Getting to the Bottom of a Patient’s Penicillin Allergy Label
Year: 2024
Type: article
Abstract: Herman Joseph Johannesmeyer, PharmD, BCPS INTRODUCTION The beta-lactam antibiotics, including penicillins, cephalosporins, monobactams, and carbapenems, represent a chemically similar class of antibiotics that are frequently recommended as first-line therapies in the treatment of a variety of different infections.1,2 Their designation as first-line treatments are due in large part to their relatively benign side effect profile and high degree of clinical effectiveness. While up to 10% of adults in the United States have a notation of a penicillin allergy within their medical records, it has been estimated that 95% of those patients with a penicillin allergy listed within their medical record are not truly penicillin allergic.3 A fictitious label of a penicillin allergy may lead to unwarranted use of second-line, non-beta lactam antibiotics. Unnecessary use of these second-line therapies may predispose patients to medication-related adverse reactions, Clostridioides difficile infection, subsequent infection with multi–drug-resistant organisms, and generally undermine antimicrobial stewardship efforts.4,5 The American Academy of Allergy, Asthma, and Immunology (AAAAI) has recently released professional guidance that encourages the proactive delabeling of penicillin allergies in patients who are unlikely to truly be penicillin allergic as a mechanism to promote the use of beta-lactam antibiotics when appropriate.6 Nurses and pharmacists alike are well positioned to conduct patient-centric historic and clinical investigations that may facilitate penicillin allergy delabeling. This review seeks to present the clinical phenotypes with which a beta-lactam allergy may present, define the untoward effects that a fictitious penicillin allergy label may confer to a patient, and propose clinical investigational prompts for nurses and other allied health professionals when interacting with a patient that has a penicillin or other beta-lactam allergy in their medical history. Pathophysiology and Penicillin Allergy Presentation The penicillin antibiotics and beta lactams, more broadly, represent some of the most commonly listed allergens in standard clinical use. Penicillin allergies may present in a variety of different ways with widely different levels of clinical harm associated with each of these allergic phenotypes. The most common allergic reaction from penicillins is that of a morbilliform drug eruption (MDE).7 Morbilliform drug eruptions are benign T-cell mediated reactions that occur after multiple days of drug exposure, usually after at least 1 week of treatment. These dermatologic eruptions occasionally arise in the context of an intercurrent viral infection and may not reappear with subsequent administration of the drug after recovery from viral illness.7,8 Morbilliform drug eruptions occur more frequently in pediatric patients and with the administration of the aminopenicillin antibiotics amoxicillin and ampicillin. These eruptions are classically defined by round macules and papules that are mildly pruritic, remain stationary on the skin, and resolve over the course of several days. While unpleasant, these eruptions are considered clinically benign and resolve without sequelae with removal of the offending agent.9 When the causative agent is considered medically necessary, experts advocate that clinicians may “treat through,” or proceed with continued use of the offending medication, despite the development of a benign maculopapular eruption.10 Allergic reactions mediated by Immunoglobulin E (IgE) represent a mutually exclusive physiologic pathway and portend an increased risk of untoward clinical consequences. In those with IgE mediated adverse reactions, histamine release occurs promptly after exposure to the offending allergen and symptoms usually manifest within 1 hour of drug exposure. Symptoms and an IgE mediated allergy include an irregular, raised, and intensely pruritic urticarial rash. A recently validated clinical rule titled the “1-1-1” criterion, defined as positive if a patient experiences urticaria within 1 hour of the first dose of an allergen which then resolves within 1 day, suggests the presence of an IgE mediated allergy.11 This type of reaction may include anaphylactic reactions. Treatment with antihistamines and/or epinephrine in the event of anaphylaxis is required in the treatment of severe IgE mediated reactions. The risk of IgE mediated reactions wanes over time, with most patients losing hypersensitive allergic responses after 10 years since exposure to the allergen.12 In addition to the above, penicillins and the broader beta-lactam class may rarely induce other severe cutaneous T-cell–mediated reactions. These reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, and others. The development of these reactions generally requires hospitalization followed by lifelong avoidance of the offending agent. Clinical Consequences The penicillin and greater beta-lactam antibiotic class represent a group of highly effective and largely safe antibiotics. The persistence of a penicillin allergy label is not a benign clinical development, as it predisposes patients to increased utilization of second-line antibiotics and portends poorer infectious outcomes compared to those patients without a penicillin allergy. In 1 study, surgical infectious outcomes were reported in the perioperative setting based upon whether patients did or did not have a listed penicillin allergy.13 While cefazolin is the usually recommended first-line antibiotic for surgical site infection (SSI) prophylaxis, patients who were noted to have a penicillin allergy received clindamycin as their perioperative antibiotic to a greater extent than those without a listed penicillin allergy (49% versus 3%; P < .001). Additionally, patients with a penicillin allergy experienced SSIs with greater frequency than those without a penicillin allergy label (adjusted odds ratio [OR] 1.51, 95% confidence interval [CI] 1.02-2.22). A penicillin allergy label additionally predisposes patients to poorer infectious long-term outcomes outside of the operative setting.4 In 1 longitudinal study, 20 092 patients with a health system encounter for infectious reasons were followed for up to 12 years. Patients who had a beta-lactam allergy label were more likely to experience subsequent