“Although the birth hospitalization lasts only a few days, it sets a critical foundation for establishing breastfeeding, which can influence health outcomes like childhood asthma,” said study author Laura Placke Ward MD, IBCLC, FAAP, co-director for the Center for Breastfeeding Medicine at Cincinnati Children’s Hospital Medical Center.

“Our study underscores the importance of hospital practices in supporting exclusive breastfeeding, as these early experiences may impact long-term health,” she added.

The 9,649 subjects included children born between 2017-2019.

The investigators reported that 81% of the children received some breast milk during their birth hospitalization, and 31% of them were fed exclusively with breast milk during their birth hospitalization.

Five percent were eventually diagnosed with asthma during childhood.

After adjusting for sex, race, and insurance status, newborns fed only with breast milk achieved a 22% lower rate of asthma during childhood compared to those who did not receive any breast milk or did not receive breast milk only.

“This finding highlights the need for greater emphasis on supporting and promoting exclusive breastfeeding during the early days of life,” Ward said. “By focusing on these crucial first days, we may impact children’s health and potentially reduce the risk of chronic conditions like asthma.”

In what appears to be a major advancement that offers the promise of relief to food allergy sufferers around the world, the paper published in Nature Materials describes inulin gel-based oral immunotherapy’s success in stopping allergic reactions in mice by, in part, targeting bacteria in the gut. The gel prevented severe allergic reactions during and even after being administered, including reactions to common triggers such as peanuts, egg white and milk.

The research, conducted by an international team of scientists in pharmaceutical sciences, biomedical and chemical engineering, internal medicine and other specialties, proposes that inulin gel addresses the root cause of food allergies, rather than just managing symptoms.

The research was led by James Moon from U-M’s College of Pharmacy. He has  studied inulin’s potential to treat disease for years. He said inulin gel-based therapy holds great promise due to its safety profile and potential for large-scale production.

“Inulin, a widely consumed dietary fiber recognized as safe by the FDA, forms the basis of the gel, making it a feasible and translatable option for clinical use,” said Moon, whose lab develops drug delivery technologies combined with pharmaceutics and engineering to identify ways for  the body to fight disease. Moon is the J. G. Searle Professor of Pharmaceutical Sciences.

While further research and clinical trials are needed to test the findings, the study, which emphasized the role of the small intestine’s microbiota and metabolites in food allergy regulation, opens potentially life-changing new avenues for therapeutic interventions, he said. Other, newer treatment options have seen low uptake due to adverse reactions and spotty effectiveness.

As many as 1 in 3 adults and more than 1 in 4 children have food allergies, a life-altering condition that is getting harder to manage as allergens can be hidden in a variety of foods and drinks, according to the Centers for Disease Control and Prevention.

Food allergies have become a significant concern globally, especially in developed nations, as accidental exposure to allergens can trigger severe reactions, including death.

The research found that inulin gel, specifically formulated with an allergen, normalized the imbalanced intestinal microbiota and metabolites in allergic mice. This normalization led to the establishment of allergen-specific oral tolerance, effectively suppressing allergic reactions to various food allergens.

“The therapy showed long-lasting protection even after the cessation of treatment, indicating its potential for sustained relief from food allergies,” said Fang Xie, a graduate student who also led the studies.

Inulins are a group of polysaccharides and natural storage carbohydrates in more than 36,000 plant species, including wheat, onion, asparagus and chicory, which is most often used to manufacture supplements.

The fiber is also the subject of research and clinical trials investigating its role in treating or leading to better understanding of cancerous tumors, gastrointestinal illnesses, diabetes and other diseases.

The researchers whose work went into the study represent institutions around the world, including the University of Texas M.D. Anderson Cancer Center,  Dongguk University, Seoul, Republic of Korea, Michigan State University, the University of Washington and WPI Immunology Frontier Research Center, Osaka University, Japan. Additionally, researchers from the University of Michigan represent the Biointerfaces Institute, the departments of Pharmaceutical Sciences, Biomedical Engineering, Chemical Engineering and Internal Medicine and the Mary H. Weiser Food Allergy Center.

Disclaimer: Moon declares financial interests for board membership, as a paid consultant, for research funding, and/or as an equity holder in EVOQ Therapeutics and Saros Therapeutics, and U-M has a financial interest in EVOQ Therapeutics, Inc. The other authors declare no competing interests.

https://doi.org/10.1038/s41563-024-01909-w

The research, led by Murdoch Children’s Research Institute (MCRI) in Melbourne and published in Allergy, found two thirds of children with a peanut allergy remain allergic by the age of 10. But for those who did naturally outgrow their allergy, the majority achieved this by six years old.

