Things We Do For No Reason: Failing to Question a Penicillin Allergy History

PCN allergy has risen to the level of a public health issue as PCN-allergic patients are often relegated to second-line broad-spectrum antibiotics.⁷ This public health issue is exacerbated when patients with faux or resolved PCN allergy receive the same treatment. Patients labeled as PCN allergic—whether correctly or incorrectly—have poorer outcomes as noted by increased rates of serious infections and tend to have longer hospital stays.^8-10 Treatment-related secondary infections from the use of broad-spectrum antibiotics, such as Clostridiiodes difficile and vancomycin-resistant Enterococcus, are identified more frequently in PCN-allergic patients.⁷ Additionally, pregnant women with PCN allergy, with or without group B streptococcus infections, have higher rates of cesarean sections and longer hospitalizations.¹¹ The misuse and overuse of antibiotics, especially broad-spectrum medications, has led to resistant bacteria that are increasingly difficult to treat.⁷ Treating with the most narrow-spectrum antibiotic whenever possible is critical. Overall, failure to address and assess PCN allergy can result in treatment failures and unnecessary broad-spectrum antibiotic use.

Avoid beta-lactams for patients with a reported allergy who are medically frail (eg, critically ill intensive care unit patients and those unable to communicate) or have a documented allergic reaction to a beta-lactam within five years. An estimated 50% of patients who had a documented true IgE-mediated allergic reaction within five years of a documented true allergic reaction remain allergic to PCN and are at risk for an allergic reaction with reexposure.¹ PCN allergy evaluation with PCN skin testing (PST) and oral challenge in patients who had a reaction within five years have a higher risk of a fatal outcome with an oral challenge despite negative skin testing. PCN allergy evaluation is best handled on a case by case basis in this population.

Obtain a thorough drug allergy history. If the history is not consistent with a personal history of an IgE-mediated reaction to PCN ever or if there is documentation that PCN was administered and tolerated since the reaction (eg, a dental prescription), a PCN or beta-lactam can be given. An exception to this rule are patients with a history of an allergic reaction to both a cephalosporin and a PCN—approach this as two separate allergies. Remove the PCN allergy if it is not consistent with the history of IgE-mediated reaction or the patient subsequently had tolerated a PCN/PCN derivative. Regarding the cephalosporin issue, patients are often allergic to a side chain of the cephalosporin and not to the beta-lactam ring. Patients should avoid the specific cephalosporin unless the history is also not consistent with an IgE-mediated reaction or the patient had subsequently tolerated this medication. An allergy evaluation can be useful to discern next steps for cephalosporin allergy. Once the antibiotic is administered and tolerated, the medical record should be updated as well to prevent future mislabeling.

If the symptoms associated with a reported history of a PCN allergy are unknown or consistent with an IgE-mediated reaction, or the patient has not been exposed to PCN since the allergic reaction, the patient should undergo PST followed by a supervised oral test dose to determine whether the allergy exists or persists. PCN allergy evaluation is a simple two-step process of PST followed by an oral challenge of amoxicillin. The use of PCN allergy testing as described is validated and safe.¹² A negative skin prick and intradermal test have a negative predictive value that approaches 100%.^12,13 Completing the final step—the oral challenge—eliminates concerns for false-negative testing results and patient fears. Additionally, once a patient has had negative skin testing and passed an oral challenge, he/she is not at increased risk of resensitization after PCN/PCN derivative use.¹⁴

Although the test takes one and a half hours on average, the benefits that follow are lifelong. Improving future management by disproving a reported allergy affects an individual patient’s clinical course globally, results in cost savings, and increases the use of narrow-spectrum antimicrobials. It is particularly important to test PCN-allergic patients preemptively who are at high risk of requiring PCN/PCN derivative antibiotics. High-risk patients include, but are not limited to, surgery, transplant, hematology/oncology, and immunosuppressed patients. Inpatients with PCN allergy have higher antibiotic costs—both for medications used during their hospitalization and also for discharge medications.¹⁵ A study by Macy and Contreras compared the cost of skin testing to money saved by shortening hospitalization days for 51,582 patients with PCN allergy.⁷ The cost for testing was $131.37 each (total of $6.7 million). The testing contributed to a $64 million savings for the three-year study period—savings that is 9.5 times larger than the cost of the evaluation.⁸ A smaller study that looked at cost-effectiveness of PST for 50 patients found an overall cost savings of $11,005 due to the antimicrobial choice alone ($297 per patient switched to a beta-lactam antibiotic).¹⁶