Clinically Speaking

Penicillin may not be a new or flashy drug, but it’s still a lifesaver. Anjeli Kalra, MD, and Kirstin Carel, MD, are making sure people don’t avoid it unnecessarily.

Penicillin de-labeling is an effort to remove the penicillin allergy label from the charts of patients that are not, in fact, allergic to the drug. Approximately 90 percent of people who think they are allergic to penicillin don’t have an allergy.

“The implications are significant,” explained Dr. Kalra, Assistant Professor of Medicine-Allergy/Clinical Immunology. “Patients who are avoiding penicillin get more broad-spectrum antibiotics, which leads to risk of infection, increased hospital stays, longer antibiotic courses – and increased costs as a result.”

Penicillin avoidance causes these problems because if a person starts with a broad-spectrum antibiotic, there are limited options for where to go next if the infection persists. This is especially true for people with a higher risk of bacterial infection, such as people with diabetes or those who are frequently hospitalized.  

“It used to be that we would just choose an alternative, but using alternatives sets us up for antibiotic resistance. We can really make a difference in slowing antibiotic resistance if we can reverse this trend of unnecessary penicillin avoidance,” said Dr. Carel, Associate Professor of Clinical Practice, Pediatrics-Allergy/Immunology.

Recognizing that a true penicillin allergy is dangerous, Drs. Kalra and Carel have introduced a specific de-labeling process at University of Colorado Hospital and Children’s Hospital, respectively. Like most good care, it starts with a good clinical history. By listening to the stories of patients and families about their experiences with penicillin and other antibiotics, the doctors can assess and stratify risk. For example, some families want to avoid penicillin because the child has a sibling or other relative with an allergy. When Dr. Carel explains that the allergy is not generally hereditary, most parents are glad to hear the news.

The next step for children at low risk for penicillin allergy is the one-dose challenge, in which they take a dose of amoxicillin and are monitored closely by a nurse for 30 minutes. For all others (adults and higher risk children), the next step is percutaneous (skin prick) testing, followed by intradermal testing (injection) with penicillin derivatives if the skin prick is negative. If the intradermal test is positive, the patient is allergic and it is not necessary to do anything further. The penicillin allergy label remains in place.

This test has a high negative predictive value; if there is no reaction, the patient most likely does not have a penicillin allergy. But like most tests, it’s not 100 percent accurate. That’s why people who test negative move on to the next step in the de-labeling process: the “two-dose challenge.” The patient receives a small dose of the antibiotic in the clinic and is monitored closely for 30 minutes by a nurse who checks vital signs and ensures that the patient is safe. If that goes well, the patient gets a full dose and is monitored for an hour. If the patient has no reaction, a life-threatening allergy to penicillin can be ruled out.

The de-labeling process confirms what many doctors have suspected: many patients erroneously believe they cannot tolerate penicillin. Many adults avoid it because they were told at some point that they were allergic to it, and they often don’t remember what happened or why they were told they are allergic. In many of those cases, there was no actual reaction and the allergy label was a mistake. In other cases, there was a reaction but it was unrelated to the penicillin, or experienced an unpleasant side effect that wasn’t an allergic reaction. In a few cases, there was a true allergic reaction but the person is no longer allergic.

Most of these apply to children as well. According to Dr. Carel, a delayed reaction like a rash is usually not due to the antibiotic but to something else, and it’s not always clear why it happens.

“Parents will often say that their child had a headache or stomachache when they were taking penicillin, and they call it an allergy because that’s the way they know to describe it – a go-to label for any reaction,” said Dr. Carel. “But even when they have a reaction, it may not be due to the penicillin. They may have been taking Augmentin, which has another ingredient that can cause diarrhea. Most children tolerate a penicillin antibiotic like amoxicillin very well.”

Dr. Kalra started working on penicillin de-labeling and University of Colorado Hospital in August 2017. She started working with anesthesiologist Angela Selzer, MD, to do penicillin de-labeling before patients had surgery. She has since formed partnerships across the organization to remove the penicillin allergy label for patients who are not allergic. She is currently working with partners to promote de-labeling in the inpatient setting as well, though limited staff can make it challenging to get to everyone.

“This a great example of putting evidence into practice,” said Jenny Stitt, MD, Assistant Professor of Medicine-Allergy/Clinical Immunology. “Dr. Kalra’s approach is particularly notable for her interdisciplinary collaborations to identify preoperative, transplant and infectious disease patients who would most benefit from de-labeling.”  

For Dr. Carel at Children’s Hospital Colorado, the emergency department is the next area of focus.

“Dr. Carel’s work to reduce the mis-labeling of penicillin allergy is groundbreaking and promises to reduce unnecessary exposure to broad spectrum drugs, reduce excess cost and reduce the risk of multidrug resistant bacteria,” said Daniel Hyman, MD, Chief Medical and Patient Safety Officer at Children's Hospital. “Her leadership of this project has been exceptional and we are looking forward to its application in the ED and then to the community.”

Once they understand the importance of penicillin de-labeling, most physicians are in favor of it. As with most medical practice changes, the challenge is raising awareness about the compelling evidence for de-labeling and helping physicians change their process accordingly. Drs. Kalra and Carel serve as resources for the UCH and CHCO communities to ensure that physicians can give the best possible clinical care for infections while also demonstrating national leadership in the prevention of antibiotic resistance.