The study was the first to use antibodies as biomarkers to identify persistent or a resolved peanut allergy during the first 10 years of life in children who naturally outgrew their allergy without clinical intervention.

A rise or drop in the levels of two antibodies (sIgG₄ and sIgE) that respond to peanut allergens were key to determining allergy resolution. Changes in the blood test levels of these two antibodies were detected in children who naturally outgrew their allergy.

Antibody levels measured at diagnosis did not predict who would outgrow their peanut allergy, but changes in these levels over time revealed who was more likely to.

The study involved 156 infants in Melbourne with challenge-confirmed peanut allergy from the HealthNuts study who were followed up at ages four, six and 10 years with questionnaires, skin prick tests, blood tests and oral food challenges.

Peanut allergy resolved in a third of children by 10 years, with nearly all who outgrew the allergy doing so by age four to six.

MCRI researcher Kayla Parker said the findings would help clinicians better identify which children were likely to have an ongoing peanut allergy and ensure they received ongoing education and management.

“Little was known before this research about whether antibodies could be used as biomarkers of naturally resolving peanut allergy during the primary school years,” she said.

“We found the longitudinal changes were more useful in predicting those children on the path to peanut allergy resolution than relying on a single snapshot at one timepoint.”

Ms Parker said regular review of children with a peanut allergy by their allergist was important to ensure they receive the most appropriate clinical care.

“Children allergic to peanut who have decreasing antibody markers may benefit from additional visits with their allergist to determine the right time for follow-up food challenges to confirm if their peanut allergy has resolved,” she said.

“Those with high or increasing levels of these biomarkers are less likely to spontaneously outgrow their peanut allergy and could be prioritised for potential early treatment options if available.

“Currently there is no routinely available treatment for peanut allergy and children should maintain strict peanut allergen avoidance, however innovative treatment options are available through food allergy clinical trials, which are listed on the National Allergy Centre of Excellence’s Allergy Studies Directory.”

It comes as another new study, led by MCRI, found allergic diseases continue to be a significant public health burden in Australian children, with allergies affecting 40 per cent of primary school-aged children and a third having multiple allergies.

Published in The Journal of Allergy and Clinical Immunology: In Practice, the research reported 45 per cent of infants with a food allergy have persistent symptoms to age 10.

Between the ages of six and 10, asthma prevalence remained similar at around 13 per cent, eczema rates decreased from 15 per cent to 13 per cent while hay fever cases increased from 15 per cent to 25 per cent.

MCRI Associate Professor Rachel Peters said the research highlighted the importance of prevention and treatment strategies, particularly for nut allergies, as well as eczema, asthma and hay fever.

“Understanding how allergy prevalence varies across the school years has important implications on informing the burden of disease, allocating healthcare resources and improving school and workforce planning,” she said.

Melbourne mum Vivienne Lai’s daughter, Emilia, 3, has multiple food allergies (cow’s milk, peanut, eggs, cashews and pistachios).

Emilia was first diagnosed with a cow’s milk allergy at 10 months after having an allergic reaction to yogurt.

“She initially was able to tolerate these foods, so it was a huge shock when the allergy test came back positive for so many different allergens,” Vivienne said.

“We try our best to avoid the allergens in places like restaurants and daycare and follow an allergy action plan, but Emilia still has reactions from time to time.”

In her first six months back at work after having Emilia, who was then aged one, Vivienne said she received frequent calls from the daycare centre.

“It was anxiety-inducing for us and the staff who were trying to work out what was trigging the allergic reactions,” she said. We always worry because even if the food label or menu says no traces of a certain food it’s not always accurate.”

Emilia’s most severe allergic reaction came after eating what was thought to be dairy free jelly, the day after her third birthday party.

“We were eating the birthday party leftovers the next day when Emilia started to cough uncontrollably and break out in hives after eating jelly,” Vivienne said.

“We gave her antihistamines, but it only brought the swelling down in her face briefly. Panic started to set in, so we decided to use the EpiPen for the first time and called an ambulance.”

Emilia was treated at hospital and discharged four hours later.

Vivienne said given how life-threatening allergies could be, the latest MCRI around which children were likely to outgrow their peanut allergy was a significant development.

“The finding gives families like ours some certainty to the future,” she said. Even if a blood test showed Emilia wasn’t to outgrow her peanut allergy at least it gives us a plan forward, knowing this is going to be a lifelong challenge and we will need to manage her diet closely.”

Associate Professor Peters and Ms Parker are also members of the National Allergy Centre of Excellence (NACE) and the Centre for Food Allergy Research (CFAR), both based at MCRI to help accelerate allergic disease research across Australia.

