Why penicillin allergy labels might be a bad thing

Penicillin allergy labelling was intended to prevent accidental administration of penicillins to people who had documented allergies to penicillin, but “less than 5% of those people with an allergy record are genuinely allergic to penicillin so we’re denying penicillin in a lot of people”, explains Mr Powell.  In fact, these people receive alternative antibiotics that are associated with increased risks of side effects, longer hospital stays and treatment failure.

About 70% of those with penicillin allergy labels acquired them in childhood.

What the PALACE study tells us about penicillin allergy de-labelling

Distinguishing who has a genuine penicillin allergy amongst all the people who are labelled as “allergic to penicillin” is an important issue.  Traditionally, this has been achieved by referring all individuals labelled as ‘allergic to penicillin’ to an allergist for blood tests (for specific immunoglobulin E (IgE)) and skin prick testing for penicillins followed by an oral challenge with a penicillin. However, the PALACE study has recently shown that in people at low-risk of penicillin allergy, a direct oral challenge is all that is needed to determine their penicillin allergy status. In this study the PEN-FAST score was used to identify people at low-risk of true penicillin allergy.

Could penicillin allergy de-labelling lead to better outcomes?

It is estimated that up to four million people in the UK could be incorrectly labelled as having an allergy to penicillin. Mr Powell’s research is exploring the implementation of penicillin allergy de-labelling as a standard of care for hospitalised patients. An understanding of the key barriers and enablers in healthcare systems is an essential pre-requisite.  The ALABAMA (ALlergy AntiBiotics And Microbial resistance) study aimed to identify patients from GP records who had low-risk penicillin allergy records, randomise them to ‘allergy-testing’ or ‘not allergy-testing’ (usual care) and then to follow them up to see whether those that had been de-labelled had different health outcomes from those that had not been de-labelled.  The ALABAMA study also investigated patient and GP perspectives of penicillin allergy de-labelling and incorporated a behavioural package to remove some of the barriers.  Part of this was designed to optimise the intervention to ensure that both GPs and patients understood what has been done and that once a patient has been de-labelled, they change their behaviour i.e., prescribe or consume penicillin “and to not continue avoiding it, otherwise the intervention of de-labelling is lost”, says Mr Powell.

The iNAAN (International Network of Antibiotic Allergy Nations) project is a multicentre, observational study of penicillin de-labelling. One of the objectives is to determine the impact of de-labelling, in particular, “to see whether undoing the label undoes the harms”, says Mr Powell.

What does a consultant antimicrobial pharmacist do?

The work of a consultant antimicrobial pharmacist involves not only knowing about antimicrobial medicines but also understanding how people and organisations behave and collaborating with others to optimise antimicrobial prescribing and improve patient care. For example, one important aspect of penicillin allergy de-labelling is ensuring that the incorrect penicillin allergy label does not reappear later, for example, as a result of human error or computer error. This involves working with other health care practitioners and with patients to ensure that all parties understand what has been done and what it means for individuals.

Mr Powell describes his work as a consultant antimicrobial pharmacist as being both demanding and rewarding and he would recommend it to others.

About Neil Powell

Neil Powell is a consultant antimicrobial pharmacist at the Royal Cornwall Hospital. As Associate Director of Antimicrobial Stewardship (for two days a week) he is responsible for ensuring that the hospital is delivering on its antibiotic stewardship program of work. In addition, outside of the hospital he is responsible for ensuring that antibiotic prescribing is appropriate in primary care and the community hospitals. The remaining three days each week are devoted to research – Mr Powell is an NIHR and Health Education England (NIHR/HEE) funded clinical doctoral research fellow.

Read and watch the full series on our website or on YouTube.

