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Most Prior Drug Allergies Can Be Disproved in Older Adults

Key findings

  • This study assessed the characteristics and outcomes of adults ≥65 years old enrolled in a U.S. multicenter prospective cohort who underwent a total of 501 evaluations for patient-reported drug allergies
  • Penicillin allergy evaluations in 296 older adults were safe, with just two participants requiring more than antihistamines for reaction treatment, and effective, with 97% of allergies disproved
  • Prior flushing/facial redness, itching and lip swelling were significantly associated with retention of a penicillin allergy label, whereas penicillin allergy was disproved in all patients ≥80 years old and all men evaluated
  • Of 172 participants evaluated for 205 nonpenicillin drug allergies, all but 10 had allergies disproved
  • Efforts are needed to expand drug allergy delabeling, primarily via referrals of healthy patients from primary care before an urgent need for an antibiotic arises

Medication reconciliation is now standard practice across medicine and a particular focus in older adults, but there's little attention to allergy reconciliation—reassessing drug allergy and delabeling when appropriate. This is true even though drug allergies are known to wane over time, and older patients labeled as having an antibiotic allergy have higher rates of infection, adverse drug events, and Clostridium difficile colitis.

An analysis by the United States Drug Allergy Registry (USDAR) Study Team has highlighted the safety and efficacy of drug allergy evaluation in older patients. John J.O. Accarino, MD, an allergist/immunologist in the Division of Rheumatology, Allergy and Immunology at Massachusetts General Hospital, Kimberly G. Blumenthal, MD, MSc, director of research for the Drug and Vaccine Allergy Center at Mass General and co-director of the Clinical Epidemiology Program in the Division, and colleagues report in Annals of Allergy, Asthma, & Immunology.


USDAR is a longitudinal, prospective cohort of adults who received at least one drug allergy evaluation at five U.S. allergy–immunology clinics. The centers represent different geographic regions and both academic and community practice.

The current analysis included 406 participants enrolled between January 16, 2019, and February 28, 2022, who were ≥65 years old and collectively underwent 501 drug allergy evaluations.

Penicillin Allergy Evaluations

  • 286 (97%) had their allergies disproved.
  • Four of the 10 participants who retained their penicillin allergy label had positive skin tests; only two of the six others required more than antihistamine treatment for drug reactions.
  • Prior flushing/facial redness (P=0.004), itching (P<0.001), and lip swelling (P=0.002) were significantly associated with a retained penicillin allergy label.
  • Allergies were disproved in all 26 patients ≥80 years old and all 80 older men evaluated.
  • Patient-reported onset of symptoms after penicillin exposure and previous need for emergency department evaluation or hospitalization did not influence whether a penicillin allergy label was retained.

Nonpenicillin Allergy Evaluations

172 participants were evaluated for 205 nonpenicillin drug allergies, including 115 allergies to nonpenicillin antibiotics:

  • 10 participants had 12 allergy labels retained.
  • Trimethoprim–sulfamethoxazole was associated with the lowest rate of disproved allergy (5/41 evaluations, 88%); the five participants who retained their allergy label had immediate reactions in the office, and one required intramuscular epinephrine for worsening urticaria.
  • All nine evaluations for tetracycline allergy were negative.

The Need to Expand Drug Allergy Delabeling

In this study, 392 of 411 antibiotic allergies (95%) were disproved.

Drug allergy assessment is an important part of recent emphasis on deprescribing, patient safety, and antibiotic stewardship. Discussion of drug allergy ideally occurs in primary care in advance of an urgent need for an antibiotic.

of adults ages ≥65 had prior antibiotic allergies disproved

of adults ages ≥65 had prior penicillin allergies disproved

of men ages ≥65 had prior penicillin allergies disproved

of adults ages ≥80 had prior penicillin allergies disproved

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Related topics


Kimberly Blumenthal, MD, MSc, of the Division of Rheumatology, Allergy and Immunology, and colleagues found that inpatients with pneumonia who have an allergy to penicillin or cephalosporin recorded in their charts were less likely to receive a guideline-indicated beta-lactam antibiotic than those without it noted.


Researchers at Massachusetts General Hospital analyzed 299,031 safety reports and identified 744 allergy-related safety events they used to create a novel allergy safety event classification schema. With further development, it could be used to reduce patient exposure to known allergens in healthcare settings.