Expert Opinion: Why Penicillin Allergy Labels Matter in Hospital Care

Clinical Associate Professor Deanna McDanel shares insights on improving antibiotic stewardship by rethinking penicillin allergy labels in hospital care.

Penicillin allergy is the most commonly reported drug allergy in health care. About one in 10 patients carries this label. Yet research consistently shows that fewer than 5% of these individuals have a true, clinically significant allergy. In hospital settings—where antibiotic use is frequent—this discrepancy has important consequences, according to McDanel.

When patients are labeled as penicillin-allergic, clinicians often turn to broader-spectrum or less effective antibiotics. These alternatives may increase side effects, lengthen hospital stays, raise health-care costs, and contribute to antimicrobial resistance. In some cases, penicillin allergy labels are also associated with higher rates of infections such as MRSA and C. difficile. In short, an inaccurate allergy label can affect not only individual patients, but public health as well.

“Fortunately, penicillin allergy ‘delabeling’ is both possible and safe when done thoughtfully. In hospitals, two primary strategies are used: penicillin skin testing (PST) and direct oral challenge (DOC), and this article summarizes the pros and cons of both approaches,” said McDanel.

With decades of evidence supporting its safety, PST helps identify patients at risk for serious reactions before exposure. It is especially valuable for patients with moderate- or high-risk allergy histories. However, PST requires trained personnel, specialized reagents, and time—resources that are not universally available.

Direct oral challenge, by contrast, involves giving a supervised dose of penicillin to patients identified as low risk based on clinical history and validated tools such as PEN-FAST. Growing evidence shows that DOC is safe and effective in carefully selected inpatients. It is simpler, less resource-intensive, and can be implemented by multidisciplinary teams, including pharmacists and hospitalists.

These approaches should not be viewed as competing strategies, but rather complementary tools guided by risk assessment. Most hospitalized patients with a penicillin allergy label fall into a low-risk category and may be appropriate candidates for DOC. Higher-risk patients benefit from the added safety layer of skin testing.

Expanding routine penicillin allergy evaluation in inpatient care is a critical component of antimicrobial stewardship. By aligning testing strategies with patient risk and institutional resources, health care systems can improve antibiotic prescribing, reduce resistance, and ultimately provide safer, more effective care.