Most Canadians are aware of so-called superbugs: bacteria that are increasingly becoming resistant to many antibiotics. But a report late last year from the Council of Canadian Academics (CCA) quantified the cost to all of us. It found that more than 14,000 deaths in 2018 were associated with antimicrobial resistant infections. Of these deaths, 5,400 were directly linked to antimicrobial resistance (AMR) – a term used to describe the ability of a bacteria to adopt mechanisms that stop antibiotics from working against them. This means that drugs that once treated most infections no longer work.
This process occurs naturally through genetic changes, but it is hastened by the inappropriate use of antimicrobial drugs. The classic example of this is when antibiotics (which only treat bacteria) are used to treat viral infections, like the flu.
“The spread of AMR threatens our ability to treat common infections,” says Jerome Leis, an infectious disease physician at Sunnybrook Health Sciences Centre and a researcher in this field.
Even if resistance rates remain stable, the potential impacts are alarming, with the CCA report estimating total deaths attributable to AMR at just under 256,000 by 2050, and a $13 billion per year cost to Canada’s health care system.
What many people, and probably even some doctors, may not appreciate, is how being labelled with a penicillin allergy can contribute to this public health crisis.
If you have previously been told you have a penicillin allergy, chances are you were not truly allergic or you may have outgrown your allergy. You might be carrying a penicillin allergy mislabel. This not only has a negative impact on your own health, it contributes to bacterial resistance and antibiotic ineffectiveness. Here are five things about penicillin allergies that everyone should understand.
1. Most people who think they have a penicillin allergy are not truly allergic.
“Penicillin is the most commonly listed medication when patients report a drug allergy,” says Derek Leong, a clinical pharmacist at Toronto General Hospital.
Approximately one in 10 Canadians will self-report an allergy to penicillin. “This number is higher amongst hospitalized patients, closer to one in five,” says Leis. However, more than 90% of these people are not truly allergic and can safely receive the drug.
Penicillin allergy is over diagnosed. According to Janine McCready, an infectious disease doctor at Michael Garron Hospital, this is partly because intolerances or side effects, such as nausea or diarrhea, are confused with an allergy. These bothersome but not life-threatening symptoms may not even be related to the drug, but are documented as allergies anyway.
Often, penicillin allergies are diagnosed in childhood. Rashes can develop in common childhood viral or bacterial infections. If a child develops a rash, it may be difficult to tease out the cause – was it the infection or the antibiotic used to treat the infection? Penicillin is often blamed as the culprit, and a mislabelled allergy is born.
“If at any time a little kid has a rash with an antibiotic, the vast majority of that is not going to be an allergic reaction, it’s probably due to the infection,” says McCready.
Penicillin allergies are assumed and rarely challenged, and the person carries the label into adulthood.
2. You can lose your penicillin allergy over time.
Even people who have a true allergy to penicillin aren’t necessarily allergic for life. 80 per cent of them will lose their sensitivity to penicillin in 10 years, and 50 per cent in 5 years.
This is because a true penicillin allergy is caused, in part, by IgE – an antibody that is produced by the immune system in response to an allergen. When someone is exposed to penicillin for the first time, IgE antibodies are made in a process called sensitization. Your immune system can overreact to the penicillin molecule, causing what is known as a hypersensitivity reaction. The most severe reaction is anaphylaxis – where inflammation can lead to throat swelling and difficulty breathing. But these reactions are very uncommon with penicillin. Production of IgE antibodies decreases over time with avoidance of penicillin. This means that even if someone was once allergic to penicillin, by avoiding the drug they can lose their allergy. They can then be tested in the future to see whether the allergy is still present.
“There is a culture around allergy – if you were labelled with something, that stayed with you for life. It’s a new phenomenon to think that you may not always be allergic,” says McCready.
