Penicillin Allergy Testing Underused, Could Lead to Cost Savings

Once a patient is labeled as having a penicillin allergy, it is rarely revisited. The label sticks and increases the patient's risk of receiving subsequent suboptimal, alternative antibiotic therapy, even in cases of unconfirmed penicillin allergy.

Yet, in an era of cost cutting and intensified scrutiny on antibiotic stewardship, there is heightened interest in confirmatory allergy testing to "debunk" false penicillin allergies and minimize the use of unnecessary, high-cost, broad-spectrum antibiotics. In 2016, the American Academy of Allergy, Asthma and Immunology (AAAAI) approved a position statement recommending routine penicillin allergy testing in patients with unverified penicillin allergies.

"Penicillin allergy testing is associated with an unrealized potential: this procedure can accurately identify the approximately nine of 10 patients who despite reporting a history of penicillin allergy can receive penicillins safely," the AAAAI said in its position statement. "The AAAAI encourages more widespread and routine performance of penicillin skin testing for patients with a history of allergy to penicillin or another beta lactam (e.g., ampicillin or amoxicillin)…. We are confident that more frequent and routine performance of penicillin allergy testing will be associated with reduced costs of care, enhanced patient safety, and improved outcomes of care."

Several recent reports show that penicillin allergy testing remains underused and questions remain about how and where testing should be performed.

Who Should Be Tested and How
All individuals with an unconfirmed penicillin allergy should have their penicillin allergy evaluated and, if appropriate, tested to confirm current hypersensitivity or tolerance, according to a study published in the November issue of the Annals of Allergy, Asthma & Immunology. An oral challenge with amoxicillin in patients with low-risk penicillin allergy histories is the optimal method to confirm current tolerance.

Despite patients' fear of severe reaction from reexposure, penicillin-associated anaphylaxis is extremely rare. However, there are known risks that come with the avoidance of penicillin due to unconfirmed allergy, including inappropriate prescribing, inferior clinical outcomes, and higher health care expenditures.

At the Kaiser Permanente Southern California in San Diego, California, from Jan. 1, 2017, to March 30, 2018, 519 children and adults with low-risk penicillin-associated reaction histories had a direct 250-mg oral amoxicillin challenge. One patient had an immediate onset positive result and had a delayed onset positive result. Additionally, 291 adults and children with higher-risk histories had skin testing. Only five patients had positive skin test results and an additional five had a short-term, objective oral challenge reaction after negative skin testing results. There were no delayed-onset oral challenge reactions in the group who underwent skin tests first.

The Kaiser results were similar to six other large studies leading authors Eric Macy, M.D., from the Southern California Permanente Medical Group in San Diego, and David Byles, from the Medical College of Wisconsin in Milwaukee to recommend:

• Low-risk individuals (a history of benign rash, gastrointestinal symptoms, headaches) can safely go to a direct oral amoxicillin challenge with a therapeutic dose to confirm current tolerance. The oral challenge typically involves 250 mg for adults, and one hour of observation to confirm acute tolerance, followed by 5 days of at home follow-up to confirm the absence of clinically significant T-cell–mediated delayed-onset hypersensitivity.
• Skin testing to rule out a high risk of having anaphylaxis during a confirmatory oral amoxicillin challenge in patients with high-risk histories (reaction within the last 12 months or any history of shortness of breath). Puncture and intradermal skin testing should only use penicilloyl-polylysine, with at least 5 mm of wheal and flare greater than the wheal to define a positive test result.

The authors add that individuals seen in all health care settings can be evaluated for current penicillin tolerance, including in the hospital, intensive care units, emergency departments, and outpatient clinics, especially for preoperative workup.

Economic Benefit to Confirmatory Allergy Testing
"Delabeling" children through confirmatory allergy testing for previously unconfirmed penicillin allergies changes subsequent prescription behavior and leads to actual health care savings, according to a study published in May in Pediatrics.

Researchers followed up on 100 children with negative results for a penicillin allergy 500-mg oral challenge with amoxicillin given in a pediatric emergency department. One year after the negative test results, primary care providers and/or parents reported 46 antibiotic prescriptions in 36 patients. More than half of these prescriptions (58 percent) were filled with penicillin derivatives. The cost savings of delabeling patients as penicillin allergic was $1,368.13, the cost avoidance was $1,812.00, and the total potential cost savings for the pediatric emergency department within one hospital system population was $192,223, based upon the approximately 6,700 patients per year with a reported penicillin allergy seen in the pediatric emergency department.

Even greater savings and improvements in patient care could have been realized with better communication of label removal and test results to the child's entire care team, but particularly the child's primary care provider.

With the negative test result, the hospital medical record was delabeled. However, families were relied upon to notify the primary care provider about the test results. One year following the negative test result, more than 80 percent of primary care providers were not notified of allergy testing results and over half still had the allergy documented in the chart.

Takeaway: Expanding confirmatory penicillin allergy testing can benefit patient care and generate health system savings.