Researchers from the University of Melbourne, The Royal Children’s Hospital, Monash Children’s Hospital and the University of Queensland also contributed to the findings.

Publication 1: Kayla M. Parker, Thanh D. Dang, Rushani Wijesuriya, Victoria X. Soriano, Adrian J. Lowe, Shyamali C. Dharmage, Paxton Loke, Mimi L. K. Tang, Katie J. Allen, Jennifer J. Koplin, Kirsten P. Perrett and Rachel L. Peters. ‘Longitudinal peanut and Ara h 2 specific-IgE, -IgG₄ and -IgG₄/-IgE ratios are associated with the natural resolution of peanut allergy in childhood,’ Allergy. DOI: 10.1111/all.16111

Publication 2: Rachel L Peters, Victoria X Soriano, Katrina J Allen, Mimi L. K. Tang, Kirsten P Perrett, Adrian J Lowe, Rushani Wijesuriya, Kayla M Parker, Paxton Loke, Shyamali C Dharmage and Jennifer J Koplin. ‘The prevalence of IgE-mediated food allergy 1 and other allergic diseases in the first 10 years 2 of life: The population-based, longitudinal HealthNuts study. The Journal of Allergy and Clinical Immunology: In Practice. DOI: 10.1016/j.jaip.2024.03.015

*The content of this communication is the sole responsibility of MCRI and does not reflect the views of the NHMRC.

In a new study published in the Journal of Infection funded by the National Institute for Health and Care Research (NIHR), academics and clinicians ran a study in three UK hospitals to assess the feasibility of non-allergy specialist healthcare professionals delivering direct oral penicillin ‘challenges’, without doing allergy tests, where low risk patients who think they have a penicillin allergy receive an oral dose and are closely monitored afterwards.

From more than 2000 potentially eligible patients and following screening, 126 took part in the trial which ran in University Hospitals Birmingham NHS Foundation Trust (UHB), Leeds Teaching Hospitals NHS Trust and Oxford University Hospitals NHS Foundation Trust.

Participants were given an oral dose of amoxicillin by a research nurse or a research pharmacist in a safe clinical environment supervised by a non-allergy specialist clinical consultant, with immediate access to resuscitation facilities if needed.

122 of the 126 participants (97%) were assessed as having no penicillin allergy, with no cases of serious hypersensitivity reactions.

Professor Mamidipudi Thirumala Krishna, Chair of Allergy, Clinical Immunology and Global Health at the University of Birmingham, and corresponding author and Chief Investigator of the study said:

“Inaccurate penicillin allergy labels are a huge burden globally. In High Income Countries such as UK and USA 6-10% percent of the population believe that they are allergic.  Penicillin allergy labels are not benign and contribute to antimicrobial resistance, so enabling more patients to safely benefit from penicillin will ease the burden of other antibiotics that are currently being overused and improve quality of clinical care”.

“In our feasibility study, we showed how a closely monitored protocol for taking penicillin directly, rather than using a skin allergy test which needs to be delivered by an allergy specialist, was effective in low-risk patients. This means they can safely use penicillin in the future”.

Dr Louise Savic, Consultant Anaesthetist and Drug Allergy Specialist at Leeds Teaching Hospitals NHS Trust, Co-Chief Investigator and joint senior author of the study said:

“This study demonstrates that a routine programme of de-labelling people who believe they are allergic penicillin, outside the setting of a specialist allergy clinic, is potentially achievable. Delabelling was particularly successful within the outpatient population, suggesting that future efforts might be best targeted to this group in order to maximise benefit.”

Dr Siraj Misbah, joint-senior author, Consultant Immunologist at Oxford University Hospitals and National Clinical Director for the Blood and Infection Programme at NHSE said:

“Inaccurate labels of penicillin allergy constitute a major public health challenge because of its adverse consequences for the individual due to restricted antibiotic access and for wider public health because of its negative impact on antimicrobial resistance and stewardship. By demonstrating that allied healthcare professionals with no previous background in allergy are capable of removing a penicillin allergy label, this study provides a low-cost framework for adoption by healthcare systems.”

The laboratory-made antibody, omalizumab, is approved by the Food and Drug Administration for three indications other than food allergy. FDA is reviewing a supplemental biologics license application for omalizumab for food allergy based on this interim analysis of the NIAID trial.

In addition to NIAID funding, the trial has support from Genentech, a member of the Roche Group, and Novartis Pharmaceuticals Corporation. The two companies collaborate to develop and promote omalizumab, marketed as Xolair, and are supplying it for the trial.

The multi-stage trial is called Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Children and Adults, or OUtMATCH. The NIAID-funded Consortium for Food Allergy Research (CoFAR) is conducting OUtMATCH at 10 locations across the United States.

