August 2, 2024

By: Toni Shears

At least 10 percent of patients are reported to be allergic to penicillin, amoxicillin, or other drugs in a common class of antibiotics. The vast majority of them are not allergic at all, a new study confirms, and with careful evaluation, the flags for allergies can be safely stricken from their medical records.

“This opens the door to treating patients with the safest and most effective antibiotics we have — and avoids the risks and complications of less effective drugs prescribed instead,” says Greg Eschenauer, PharmD, a Clinical Pharmacist Specialist in infectious diseases. Removing erroneous labels can potentially translate into improved outcomes and lower costs of care for thousands of patients each year. 

Eschenauer collaborated on an initiative to systematically evaluate patients whose medical records carried an alert, or label, for beta-lactam antibiotic allergies. A specially trained team conducted medication reviews and allergy testing with patients referred for consultation. They found that 94% of patients evaluated were not, in fact, allergic.

Of 700 patients evaluated over one year, 654 had one or more allergy labels removed from their records, clarified, or both. Findings were published in Science Direct, Annals of Allergy, Asthma & Immunology (April 2024).

 

Why so many allergy labels? 

Beta-lactams are a broad class of antibiotics that includes penicillin and amoxicillin, as well as cephalosporins and carbapenems.The vast majority of labels for beta-lactam allergies are for reactions to penicillin or amoxicillin. 

There are many reasons why allergy labels may be wrong or unnecessary. Symptoms like diarrhea that signal an intolerance to the drug may be misinterpreted as an allergy. Likewise, a rash might be a symptom of the infection, not an allergic reaction. A childhood response to penicillin and amoxicillin – often the first antibiotics given to children – may look like an allergy, even if it wasn’t. 

And we can grow out of allergies. As many as 80% of patients who do have an allergic reaction to a drug will lose their sensitivity to it over time, but the labels linger on medical charts for years. “Many patients don’t know how or why they were labeled allergic,” Eschenauer notes, “but once they are, the label sticks.”

Once labeled with beta-lactam allergies, “patients are more likely to receive non-beta-lactam antibiotics when they have an infection, putting them at risk of toxicities like kidney injury and diarrhea from Clostridioides difficile infections. And these alternative drugs often just don’t work as well,” says Eschenauer.

 

Safe, Systematic Allergy Assessment

As an infectious disease pharmacist at Michigan Medicine, Eschenauer’s role is to optimize the treatment of infectious diseases. Beta-lactam allergy labels are an obstacle to that goal, because they significantly restrict the arsenal of antimicrobial options available to fight infections. 

To overcome this hurdle, Eschenauer and colleagues wanted to find a model system to safely evaluate and eliminate inaccurate allergy labels. He and allergist Rajan Ravikumar, MD., teamed up with an infectious disease attending physician, nursing leadership, hospitalist, and a project manager for the pilot project. The pilot showed that testing ruled out allergies for 98% of their small patient group. Eschenauer was able to remove allergy labels for 17 more patients based on medication history review alone. 

Based on this successful model, they developed a business plan and persuaded Michigan Medicine to establish the Beta-Lactam Allergy Evaluation Service. The team evaluated allergies with a two-step, risk-stratified approach: 

  1.  They conducted a thorough medication history review with patients. This process ruled out past reactions that weren’t really allergies. It also revealed that patients had taken a beta-lactam drug in the past and tolerated it safely. Based on this review alone, 149 patients had 162 allergy labels removed. 
  2. Nurse practitioners also conducted drug challenges at the bedside, carefully administering the drug linked to the suspected allergy and monitoring the patient's response. 

Penicillin allergies were confirmed with a skin test or ruled out with a skin test with subsequent challenge. Patients assessed as low risk based on their medication history were given a full dose of the drug. In rare cases, high-risk patients with problematic histories were given a 10% dose of a drug and monitored for reactions; if that was tolerated, the remaining 90% was administered. (The 10/90 challenge was generally used for cephalosporin, rather than penicillin allergies.)  

In summary, 98% of the 381 patients who received any type of drug challenge passed with no allergic response. All 114 penicillin skin tests were negative. 

Of the eight patients that failed tests and showed allergic reactions, two were treated with epinephrine. The others experienced more minor symptoms; four were treated for urticaria or itching. 

The study also looked at whether delabeling could reduce the use of aztreonam, an antibiotic that is generally safe to use in patients with beta-lactam allergies but is more expensive and less reliable. By ruling out allergies, the study reduced aztreonam use by 27%, with a 30% reduction in annual costs for the drug. The study also decreased the need for desensitization procedures by 80% compared to the previous year. Desensitization can lengthen the hospital stay and the time it takes to resolve an infection. 

 

Education is Key
An important part of the Beta-Lactam Allergy Evaluation Service approach is education for patients, primary care providers, and pharmacists. After testing, it’s important that all members of the care team understand that the patient is no longer allergic. “Otherwise, the next time they are asked, the patient may say they are allergic to penicillin and the label will return,” says Eschenauer. In the study, a small number of patients (6%) were relabeled as allergic, mostly for no clinical reason. Follow-up education with patients and the care team and medication review by pharmacists can successfully remove the labels again.

Inaccurate or overly broad labeling has consequences. “Too often, when prescribers see a penicillin label on the chart, they will rule out all beta-lactams to be cautious, and that’s not really necessary,” he notes. Michigan Medicine’s clinical pharmacists work to educate care teams about that, too, with publicly posted guidelines for optimal treatment when allergies are present.

 

Delabeling for Better Outcomes, Lower Costs

The vast overreporting of antibiotic allergies has been recognized in the literature, but practitioners may be unaware of this finding. “Our study confirms this finding and helps raise awareness, but the real value in our service is that we are doing something about it. We’re safely identifying those few patients who truly are allergic and safely de-labelling all those who are not.”

Delabeling can have a significant impact. The study found that at Michigan Medicine, 10% to 20% of inpatients are labeled as allergic to beta-lactam antibiotics — more than 90% of them wrongly. With nearly 50,000 inpatient visits a year, that means somewhere between 4,500 and 9,000 mislabeled patients at just this one hospital system could be missing out on the best antibiotic treatments when they need them. And that doesn’t account for outpatients with infections.

“Almost everyone will need an antibiotic at some point in their life, and beta-lactams are best in class. They are often more effective with fewer side effects than the alternatives. They are an option you want to have,” Eschenauer said. “Too often, an allergy label rules them out unnecessarily.”

That could mean delayed recovery, more adverse effects, and longer, more expensive inpatient stays.

“The Beta-Lactam Allergy Evaluation Service is still relatively new, but our results are promising,” says Eschenauer. “Taking systematic steps to safely assess allergies and remove labels can reduce the complications and extra costs associated with these alternate drugs, and improve infection management for thousands of patients annually.”