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Pharmacy Practice in Focus: Health Systems
Pharmacists improve outcomes by clarifying and delabeling inaccurate antibiotic allergies.
Antibiotic allergies have been reported by approximately 27 million people in the United States.1 However, allergy labeling can negatively affect patient outcomes, including adverse drug reactions (ADRs), antibiotic resistance, higher antibiotic costs (approximately $285 per patient per day), treatment failure, longer hospital lengths of stay, and increased mortality.2,3
When patients present with antibiotic allergies, they are often prescribed the second-line agents for their infection, which may be inferior at the time and/or associated with more treatment failure and infection recurrence.4 Further, antibiotic allergy reporting statistics do not align with actual hypersensitivity reactions; drug hypersensitivity reactions represent 11% of antibiotic ADRs and are reported in approximately 8% of general populations.5,6
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Hypersensitivities to penicillins are reported most frequently at 41.1%, followed by sulfa antibiotics at 12.9% and cephalosporins at 7%.7 Critical allergies are immunologically mediated, with type I (immediate hypersensitivity) reactions occurring rapidly (within an hour of drug administration). Among the reported antibiotic allergies, approximately 10% to 20% are this type.8 Type III (delayed-type) reactions can also occur with antibiotic use, but they may manifest with symptoms of serum sickness and vasculitis between 1 and 14 days of administration. The most common antibiotics associated with these symptoms have been penicillins, cephalosporins, trimethoprim-sulfamethoxazole, and minocycline.9 Type IV (delayed-type) reactions typically involve the skin, with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being the most severe cutaneous reactions that may occur within this type. Antibiotics that can commonly cause SJS or TEN reactions involve tetracyclines, trimethoprimsulfamethoxazole, and dapsone.9
For the past 3 decades, great attention has been taken to preserve antibiotic use and coverage through antibiotic stewardship programs. Much of this focus has been in ensuring that appropriate antibiotics are selected at correct doses and durations for specific infections. However, stewardship of antibiotic allergies must also be integrated to ensure optimal and responsible antibiotic use. Further, the effective implementation of allergy stewardship can occur across multiple pharmacy practice settings.
Over 200 million antibiotics are prescribed and filled in outpatient community pharmacies, with this amount increasing each year. In 2022, 236.4 million antibiotics were prescribed in the outpatient setting.10 In the outpatient pharmacy, it is very important for pharmacists to determine the presence of true allergies with each patient’s report.
Pharmacists can improve antibiotic allergy stewardship by clarifying allergies through allergy assessments of any previously reported reactions with patients upon prescription reception. However, in a review of the antimicrobial dispensing process in community pharmacies, it was found that community pharmacists clarify drug allergies only 54.3% of the time.11 Simple, structured measures could help increase clarifications.
Findings from a study by Song et al demonstrated that a standardized checklist evaluating penicillin allergies used by pharmacists to interview patients was effective for delabeling inaccurate allergies.12 Approximately 24% of patients evaluated were able to have allergies delabeled. The process was efficient, and the interview process took only 5.2 minutes per patient on average.12 The checklist involved in-depth questioning regarding the patient’s family history related to the allergy and the patient’s own allergy, including the reaction during administration of the drug, and what, if any, treatment was required following the reaction and family history of the allergy. Patients had allergies delabeled if reactions described were classified as low risk or an intolerance, which was considered any reaction involving the presence of itching without rash, isolated gastrointestinal upset, headache, or chills. Although the study was completed in the hospital, this practice can be adapted to the outpatient setting due to its streamlined procedures. Through the implementation of more frequent clarification of allergies with patients and their physicians, community pharmacists can make meaningful contributions to antibiotic allergy stewardship. Additionally, pharmacists can provide education to patients on their allergy status and provide them with documentation through pocket cards to prevent confusion and ensure no allergy relabeling in the future. A multidisciplinary approach encompassing patient education, pocket cards, and electronic health record (EHR) notes and alerts has been shown to reduce the incidence of relabeling by 10.4%.13,14
Antibiotic allergies are reported in up to 25% of hospitalized patients, with antibiotic allergy labeling (AAL) associated with reduced adherence to antibiotic guidelines by prescribers.15 Because of this, the use of antibiotics more prone to resistance has increased exponentially.
