reported reaction to beta-lactams is "rash", which is often does not help management

Patients labelled "allergic" are more likely to:

  • receive sub-optimal antibiotics

  • suffer from antibiotic-related toxicity (e.g. renal failure)

  • have a longer lenght of hospital stay

  • acquire C. difficile infection, MRSA and VRE

  • <5% of penicillin allergic patients actually experience clinically important reactions

  • Anaphylaxis from penicillin is estimated to be <1 in a million prescriptions

  • IgE antibiodies wane; 10 yrs after the initial reaction 80% of patients lose their IgE-mediated hypersensitivity

  • Most "rashes" are not immediate, Type-I hypersensitivities, but rather benign, delayed reactions

  • Cephalosporin cross-sensitivity is ~2%, and solely dependent on avoidable side-chain similarities

VIHA Allergy Record in Cerner

A detailed allergy window pops-up when the "Allergies" field (located at the top right of the patient's record) is clicked

Change the "Display" field from "Active" to "All" using the drop-down menu to see which allergies have been deleted or modified

A red strike-though bar means that the allergy has been deleted at some point

If a "paper clip" icon appears under Comments, it means that notes have been entered regarding the reaction. Double-click the icon to read the notes, which may include information about the details of the reaction, demonstrated tolerably to other agents, or delabeling information

Strategies to Delabel a Beta-lactam Allergy

Nearly 30% of beta-lactam "allergies" can be clarified to be side effects (e.g. nausea), patient preferences, or identified as entered in error. An average allergy assessment interview lasts ~ 2 minutes

Consists of giving the full dose of the implicated drug in an observed setting to rule out immediate hypersensitivity in lower risk patients. Challenges are usually done with oral drugs (e.g. amoxicillin), but can be carried out with IV antibiotics.

Consists of giving 1/10th of the intended dose, followed by the full dose in an observed setting, to rule out immediate hypersensitivity in lower risk patients. Graded challenges are usually done with oral drugs (e.g. amoxicillin), but can be carried out with IV antibiotics.

NOTE Graded challenges have not been shown to increase safety as most people who react (usually mildly), do so at the final step of the challenge.

Used to investigate immediate hypersensitivity to antibiotics in the penicillin family (e.g. penicillin, ampicillin) in patients with higher risk histories

Skin testing, if negative, is followed by a single dose of amoxicillin, and together this strategy is excellent at ruling out immediate hypersensitivity

Cephalexin is very similar to ampicillin, and skin testing has been sometimes employed, although it has not been robustly validated

Skin testing is not validated with other beta-lactams

More About Allergy Types

Mediated by IgE antibodies
Onset usually within 1 hour (up to 24h)
Cross-reactivity information useful
Skin Testing useful

Mediated by IgG or IgM antibodies
Onset usually >72 hours (up to 14 days)
Reaction is drug specific
Cross-reactivity information is not useful
Offending drug is contraindicated

Mediated by antigen-antibody complexes
Onset usually >72 hours (up to 14 days)
Cross-reactivity information is lacking
If severe (e.g. AIN), all beta-lactams are considered contraindicated unless guided by an expert

Mediated by T-cells
Onset usually >72 hours (up to 3-4 weeks)
Cross-sensitivity is possible but not predictable by skin testing or oral challenge
If severe (e.g. SJS), all beta-lactams are considered contraindicated unless guided by an expert