One important aspect of penicillin allergy de-labelling is ensuring that the incorrect label does not reappear later, for example, as a result of human error or a computer error.  The key to dealing with this is understanding why the label might creep in. Mr Powell says: “The ALABAMA study really sets out to try and address that …… So, we try and prevent it creeping back in by ensuring the patient understands what a negative test means and what it means for them, to ensure they’re motivated and feel safe to take penicillin in the future. You also ensure it by making sure there’s an authoritative letter about the negative challenge test so the GP has confidence that when they see this letter the patient’s gone through a rigorous de-labelling process that is robust and they can have confidence in the negative test”.  He adds: “You can imagine if [as a GP] you just get a one line note from hospital ……. that says ‘this patient is not allergic to penicillin, please remove it from your records’ you can be pretty anxious about doing that without knowing who’s recommending that [and] why you’re recommending that”.  He acknowledges that this is an important area that will require ongoing work.

Learning about penicillin allergy de-labelling

For people who wish to establish penicillin allergy de-labelling projects in their own hospitals a number of resources are available.  Mr Powell suggests that useful starting points would be the British Society for Allergy and Clinical Immunology (BSACI) guideline for non-allergists and the algorithm produced by Sneddon and colleagues in Scotland. In addition, the British Society for Antimicrobial Chemotherapy (BSAC) is due to launch a massive, open, online community (MOOC) learning module on penicillin allergy de-labelling towards the end of October (2023).

Working as a consultant antimicrobial pharmacist

Mr Powell thoroughly enjoys his work as a consultant antimicrobial pharmacist and would recommend it to others. The job is about changing antibiotic prescribing for the better – optimising prescribing to improve patient care.  However, this involves more than the technical knowledge about antibiotic therapy.  Taking the example of reducing antibiotic course lengths, he explains: “So, you know the literature really supports reducing antibiotic course lengths for common infections but yet we don’t do it and even if you put it in your guidelines people don’t do it.  The reason for that is around behaviour change and we’ve ignored behaviour change. When we try to change behaviour, we don’t tap into the principles of behaviour change – and for me, learning about behaviour change has been hugely interesting. So, as a pharmacist, I spend a lot of my time working out first of all what we need to do – that’s fairly easy -…….  but how we do it is a real challenge. It’s a big meaty problem and that takes a lot of thinking, a lot of talking to others [and] a lot of collaboration, which I enjoy”.

“It’s not about how the tablet works – and you know we know that and that’s really interesting and that’s why we get into Pharmacy – but my role is around changing practice and how we work. It’s a harder thing to do and a more rewarding thing once you’ve achieved it and you can achieve it and so that’s why I enjoy it and that’s why I would recommend it”, he concludes.

About Neil Powell

Neil Powell is a consultant antimicrobial pharmacist at the Royal Cornwall Hospital. As Associate Director of Antimicrobial Stewardship (or two days a week) he is responsible for ensuring that the hospital is delivering on its antibiotic stewardship program of work. In addition, outside of the hospital he is responsible for ensuring that antibiotic prescribing is appropriate in primary care and the community hospitals. The remaining three days each week are devoted to research – Mr Powell is an NIHR and Health Education England (NIHR/HEE) funded clinical doctoral research fellow.

Read and watch the full series on our website or on YouTube.

It is estimated that up to four million people in the UK could be incorrectly labelled as having an allergy to penicillin. Neil Powell’s research is exploring the implementation of penicillin allergy de-labelling as a standard of care for hospitalised patients. In Australia hospitals are already expected to risk-assess ‘penicillin allergic’ patients and de-label, if appropriate whereas in the UK this is currently an ambition, he says.  “My fellowship looks at what the potential barriers to implementation of the penicillin allergy de-labelling tool might be and what the enablers are …… and then trying to work out how we remove barriers and bring in the enablers”, he explains.  This is part of a wider project involving other hospitals in England (including Imperial, King’s, Papworth and Bristol) as part of the iNAAN study that is being coordinated from Australia. As part of his work Mr Powell has interviewed many patients who have undergone de-labelling and many healthcare workers to find out more about their concerns and the barriers to behaviour change.

The International Network of Antibiotic Allergy Nations (iNAAN)

Some 39 hospitals in Australia have signed up to the iNAAN project. Five hospitals in the UK are participating, with the Royal Cornwall Hospital playing a central role. In addition, hospitals in Canada, South Africa and The United Arab Emirates are participating. Each hospital implements penicillin allergy de-labelling according to its own, approved local guidelines and procedures. “They’ll be delivered differently in each hospital – it might be pharmacist doing it, it might be nurses doing it, it might be one enthusiast doing it – how it’s done is up to the hospital with their own guidelines. …..It’s a data collection study where patients who are identified with the penicillin allergy record are risk-assessed and from that point onwards their data is collected”, explains Mr Powell.

