Nearly 10% of Americans report being allergic to penicillin, but fewer than 5% are confirmed with formal testing. “This is a large number of patients who might otherwise receive an inferior or higher-risk treatment unnecessarily,” says Nicholas A. Turner, MD, MHSc. “As a result, these patients are at higher risk of poor outcomes from their infection or from receiving secondary or alternative antibiotic choices like fluoroquinolones, which are often chosen for those with penicillin allergy but carry higher risks for Clostridioides difficile infection (CDI).”

For a study published in JAMA Open Network, Dr. Turner and colleagues evaluated a comprehensive, pharmacist-led allergy assessment program that was launched in two phases. First, they evaluated structured allergy histories and skin testing as a part of antibiotic stewardship efforts at the hospital level. Next, they incorporated individual risks of CDI and mortality. “We first wanted to expand access to penicillin allergy assessments, but we also tested for important outcomes of interest to both individual patients and hospitals,” explains Dr. Turner. “Our goal was to have a unique dual analysis with hospital- and individual-level analyses.”

The longitudinal analysis looked at hospital-level outcomes during three periods, the first of which was at 15 months before the intervention started. In phase 1, a structured allergy history was examined at 16 months. In phase 2, a comprehensive assessment that included penicillin skin testing was completed at 52 months. The researchers then looked at hospital-level outcomes, which included antibiotic days of therapy and hospital-acquired CDI incidence. Individual outcomes, including antibiotic selection, overall survival, and CDI-free survival, were also assessed.

Improving Antibiotic Selection

In the longitudinal analysis, the study found that allergy assessments and penicillin skin testing were temporally associated with less use of high CDI-risk antibiotics, and penicillin skin testing was associated with a lower incidence of hospital-acquired CDI. In an embedded propensity-matched case-control analysis, penicillin skin testing was also correlated with less receipt of high CDI-risk antibiotics. Patients assessed by pharmacists for penicillin allergy had better overall and hospital-acquired CDI-free survival rates than those who were unassessed (Figure).

“Our findings suggest that engaging pharmacists in allergy de-labeling is a safe and effective force multiplier for improving antibiotic selection,” says Dr. Turner. “What benefits patients also appears to benefit hospitals that treat them. For patients, survival was better and CDI risk was lower for those who were assessed. From the hospital perspective, rates of CDI decreased. Importantly, even if a site was unable to perform full penicillin skin testing, there appeared to be incremental benefit in simply having site pharmacists conduct allergy assessments using history alone.”

The Impacts of Allergy De-Labeling

Dr. Turner says there were two keys to success of the intervention. “First, we supported pharmacists to operate at the top of their scope of practice,” he says. “This helped us to reach a much larger patient population in need. Second, many pharmacists serve key roles in antibiotic stewardship. This is a powerful combination to help teams select the best treatment course for patients while also being able to intervene when reported allergies would otherwise limit those choices.”

The unique pharmacist-led protocol has the potential to expand access to de-labeling opportunities while also being integrated within an existing antibiotic stewardship infrastructure. “Penicillin allergy de-labeling is an important service for hospitals to offer,” says Dr. Turner. “With the help of trained pharmacists, we can expand access while improving objective quality measures. We hope these data prompt hospital administrators to think about how they might leverage their pharmacy staff to expand access to this service.”

The study team is collecting data on a next phase for their study. “For many of our study subjects, the initial antibiotic receipt doesn’t tell the whole story,” Dr. Turner says. “They might receive these agents again in the future. Our next phase will aim to capture these longer-term outcomes and measure their influence on later outpatient antibiotic receipt. It’s possible the impact of allergy de-labelling can continue to accrue even more benefits over time.”

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