In 2022, “watch” antimicrobials, which are antimicrobials indicated for limited situations and are targets for resistance, were used over 2 times (45.5 million) more than “access” antimicrobials (22.6 million), defined as antimicrobials with the best therapeutic value and least effect on antimicrobial resistance.16 In findings from a study by du Plessis et al in 2019, only 20% of hospitalized adults had appropriate labeling of an antibiotic allergy through screening, interview, and oral challenging.17
The relatively low frequency of AAL is concerning given that AAL is directly related to appropriate pharmacotherapy and infectious treatment. Patients with labeled antibiotic allergies were shown to be significantly less likely to receive guideline-recommended antibiotic therapy (50% vs 64%; P = .0311) and have higher rates of developing either methicillin-resistant Staphylococcus aureus or Clostridioides difficile (9% vs 4.7%; P = .09) infection compared with those without AAL.18
Stewardship of allergies and antibiotics poses an essential role within the acute care setting. Effective delabeling strategies may include skin testing and test doses performed in patients with reported allergy histories. Skin testing, through skin pricks, can be completed in under 2 hours, and the incidence of ADRs is extremely low (0.1%).19
However, there has been no commercially available skin testing product within the US over the past 20 years. In consideration of this, some hospitals may make their own product in-house, but not all hospitals have the resources to accomplish this. Test doses, a protocol also referred to as limited-step graded challenges, are performed more widely among 85% of US hospitals with no allergy inpatient consultant service.20 This protocol has provided more confidence in allergy delabeling. Among 1046 test doses performed in patients with reported β-lactam allergies, only 3.8% (2.8%-5.2%; P < .05) resulted in a confirmed hypersensitivity reaction.21
Pharmacists within the hospital setting can further progress antibiotic allergy stewardship by highlighting and communicating true allergies to the patient and making them aware of their allergy status. Moreover, pharmacists can make the patient’s community pharmacy aware of the change and document the change in the patient’s EHR within the hospital system. These acts during transitions of care will aid in the improvement of patient outcomes.
Stewardship of antibiotic allergies is also important within long-term care facilities. Documented antibiotic allergies within this setting stand at 39.1%, with penicillins, sulfonamides, and cephalosporins being most prevalent.22 Upwards of 80% of older adults in long-term care facilities receive at least 1 course of antibiotics per year, and this population is more likely to experience the untoward effects associated with the use of alternative antibiotics.23
Consultant pharmacists in this setting may be present to monitor patients’ medication regimens, but they can also serve a larger role contributing to allergy delabeling by further clarifying allergies reported by patients. This can be displayed through the implementation of the standardized allergy checklists previously mentioned in relation to outpatient pharmacy practices. Because this process takes only 5.2 minutes on average per patient, it is feasible to achieve with respect to the limited schedules of consultant pharmacists.12 Although consultant pharmacists usually check in with these facilities on a monthly basis, delabeling allergies consistently will assist in patient care to ensure treatment success even in their absence.
Patients who are older, live in long-term care facilities, and have acute altered mentation or dementia have all been found to have increased allergy relabeling rates of approximately 36%.24 To extend efforts to prevent relabeling during transitions of care, when alternating between hospital, long-term care facilities, and/or home, hospitals can provide patients with pocket cards with documentation of the confirmed presence or absence of an antibiotic allergy. Keeping a pocket card with the patient and their records when they are in transition between both the hospital and long-term care facilities will ultimately reduce the recurrence of inaccurate allergy labeling.
Breanna Wright is a class of 2025 PharmD candidate at Auburn University Harrison College of Pharmacy in Alabama.
Marilyn N. Bulloch, PharmD, BCPS, FCCM, SPP, is an associate clinical professor and director of strategic operations at the Auburn University Harrison College of Pharmacy in Alabama.
Antibiotic allergy stewardship must continue to be a priority in the health care community. Although practitioners are presented with patients who believe they have allergies to certain medications, it is up to pharmacists to further investigate the existence of a true allergy. There are many novel practices to explore that have shown success within various settings. Employing continued commitment to allergy delabeling practices will help to improve impacts on patient outcomes in all settings, including decreased mortality, decreased antibiotic resistance, and decreased costs.
The authors have nothing to disclose.