infections with methicillin resistant Staphylococcus aureus (OR 1.44; 95% CI 1.36-1.53) and vancomycin-resistant Enterococcus (OR 1.18; 95% CI 1.05-1.32) than patients who did not have a penicillin allergy label. Suggested Action Upon Encountering a Penicillin Allergy in the Clinic Current national practice guidelines recommend a variety of proactive approaches to investigate and, when appropriate, delabel or remove a patient’s penicillin allergy from their medical history.6 The suggested mechanisms to accomplish this include risk stratification, direct amoxicillin or cephalosporin challenge, and/or allergen skin testing. While the penicillin allergy label is common in clinical practice, a complete detailing of a patient’s allergic response to beta-lactam antibiotics is notably infrequent.14 One study identified that among those patients with a listed penicillin allergy, 39.8% of patients had a specific drug identified as the source of their allergy, with the remaining 60.2% using broader terms such as “penicillins” or “cephalosporins” as the cause of the allergy.15 Furthermore, only 22.7% of patients had documentation of the characteristics of the allergic reaction experienced by the patient. Accordingly, the process of taking a detailed and guided allergic history when encountering a patient with a penicillin or other beta-lactam allergy represents a high-value opportunity for nurses, pharmacists, and all patient-facing clinicians. When interviewing a patient regarding their allergic history, specific questions should be posed to the patient to comprehensively assess whether they have a low, moderate, or high penicillin allergy risk. This line of questioning should probe whether a patient experienced a simple and expected drug side effect, a benign morbilliform drug eruption, a more serious IgE mediated reaction, a severe cutaneous adverse reaction, or something else entirely. A proposed series of questions is included in Table 1. TABLE 1 - Questions for Patients With Penicillin Allergy Label Question Potential Guiding Prompts Clinical Implication What was the name of the specific medication that you had an allergic reaction to? Eg, penicillin VK, amoxicillin, ampicillin, or another specific medication (ie, not a medication class) Allergy to 1 medication does not preclude the use of all beta-lactam antibiotics. Do you recall the date of the allergic reaction? - - If you don’t recall the date, do you remember approximately when this happened? Less than 5 years ago. Between 5 and 10 years ago. Greater than 10 years ago. Greater time since the original allergy decreases allergic risk. What happened when you took this medication? Eg, nausea, nausea and vomiting, itchiness without rash, rash, light headedness, swelling, facial swelling, shortness of breath, made you pass out, anaphylaxis, cannot remember Non-allergic reactions decrease subsequent allergic risk. Benign cutaneous reactions decrease subsequent allergic recurrence. If you had a rash, how long did it take to develop after starting the medication? Less than an hour. Between an hour to a day. Greater than a day. Greater time to symptomatic onset decreases allergic risk. Did you seek medical attention for your allergic symptoms? Did you need epinephrine or diphenhydramine to treat your allergic symptoms? Did you need to be admitted to the hospital because of your allergy? Requirement of epinephrine or diphenhydramine suggests previous anaphylactic reaction. Requirement of hospitalization suggests previous anaphylactic or severe cutaneous adverse reaction. Do you know if you’ve had penicillin-like antibiotics since this original reaction? And if so, did the allergic reaction come back? - Repeated allergic reactions increase the risk for high-risk allergic recurrence. With the requisite historical clinical data, a variety of approaches can be implemented to remove fictitious penicillin allergy labels when appropriate. Current guidelines recommend direct penicillin allergy delabeling in patients with non-allergic reactions to penicillins such as headache, diarrhea, or avoidance of penicillins due to a family history of penicillin allergy.6 Adult patients with a history of benign cutaneous reactions occurring greater than 5 years previously or those with unknown distant reactions from childhood are considered to be at low risk for recurrences of severe allergic reaction. These patients may undergo a single test-dose challenge of amoxicillin with subsequent monitoring for 1 hour. Those with no allergic response during that time may be safely penicillin allergy delabeled. Patients with higher levels of allergic risk may undergo penicillin skin testing followed by an amoxicillin challenge if negative. Additionally, use of certain cephalosporins may be considered dependent upon the degree of chemical similarity to the original offending allergen. Of note, the first-generation cephalosporin cefazolin has a unique chemical side chain that is not shared with any other cephalosporin or penicillin. Accordingly, the use of cefazolin is recommended as a safe therapeutic maneuver even in those patients with a history of recent IgE-mediated hypersensitivity reactions to other beta-lactams. CONCLUSIONS While penicillin allergies are frequently reported in clinical practice, the majority of patients who have a penicillin allergy label in their medical history are not truly penicillin allergic. While the penicillin antibiotics can rarely cause life-threatening hypersensitivity responses, most penicillin allergies represent delayed and benign cutaneous reactions. The penicillin allergy label is associated with increased use of second-line antibiotics and increased infectious complications. The practice of obtaining a complete and specific allergic history in those patients with a penicillin allergy label represents a low-cost, high-yield medical intervention that can be provided by nurses, pharmacists, and other allied health care providers. Patients with low-risk allergic histories may have their penicillin allergy delabeled after a simple single-dose amoxicillin challenge that can be performed in an office-based setting. The antibiotic cefazolin may be used across the spectrum of allergic histories, even in those with recent IgE mediated reactions to other beta-lactams.
Source: Journal of Infusion Nursing
Author: Herman Joseph Johannesmeyer
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4406087984