Skip to content

Clinical Decision Support to Challenge Penicillin Allergy

In This Article

  • Allergy testing disproves more than 90% of previously documented penicillin allergies
  • Research shows that the vast majority of patients with a documented penicillin allergy receive alternative antibiotics that carry additional risk
  • Massachusetts General Hospital allergists are developing data-driven clinical decision support tools to help health care providers decide when to rechallenge patients with a documented penicillin allergy
  • Thoughtful, detailed allergy documentation is crucial to a patient's future clinical care and the fight against antibiotic resistance

Reported, but unconfirmed, allergies to penicillin can lead to the unnecessary use of broad-spectrum antibiotics and undermine the goals of antimicrobial stewardship. Kimberly G. Blumenthal, MD, MSc, quality and safety officer for allergy at Massachusetts General Hospital, and co-director of the Clinical Epidemiology Program in the Division of Rheumatology, Allergy and Immunology, is working to create tools to help stratify risk and decide which patients should be rechallenged or see an allergist for testing.

"We need to create safe ways to turn the tide on penicillin allergy overdiagnosis," says Dr. Blumenthal.

False Penicillin Allergy: Common and Costly

According to the Centers for Disease Control and Prevention, 10% of all U.S. patients report a penicillin allergy, but only 1% are actually allergic.

Dr. Blumenthal led the first multihospital exploration of the prevalence of penicillin allergies among inpatients. The findings from almost 11,000 patients at 106 hospitals were published in a research letter in JAMA Internal Medicine in 2020 and found that 16% of the sample had a penicillin allergy noted in their medical records, much higher than the general national rate of documented penicillin hypersensitivity, and those patients had 94% higher odds of receiving broad-spectrum alternatives, which increase antimicrobial resistance and the risk of health care-associated infections.

Dr. Blumenthal and coauthors stressed the importance of questioning and confirming documented penicillin allergies before making antibiotic decisions.

Penicillin allergy assessment was recently endorsed by the American Academy of Allergy, Asthma and Immunology; the Infectious Diseases Society of America; and the Society for Healthcare Epidemiology of America. Dr. Blumenthal then expanded her research in other patient populations, including surgical patients (published in the Annals of Allergy, Asthma and Immunology), pregnant women (published in The Journal of Allergy and Clinical Immunology) and people seen by primary care providers.

"It is becoming more and more clear with all of our research that when you have a reported or documented penicillin allergy, it's usually not true," says Dr. Blumenthal. "But there are harms of being labeled allergic."

Barriers to Widespread Penicillin Allergy Testing

The U.S. health care system does not have the resources to administer a penicillin allergy test to everyone with a documented allergy.

"Fewer than half of all hospitals have access to allergists. And not all allergists are doing penicillin allergy testing at the moment," Dr. Blumenthal says, citing data published in Clinical Infectious Diseases. "Many are focusing on other common allergy issues, such as food and environmental allergies."

Furthermore, the test requires multiple reagents, only one of which is approved by the U.S. Food and Drug Administration and commercially available. The other components must be obtained separately, stored properly and mixed in-house, a somewhat complicated and time-consuming process that primary care providers may not be willing to undertake.

Therefore, Dr. Blumenthal's focus has turned to helping health care providers risk stratify which patients should be sent for testing by an allergist, versus those who can be safely considered for rechallenge.

Creating Clinical Decision Support Tools

Using data from patients who have been tested for penicillin allergy, Dr. Blumenthal is developing clinical decision support tools that can predict a person's likelihood of being truly allergic. These tools will take several factors into consideration:

  • Time since the reaction: "Time is a huge factor," Dr. Blumenthal says. "The more time that passes since the reaction, the less likely it is to be confirmed."
  • Severity of the reaction: "Was it something you could have dealt with at home, or did you have to seek medical care?"
  • Symptoms: The models consider all of the variable reactions our patients present with from rash, shortness of breath, swelling, feelings of lightheadedness or low blood pressure

"The physician or pediatrician would go into this tool and answer all of the questions to the best of the ability or the memory of the patient or caregiver. Then the tool will provide a data-driven score that tells us the person's likelihood of actually being allergic," she says.

Based on the score and other factors, such as proximity to emergency care should the patient have a reaction, the health care provider can decide whether to:

  • Attempt direct amoxicillin challenge
  • Refer the patient to an allergist
  • Proceed with the alternative antibiotic

Dr. Blumenthal envisions the tool being integrated into workflows in electronic medical records. She says: "If you enter a prescription for an alternative antibiotic, an alert will pop up and ask whether you are prescribing it because of a documented allergy. If so, it will prompt you to click on the clinical decision support tool and walk through the algorithm."

Her team has had success with a similar implementation strategy for their clinical decision support tools for hospitalized patients, which were initiated at Mass General prior to spreading throughout the Mass General Brigham health system.

She is working with colleagues throughout the country to gather robust, prospectively collected data and test the algorithm in diverse populations. "We've been making incremental changes to make sure that we're not being too cautious or too aggressive," she says. She hopes to have tools available within five years, starting with primary care patients and operative patients.

The Importance of Detailed Allergy Documentation

In the meantime, Dr. Blumenthal encourages health care providers to think very carefully about what they're documenting. The quality of allergy documentation matters very much in a patient's future medical care, and penicillin allergy documentation has public health implications, given increasing antibiotic resistance.

"Allergies accumulate over a patient's lifetime, and the first person to enter them is very important," she says. "Be as thoughtful as possible, as complete as possible, as detailed as possible."

Documentation of an allergy should include:

  • Name of the drug, route, formulation and number of doses taken/administered or days on the medication
  • Why the medication was prescribed
  • Description of the reaction, including all subjective symptoms and objective evidence
  • The extent of the reaction
  • Treatments required to manage the reaction (from simple over-the-counter remedies at home to epinephrine administration and hospitalization)

"Most of the patients who come to us for evaluation actually gained their penicillin allergy label in childhood, often even before age three. Then this label starts to impact care whenever they need antibiotics," Dr. Blumenthal says. "Removal of allergies from medical records is very hard. So we need to ask ourselves: How often is our care less effective or worse for the patient in front of us because we're afraid that the patient has an allergy? Allergists and the tools we are creating are here to offer help in these circumstances."

Learn more about Clinical Epidemiology at Mass General

Visit the Division of Rheumatology, Allergy and Immunology


Three drugs currently in clinical trials could lead to improvements in treatment for IgG4-related disease over the next three to five years.


At the American College of Rheumatology Convergence 2020, Kristin D'Silva, MD, a rheumatology fellow at Massachusetts General Hospital, reported that COVID-19 patients with rheumatic disease are at high risk of mechanical ventilation.