Penicillin allergies are among the most commonly reported drug allergies, with 10-15% of the population reporting one, but the truth is, most people who believe they are allergic to penicillin are not.
Cosby Stone, Jr., M.D., M.P.H.
Assistant Professor of Medicine, Division of Allergy, Pulmonology, and Critical Care Medicine, Vanderbilt University Medical Center
Erroneous penicillin allergy documentation is widespread in healthcare, often based on incomplete histories, childhood reactions that were never confirmed, or side effects like nausea or diarrhea that were mistakenly labeled as allergies. Once recorded in the electronic health record, these labels tend to persist, shaping treatment decisions long after the original event. All of these different pathways to being labeled as allergic to penicillin have led to a major healthcare quality gap: Fewer than 5% of the penicillin allergies currently reported in patient charts turn out to be true allergies when tested, according to research.
The consequences of an inaccurate label
Having a penicillin allergy label changes how doctors treat infections. When penicillin can’t be used, providers often turn to broader or less targeted antibiotics that can be less effective or carry additional risks. Studies show that patients labeled as penicillin-allergic are more likely to receive medications like fluoroquinolones, clindamycin, and vancomycin. These alternatives can increase the risk of serious infections, including Clostridioides difficile (C. diff), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Patients with a penicillin allergy label also tend to have longer hospital stays.
The consequences are especially clear in surgery and serious infections. Surgical site infections account for up to 20%of hospital-acquired infections and are costly and dangerous. Research has shown that patients with a reported penicillin allergy have about a 50% higher risk of developing a surgical infection, often because they cannot receive the most effective preventive antibiotics.
How allergies can be safely evaluated
The good news is that penicillin allergies can be safely evaluated. A careful allergy history — asking what symptoms occurred, how long ago the reaction happened, and whether penicillin has been tolerated since — can clarify risk using validated risk assessments, and is the first step in evaluation. Around 60-70% of patients will report a history that is low-risk for having an ongoing allergy at the time of evaluation. For people with low-risk histories, a supervised oral dose of amoxicillin, called a direct oral challenge, can then safely confirm whether penicillin is truly an ongoing problem. Large clinical trials have shown this approach to be safe, effective, and efficient, with a 1 in 200 chance of a rash as the main risk.
For people with higher-risk histories, penicillin skin testing also remains a reliable and safe option for most patients. Negative skin testing can then be followed by an oral challenge to confirm that an allergy can be removed from the chart. Together, these approaches help remove inaccurate allergy labels. Finally, some patients will have their allergies confirmed, which also provides additional safety by making everyone aware of a true allergy and the plan to manage it.
Accurately identifying which penicillin allergies need to be kept in a patient’s chart versus removed protects patients. It allows doctors to choose the best antibiotics, lowers the risk of complications, and improves overall care. If you or a loved one has a penicillin allergy listed, it may be worth talking with a healthcare provider about whether that label should be reviewed and tested.