The data will then be analysed centrally by the investigators in Melbourne, Australia.  One key aspect of the study is to interrogate the data “to see whether if you undo the label, does that change prescribing? does it change the types of antibiotics used? ….. but more importantly, does it change patient outcomes? does it change mortality? does it change length of stay? Penicillin allergy records are associated with increased mortality [and] increased length of stay; if you undo the label, does it bring about the change?”, he says.   A randomised, controlled study would require vast numbers of patients but this type of study is the next best thing, “to see whether undoing the label undoes the harms”, he notes.  Data collection is expected to continue for 10 years.

ALABAMA – ALlergy AntiBiotics And Microbial resistAnce

The ALABAMA study has now finished recruiting and results are expected soon. It is a multicentre, randomised, pragmatic trial and the Royal Cornwall Hospital was one of the participating sites.  “The main aim is to identify patients from GP records who have got a penicillin allergy record, identify which of those are low-risk, randomise them to ‘allergy-testing’ or ‘not allergy-testing’ (usual care) and then to follow patients up to see whether those that have been de-labelled have different health outcomes from those that haven’t been de-labelled”, explains Mr Powell.

The ALABAMA study also incorporates a “a big behavioural component …. where they’ve looked at [the] patient perspective and GP perspectives around penicillin allergy records and penicillin allergy testing and ……. investigated what the potential barriers might be for GPs referring patients for allergy testing. … Also, what patients understand and what healthcare workers understand about what a negative penicillin allergy test means and whether they believe that test and whether or not they would continue to avoid penicillin in the future even if they have a negative penicillin allergy test. So, as part of that, they’ve come up with a behavioural package which helps remove some of the barriers”, he says.  Part of this is designed to optimise the intervention to ensure that both GPs and patients understand what has been done and that once a patient has been de-labelled, they change their behaviour i.e., prescribe or consume penicillin “and to not continue avoiding it, otherwise the intervention of de-labelling is lost”, says Mr Powell.

About Neil Powell

Neil Powell is a consultant antimicrobial pharmacist at the Royal Cornwall Hospital. As Associate Director of Antimicrobial Stewardship (or two days a week) he is responsible for ensuring that the hospital is delivering on its antibiotic stewardship program of work. In addition, outside of the hospital he is responsible for ensuring that antibiotic prescribing is appropriate in primary care and the community hospitals. The remaining three days each week are devoted to research – Mr Powell is an NIHR and Health Education England (NIHR/HEE) funded clinical doctoral research fellow.

Read and watch the full series on our website or on YouTube.

Distinguishing who has a genuine penicillin allergy amongst all the people who are labelled as “allergic to penicillin” is an important issue.  Traditionally, this has been achieved by referring all individuals labelled as ‘allergic to penicillin’ to an allergist for blood tests (for specific immunoglobulin E (IgE)) and skin prick testing for penicillins. People who were negative for both would then be offered an oral dose of penicillin.  “If the patient didn’t react you would say they’ve got no evidence or they’re not going to have an immediate reaction to penicillin. Then, they traditionally were sent home with a few days of penicillin – three to five days – and if there was no reaction at the end of that period then you could remove the allergy record”, explains Mr Powell.  This was a resource-intensive procedure and it has gradually become clear that blood tests and skin tests are not required for people at low risk of having a true penicillin allergy. “You don’t need to do the blood test for IgE and you don’t need to do the skin testing because they’re always negative in these low-risk patients”, he says. However, this requires a simple scheme for risk-stratifying people who have been labelled ‘allergic to penicillin’.

