β-lactam and more specifically penicillin allergy is the most commonly reported allergy in hospitalised patients. However, 90-95% of these allergy labels are inaccurate. There are several reasons for this. Many patients have intolerances such as nausea which would not usually be a reason to avoid a β-lactam. Many are mis-labelled in childhood – e.g. viral rash that was thought to be antibiotic related. Even patients with a genuine allergy, may lose this allergy over time (80% will resolve after 10 years). The label of penicillin allergy is detrimental to patients and our system. Penicillin allergy is associated with increased risk of C. difficile and MRSA infection. These patients get more expensive, more toxic antibiotics.
A penicillin allergy label should be re-evaluated when possible and removed if appropriate.
Drug allergy: adverse drug reaction that results from a specific immunologic response to a medication.
Anaphylaxis: acute, life-threatening allergic reaction which may involve skin, gastrointestinal, respiratory and cardiovascular symptoms.
Dermatologic reaction: most common adverse drug events (often morbiliform or maculopapular rashes).
Pseudoallergic reaction: idiosyncratic adverse drug reactions with signs and symptoms that mimic immunologic drug allergies, but in which immunologic mechanisms have not been demonstrated.
Adverse reactions: any undesirable, or unintended affect caused by a medication. Often described as a drug allergy, but of non-immunologic etiology. Includes pseudoallergic and “allergic type” reactions and can include itching, nausea, diarrhea, constipation, headache, and hypotension.
| Reaction | Pathophysiology | Onset | Recommendation |
|---|---|---|---|
Non-allergic adverse reactions
|
Idiopathic | Variable | May use a β-lactam antibiotic |
“Allergic type” delayed mild rash
|
Idiopathic | Variable | May use β-lactam antibiotic from a different class |
“Allergic” with immediate hypersensitivity reaction
|
Type I or IgE-mediated | Minutes to hours | Avoid all β-lactam antibiotics Consider Infectious Diseases consult and referral to outpatient Allergist |
Cytotoxic or cytolytic reaction
|
Type II with antibody (usually IgG) mediated cell destruction | Days to weeks High doses |
Avoid all β-lactam antibiotics |
Immune complex-mediated
|
Type III reaction with immune complex deposition and complement activation | 7-21 days after initiation of drug | Avoid all β-lactam antibiotics |
Delayed hypersensitivity reaction
|
Type IV reaction mediated by T cells | Days to weeks Upon re-challenge symptoms usually within 24 hours |
Avoid all β-lactam antibiotics Consider Infectious Diseases consult |
Pseudoallergic reactions
|
Idiosyncratic | Variable, usually within hours | Depends on reaction |
Note: amoxicillin or ampicillin can cause mild delayed skin rashes that are often caused by an interaction between the amino-penicillin and a viral infection (e.g. infectious mononucleosis caused by Epstein-Barr Virus or cytomegalovirus). These are not true allergic reactions and therefore it is not necessary to avoid use of other β-lactam antibiotics.
Penicillins, cephalosporins, and carbapenems are chemically related β-lactam antibiotics with varying potential for cross-reactivity. The cross reactivity of penicillin to cephalosporins is >8% and penicillin to carbapenems is >1%.
| Penicillins | Cephalosporins | Carbapenems |
|---|---|---|
penicillin G penicillin VK amoxicillin ampicillin cloxacillin piperacillin ticarcillin |
ceFAZolin cephalexin cefTRIAXone cefaclor cefepime cefixime cefuroxime cefOXitin cefTAZidime |
ertapenem meropenem imipenem |
Consider ID/Allergist consult if patient would benefit from beta-lactam allergy assessment.
Johansson SG et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113:832.
Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139:683.
Weiss ME and Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy. 1988;18:515.
CMAJ 2019 February 25;191:E231. doi: 10.1503/cmaj.181117