The first stage of the study was designed to assess the efficacy of omalizumab in increasing the amount of food it takes to cause an allergic reaction, thereby reducing the likelihood of reactions to small amounts of food allergens in the event of accidental exposure. The study team enrolled children and adolescents ages 1 to 17 years and three adults ages 18 to 55 years, all with confirmed allergy to peanut and at least two other common foods.

In the planned interim analysis, the study’s independent Data and Safety Monitoring Board (DSMB) examined data on the first 165 children and adolescents who participated in the first stage of the trial. Using strict criteria, the DSMB found that study participants who received omalizumab injections could consume higher doses of peanut, egg, milk and cashew without allergic reactions than participants who received placebo injections.

Based on these favorable results, the DSMB recommended halting enrollment into the first stage of the trial. NIAID accepted the board’s recommendation. More detailed information about the findings will become available when they are published in a peer-reviewed journal.

Additional information about the ongoing OUtMATCH trial is available at ClinicalTrials.gov under study identifier NCT03881696.

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.

“We wondered if those who spoke a language other than English would be underdiagnosed for some allergic conditions,” says Hao Tseng, MD, ACAAI member and lead author on the study. “Among children with a language preference other than English, the diagnosis of asthma was less than half as common, eczema was about 2/3 as common, and allergic rhinitis was slightly more than half as  common when compared with children whose preferred language was English. A similar correlation for the diagnosis of food allergy was deemed not statistically significant.

To conduct the study, a retrospective review of electronic health records (EHR) of all patients under 18 years of age who were seen from 7/1/2020 to 4/30/2023 in a primary care pediatric clinic was conducted. A total of 16,517 children were included in the study. The mean age was 6.2 years and 48.6% of children were female. The majority of children were Black (80.4%) and enrolled in Medicaid (78.9%). 14.8% of participants indicated a preference for a language other than English (4% Haitian Creole, 4% Spanish, and 6.5% other).

In an unrelated report of a medically challenging case, a Spanish-speaking 7-year-old girl was diagnosed with a fish allergy and prescribed an epinephrine autoinjector. A school medication form was completed so that the patient could have epinephrine available at school. When the prescription was sent to the pharmacy, the prescription was translated into Spanish using a translation software; however, the software made minor changes. Since the prescription no longer matched the school form exactly, the school nurse did not accept the epinephrine autoinjector, and returned it home with the student and a note. The patient’s mother was unable to read the note because it was written in English. Four months later, the patient returned to clinic with the epinephrine autoinjector and the nurse’s note.

“Patients with limited English proficiency encounter unexpected barriers to care and remain a vulnerable patient population,” says Margaret Huntwork, MD, senior author of the paper. “The pharmacy translation software is not the only thing to blame for this case of a delay in securing a potentially life-saving medication in the school setting. Communication between the family, the physician, the school nurse, and the pharmacy is essential to ensure safety and success of students with allergies.”

Abstract Title:
Language Barriers are Associated with the Underdiagnosis of Allergy and Immunology Conditions in Children

Presenter: Hao Tseng, MD

Medically Challenging Case Abstract Title: Lost in Translation: Pharmacy Translation Software Mounts an Unexpected Barrier to School Medications

Presenter: Geetha Gowda, MS

For more information about allergies and asthma, or to find an allergist in your area, visit AllergyandAsthmaRelief.org. The ACAAI Annual Scientific Meeting is Nov. 9-13. For more news and research from the ACAAI Scientific Meeting, go to our newsroom and follow the conversation on X/Twitter #ACAAI23.

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.

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Why should we de-label ‘penicillin-allergic’ patients?

Penicillin allergy is commonly over-reported and patients are often incorrectly labelled as being allergic to penicillin. Removing incorrect penicillin allergy labels can improve patient care by effectively making penicillin available to patients and reducing unnecessary use of broad-spectrum antibiotics, Mr Hearsey explains.  A detailed allergy history is required to determine whether there is a high or low risk of having a true penicillin allergy. The low-risk group was separated into those eligible for direct de-labelling on history alone and those eligible for direct drug provocation testing.

The British Society of Allergy and Clinical Immunology (BSACI) recently published guidelines to help non-allergists to set up penicillin allergy de-labelling services, he says.

The penicillin allergy de-labelling toolkit contained all of the documentation resources needed to undertake the procedure. The drug provocation test involved giving a dose of penicillin under careful observation.

A total of 56 patients were successfully de-labelled in the pilot study and the next step is to embed this into the standard of care at the hospital.  A key challenge will be preventing the erroneous reappearance of the penicillin allergy label, acknowledges Mr Hearsey.

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