Within the global movement to improve patient safety related to antimicrobial resistance is a focus on the clarification of penicillin allergy and education on when to rechallenge patients.1 According to the Centers for Disease Control and Prevention (CDC), the implementation of an antimicrobial stewardship program (ASP) has helped clinicians improve clinical outcomes and minimize harm with improved antibiotic prescribing.2 The Joint Commission now requires hospitals to establish an ASP and The Centers for Medicare & Medicaid Services (CMS) recently changed the Conditions of Participation to require all hospitals in the United States to implement an ASP in hospitals and long-term care facilities, to ensure that hospitals and long-term care facilities have facility-wide programs.3-5

Although 33 million individuals in the US have a documented penicillin allergy, greater than 95% of these patients can tolerate β-lactam drugs.6 The unnecessary use of alternative antibiotics in patients with penicillin allergies is associated with higher health care costs, increased risk of antibiotic resistance, and suboptimal antibiotic therapy, according to the CDC.7 The evaluation and removal of the penicillin allergy label from the chart of patients without a true allergy will facilitate the use of less expensive medications.6 In 2018, the national annual cost of treating recurrent hospital-acquired Clostridioides difficile infections in the US was estimated at $1.5 billion.8

Rising Drug-Resistant Infections in Connecticut

The purpose of this pilot project was to develop, implement, and evaluate the effectiveness of a penicillin allergy educational program for prescribing providers in Connecticut. Nearly half (49.8%) of Staphylococcus aureus infections in Connecticut are methicillin-resistant (MRSA) compared with a national average of 46.4%. Similarly, 39.7% of Escherichia coli infections in the state are fluoroquinolone-resistant compared with a national average of 34%.9 According to the CDC, Connecticut is 1 of 10 states reported to have a rising number of C difficile infections.10 The heightened rate of resistant pathogen-related hospital-acquired infections and increased emergence of C difficile infections in Connecticut, as compared to national average rates, coupled with the patient population inappropriately labeled to have a penicillin allergy suggests an underlying knowledge gap on the part of providers on antibiotic utilization.

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Educational sessions were used as an initial approach to inform providers on how to appropriately identify and select antibiotics for patients that could lead to increased use of first-line penicillin and a decrease in antibiotic resistance. A literature review searching for penicillin allergy documentation, history, education, as well as penicillin allergy health care costs was conducted. The review identified the need to increase penicillin allergy awareness and education among providers and prescribers. Effectively informing providers in the community about appropriate antibiotic prescribing is one aspect of improving awareness.11


This education pilot program was conducted on 3 medical-surgical units at a 234-bed academic hospital in Farmington, Connecticut, from June 2021 to October 2021. Qualified participants included 42 prescribing providers, including advanced practice nurses, PAs, and physicians. Participants’ identities remained confidential.

Participants were invited via email to complete a knowledge assessment questionnaire before receiving penicillin allergy education. The questionnaire was originally developed by an allergist, infectious disease expert, pharmacist, and internal medicine resident and is constructed of 14 questions and 4 clinical vignettes.12

The education sessions included a PowerPoint presentation demonstrating evidence-based penicillin allergy assessment and delabeling of penicillin allergy. For interactive learning, supplemental educational material comprised of clinical vignettes with patient scenarios and an open forum for questions were included. After the sessions, participants completed posteducational questionnaires.

Outcome Measures and Statistical Analysis

A total of 19 of 42 (45%) prescribing providers completed the initial questionnaire. Two respondents were excluded from the study because they did not participate in the penicillin allergy education program and postquestionnaire. The majority of respondents were advanced practice practitioners (APP) who practice in multidisciplinary critical care and medical-surgical units. Two of the APPs specialized in surgery, 1 was an advanced practice nurse, and 1 was a PA. Three respondents were general medicine attending physicians and 3 were residents. Additional demographic characteristics of the 17 participants are presented in Table 1.

Providers were asked how much time they take to assess medication allergies, whether they review antibiotic allergies on medical records, and how frequently they consult allergy/immunology for an evaluation of antibiotic allergies. The preintervention questionnaire results are listed in Table 2.

In a meta-analysis of 21 studies examining the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients (N=1269), Picard et al found that cross-reactivity varied with the degree of similarity between R1 side chains: 16.5% for aminocephalosporins that share an identical side chain with penicillin; 5.60% for cephalosporins with an intermediate similarity score; and 2.11% for all those with low similarity scores irrespective of cephalosporin generation.13 Eleven observational studies on carbapenem cross-reactivity in penicillin-allergic patients (N=1127) showed a low risk (0.87%) of cross-reactivity to any carbapenem. The study authors concluded that “clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using β-lactams in patients with a suspected or proven penicillin allergy.13 Other researchers have confirmed that first-generation cephalosporin antibiotics have a higher rate of cross-reactivity to penicillin, ranging from 5% to 20%.14-16