Beta-lactam allergy: Benefits of de-labeling can be achieved safely

Far too many patients carry an inaccurate label of beta-lactam allergy and consequently receive alternative antibiotics, often with too broad a spectrum, a higher risk of adverse events, an increased chance of selecting for resistance, and greater cost. Ten percent of patients are labeled with a penicillin allergy and 2% with a cephalosporin allergy. Yet, among patients with a reported penicillin allergy, only 5% to 8% of adults and 2% of children have a positive penicillin skin test.[1-3] This disconnect may result from a poor understanding of allergy by patients and a lack of useful assessment tools in many primary care settings. An episode of gastrointestinal intolerance can be reported as an allergy. A viral rash that shows up after initiation of antibiotics may be mislabeled as an allergy. Some assume that antibiotic allergies are familial and label a relative. Even when the initial label is accurate, we often fail to acknowledge that the risk of repeat IgE-mediated hypersensitivity to similar drugs diminishes with time, falling 80% over 10 years.[4]

In dentistry, substitution to clindamycin makes up 13% of all prescriptions in BC, significantly increasing the risk for adverse events such as C. difficile infection. Efforts should be made to investigate the nature of the allergy and determine if patients can safely receive a beta-lactam, even in the setting of a well-documented prior reaction. Avoiding unnecessary substitutions or staying within the beta-lactam class, when safe, can bring both clinical and public health benefits.  

Traditional teaching attributes beta-lactam allergy to the commonality of the beta-lactam ring implying broad cross-reactivity between beta-lactams. This probably applies mostly to penicillins but not cephalosporins. Recently, it has been recognized that cross-reactivity is predominantly due to side chain similarity when it comes to cephalosporins. Those with only minor and delayed allergic symptoms such as a rash do not have an absolute contraindication to beta lactam use and can be safely retreated using guidance around cross reactivity. Figure 1 is a chart from the Interior Health Authority that illustrates when this risk is present or absent. Keeping a graphic like this as an office wall chart can aid decisions on subsequent antibiotic therapy. Many people with minor reactions who receive the same agent years later do not have a repeat reaction.

The goal of an allergy assessment strategy is to allow use of the most optimal antibiotic and make sure that any ongoing documentation of allergy is accurate. An effective assessment should employ a short, logical series of questions possibly aided by a flowchart (e.g., Figure 2). What were the symptoms that led to the diagnosis of allergy? How soon after first receiving the drug were they experienced? Was there severe wheezing or swelling of the mouth or throat consistent with anaphylaxis? Were there any very severe manifestations such as Stevens-Johnson syndrome or interstitial nephritis, and did the reaction take your patient to an ICU?

Following such questions, patients who merely had GI intolerance, an unpleasant taste in the mouth, a headache, or other nonallergic symptoms might have their allergy label removed. This can be documented on their chart, by handing them information, and ideally should prompt a revision to the Pharmacare record. The BC Provincial Antimicrobial Clinical Experts are developing a standardized practice guideline and tools for hospital stewardship programs for de-labeling beta-lactam allergies.

Anaphylaxis history rightly deserves more caution and can benefit from further assessment by an allergist, but cross-reactions to agents with a different R1 side chain are rare. Some more severe reactions such as Stevens-Johnson syndrome, interstitial nephritis, and hemolytic anemia [Figure 1] represent an ongoing contraindication to beta-lactam use.

All professions involved in prescribing and administering antibiotics play a role in accurate labeling of allergies. We need to engage pharmacists, dentists, nurses, and others in the effort. Allergy specialists do not have the capacity to evaluate every case, but consultation may be wise if there is a history of anaphylaxis or other severe outcome or a high likelihood of needing to treat with an agent to which there has been a true allergic reaction. If we focus on accurately charting beta-lactam allergy status, we can increase the efficacy and safety of treatment while decreasing costs and risk.
—David M. Patrick, MD, MHSc, FRCPC
BCCDC
University of British Columbia, School of Population and Public Health
—Abdullah Al Mamun, MBBS, MPH
BCCDC
—Nick Smith, MPH
BCCDC
—Emily Rempel, PhD
BCCDC
—Piera Calissi, PharmD
Interior Health Authority
—Edith Blondel-Hill, MD, FRCPC
Interior Health Authority

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.

References

1.    Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: An updated practice parameter. Ann Allergy Asthma Immunol 2010;105:259-273.

2.    Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract 2013;1:258-263.

3.    Abrams EM, Atkinson AR, Wong T, Ben-Shoshan M. The importance of delabeling β-lactam allergy in children. J Pediatr 2019;204:291-297.

4.    Blanca M, Torres MJ, Garcia JJ, et al. Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol 1999;103:918-924.