The PALACE study was a randomised, controlled trial (RCT) that prospectively looked at the safety and effectiveness of a direct oral penicillin challenge compared with the standard of care penicillin skin testing followed by an oral challenge. The participants were people who had a PEN-FAST score of less than 3. “PEN-FAST is a scoring system that you can use. So, you take an allergy history from a patient and depending what the patient’s allergy history is – if it’s got a score of zero, one or two that that would be deemed a low-risk allergy history”, explains Mr Powell. “What they wanted to do was to test that PEN-FAST decision rule against the current gold standard, which is still skin testing then oral challenge. So, they identified a group of patients prospectively who had a low-risk penicillin allergy – so a PEN-FAST score of less than three – and randomised those patients to go straight to oral challenge or to have skin testing first and then oral challenge to see whether the PEN-FAST rule was as good, if you like, as the gold standard – and the answer is yes, it is”, he says.

By doing a robust, prospective, randomised study in this way the researchers have provided validation of the approach and that will give clinicians more confidence to use it. “The beauty of the PEN-FAST [tool] is that it is quick and easy. It’s a very simple three questions [that] gives you a score – [and you can] do something with it whereas the other tools, maybe you’ve got to ask six questions and it’s a bit more involved …… but the PEN-FAST is quick and easy and it’s numbers based”, he says.

About Neil Powell

Neil Powell is a consultant antimicrobial pharmacist at the Royal Cornwall Hospital. As Associate Director of Antimicrobial Stewardship (or two days a week) he is responsible for ensuring that the hospital is delivering on its antibiotic stewardship program of work. In addition, outside of the hospital he is responsible for ensuring that antibiotic prescribing is appropriate in primary care and the community hospitals. The remaining three days each week are devoted to research – Mr Powell is an NIHR and Health Education England (NIHR/HEE) funded clinical doctoral research fellow.

Read and watch the full series on our website or on YouTube.

Penicillin allergy labelling was intended as a safety feature to prevent accidental administration of penicillins to people who had documented allergies to penicillin, but the unintended consequence has been that people who are not genuinely allergic to penicillin are denied these antibiotics. “Penicillin allergy records are common and 15% of hospitalized patients have a penicillin allergy record but, you know, less than 5% of those people with an allergy record are genuinely allergic to penicillin so we’re denying penicillin in a lot of people”, explains Mr Powell.  “In being risk averse like that actually ….. we’re realising we’re causing more harm”, he adds.

“By using alternative antibiotics, we increase patients’ risk of treatment failure and mortality, we increase their lengths of stay, we increase their risk of side effects ……. they are getting potentially inferior treatment with negative consequences”, he says.

One important question here is how people acquire an erroneous penicillin allergy label in the first place. About 70 percent of those with penicillin allergy labels acquire them during childhood, Mr Powell says. “One quite common reason is childhood rashes. So, if you have a child with a sore throat or an upper [respiratory] tract infection – they’re often caused by viruses sometimes by bacteria – but those infections can cause skin rashes. So, what used to happen was …… children come to see a doctor or healthcare worker with a viral infection, get given antibiotics – penicillin – for that viral infection and then they break out in a rash a few days later. That’s often pinned on the penicillin and actually it was the viral infection that caused the rash”, he explains.  Another common reason is any episode of diarrhoea, nausea or vomiting associated with penicillin treatment was mislabelled as an allergy.  Sometimes mild rashes are caused by penicillin exposure but it does not recur on re-exposure to penicillin. “So, it could be penicillin, could be a T- cell mediated skin reaction but actually the immunity is not remembered and it doesn’t re-react in the same way”, he says.  Finally, some people do have IgE-mediated reactions such as anaphylaxis and angio-oedema but the penicillin-specific IgE wanes over time so that over a 10-year period “80% of people lose their IgE to penicillin so they don’t then react in the same way further down the line”, he says.

About Neil Powell

Neil Powell is a consultant antimicrobial pharmacist at the Royal Cornwall Hospital. As Associate Director of Antimicrobial Stewardship (or two days a week) he is responsible for ensuring that the hospital is delivering on its antibiotic stewardship program of work. In addition, outside of the hospital he is responsible for ensuring that antibiotic prescribing is appropriate in primary care and the community hospitals. The remaining three days each week are devoted to research – Mr Powell is an NIHR and Health Education England (NIHR/HEE) funded clinical doctoral research fellow.

Read and watch the full series on our website or on YouTube.