3. People with penicillin allergies may react to other antibiotics, but this is rare.
Penicillins belong to the class of drugs known as beta-lactam antibiotics, which are grouped together based on the common chemical structural feature, the beta-lactam ring. People with penicillin allergies are often not prescribed other antibiotics in the beta-lactam family, because of the fear of cross-reactivity. These include cephalosporins, another important group of antibiotics that includes cephalexin (Keflex), ceftriaxone and cefixime.
Cross-reactivity occurs when the chemical structures on one drug are closely related to those on another, and so IgE antibodies are mistakenly produced when the immune system recognizes the related antibiotic.
But the fear of cross reactivity has been overblown, say experts. It is estimated that less than two per cent of people with a penicillin allergy are also allergic to the cephalosporin class of drugs. “The widely-cited rates of 10 per cent cross reactivity are based on old studies,” says McCready. “Even in those with anaphylaxis to penicillin, we can safely give a large number of the cephalosporins.”
4. Your penicillin allergy mislabel might cause you to receive sub optimal medical treatment.
Being labelled with a penicillin allergy greatly limits the number of antibiotics you can be prescribed. “Reported allergy to penicillin leads to the use of alternative antibiotic therapies, which may be higher in cost and requires more monitoring,” says Leong.
People with a reported penicillin allergy tend to get broader, less-targeted, second line antibiotics, which are not as effective in treating the infection and can have more side effects. For example, good old penicillin is still the preferred antibiotic to treat certain serious bacterial infections, such as Streptococcus, which can cause meningitis and infections of the heart valves.
McCready recounts a situation where this happened. “We had a woman who was very sick in the intensive care unit with toxic shock syndrome from Group A Strep. Because she had this label of penicillin allergy, we first gave her vancomycin, an alternative antibiotic. We did skin testing, and she was not allergic. We then gave her the full dose of IV penicillin, and she turned around within 24 hours. With Group A Strep, penicillin is much better than vancomycin. I really think this saved her life.”
Penicllin allergy mislabelling leads to patients being prescribed inferior and more toxic antibiotics. When second line antibiotics are used to avoid penicillin in those with a reported allergy, there is an increased risk of adverse events. These include being readmitted to hospital, kidney injury and increased rates of other infections.
“If we’re unnecessarily avoiding penicillins when they are the antibiotic of choice, it can do more harm than good,” says Leis. “Sometimes the safer thing to do is to actually give the antibiotic despite the penicillin allergy.”
5. You can be tested to verify whether your penicillin allergy is real.
Most people who have had a reaction to penicillin can be safely tested to see whether or not they can take the drug. Testing for the allergy can include skin testing and a graded oral challenge, where increasingly higher doses of penicillin are given by mouth. This is all done in a supervised setting where the person is closely monitored for a reaction. Not everyone with a penicillin allergy is offered testing. The decision to test is based on the history of the allergy.
“We always have to know when the reaction happened and what was the reaction,” says Christine Song, a clinical immunologist and allergist at the University of Toronto. “We also ask about the severity. How was the reaction treated? Did they have to go to the emergency room? Did they need epinephrine or steroids?” These factors determine whether you get tested and how.
Song says not all penicillin allergies are the same. Some people remember having a reaction that is more consistent with a side effect of the drug rather than an allergic reaction. This is thought to be relatively low-risk. They may be told to take the first dose of the medication in their family doctor’s office without any further testing. Others recall reactions that are more consistent with IgE hypersensitivity. These individuals may be often offered a skin test, oral challenge or a combination.
The best time to get tested is when you are well, and not in the situation when you need the penicillin to fight an infection.
“People who are particularly important are women of child bearing age before they become pregnant, as they may need penicillin to treat strep infection during delivery,” says Song. It’s important to note that people who have never had a reaction to the drug are not routinely tested. There is no routine screening for penicillin allergy.
With the advent of the antibiotic era, widespread infectious diseases were no longer the leading cause of death in the developed world. Now, we face a new problem with antibiotics, where their inappropriate use leads to the emergence of ‘superbugs’ – bacteria that are resistant to multiple drugs that once were effective against them. Over labelled, unverified penicillin allergies have a role in this crisis.