Title: PARROT: Penicillin Allergy, Antibiotic Resistance and Patient health OuTcomes
Funder: Department of Health and Social Care

Abstract: BackgroundPatients who have a penicillin allergy (PenA) label are treated with non-penicillin antibiotics, have longer hospital stays, receive repeated courses of antibiotics, and have increased mortality when compared to patients without PenA.Antibiotics used in place of penicillin antibiotics in patients with PenA have a greater tendency to select for antibiotic resistance. This may be contributing to the higher rates of treatment failure and death seen in patients with PenA. Bloodstream infections (BSI) and COVID-19 are serious infections that can cause sepsis. The impact of PenA on AMR and health outcomes in patients treated for BSI and COVID-19 is largely unknown.Aim To understand the associations between PenA, AMR and patient health outcomes in order to inform future antibiotic stewardship policies. ObjectivesThis project will be organised into three workstreams with the following objectives: Workstream-1: To determine the impact of a PenA labels on AMR in patients with bloodstream infections. Workstream-2: To determine the impact of a PenA labels on AMR and patient health outcomes in patients admitted with COVID-19. Workstream-3: To assess if removing incorrect PenA labels will result in a reduction in AMR.MethodsThis fellowship will take advantage of existing big data and collaborate with two NIHR-funded studies: PEACH 'Procalcitonin: Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH)' and ALABAMA 'AntiBiotics, Allergy and Microbial ResistAnce (ALABAMA)' NIHR funded studies.The following methods will be used for each workstream: Worksteam-1: Access the PIONEER Health Data Research Hub, a repository of health data collected as a part of routine NHS care, to identify patients with BSI for a cohort study to explore how PenA impacts AMR and patient health outcomes. PIONEER data are highly detailed with the ability to link BSI diagnoses to AMR and PenA status. Workstream-2: Perform a second cohort study using PEACH Study data to investigate the impact of PenA on AMR, and patient health outcomes in patients admitted with COVID-19. Workstream-3: Undertake a study within the ALABAMA trial, involving longitudinal sampling of ALABAMA participants to investigate whether AMR genes are lost in participants who have had incorrect PenA labels removed.Patient & Public Involvement (PPI)PPI has been embedded since project inception and Jenny Boards (JB), our PPI lead contributor has been involved supporting the project concept, advising on study practicalities, accessibility, and has been invaluable in simplifying the scientific language. JB will continue to advise on this research as a member of Project Management Group. ImpactAMR is predicted to affect 10 million people globally by 2050. Determining the impact PenA has on AMR and health outcomes, ensures this research will have both patient and societal level benefit. It will provide the evidence to support better antibiotic prescribing and in turn mitigate the spread of AMR. Findings from this Fellowship will provide key evidence for the role PenA testing could have on antibiotic stewardship policy to minimise AMR. This research will address a critical research gap expanding our understanding of the mechanism of antibiotic treatment failure in people with PenA.

Lay abstract: JARGON BUSTER:Antibiotic: A medicine used to treat infections caused by bacteria. Antibiotics work by killing bacteria.Antibiotic resistant bacteria: 'Superbugs like MRSA'. Bacteria that have changed so they are no longer killed by antibiotics.Antimicrobial resistance/AMR: A term used to describe the development of antibiotic resistant bacteria.Bloodstream Infection/BSI: A serious infection caused by bacteria in the blood.PARROT: Fellowship study's short name.Penicillins: A common group of antibiotics.Penicillin allergy/PenA: When your immune system reacts abnormally to penicillin, wrongly thinking it is harmful. BACKGROUND:Antibiotic resistant bacteria have a huge impact on patients and the NHS because infections involving these resistant bacteria mean our usual antibiotic treatments will not work as well. People who are affected take longer to get better from common infections and are more likely to die from serious infections e.g.bloodstream infections (BSI). This problem is often called AMR. AMR is caused by overuse and misuse of antibiotics. Penicillins are the first-choice treatment for many common infections. People who have Penicillin allergy/PenA are treated with different, non-penicillin antibiotics. People with PenA are typically prescribed more antibiotics overall, partly because the alternative antibiotics fail to clear the infection. Research has shown that although many people have PenA labels in their notes, most of these people (9 in 10) do not actually have a true allergy when they are tested by a specialist, which means antibiotics are being misused and overused.HEALTH NEED:PenA labels have been linked with 'superbugs', however the full impact of PenA on AMR is unknown. In particular the impact of PenA on AMR and health outcomes in patients treated for BSI and COVID-19 (both of which can cause life-threatening sepsis) is not known.We know that antibiotic use can affect the bacteria that normally live in our guts and mouths. These help us digest food and prevent infections. The more antibiotics are used, the more likely it is that these helpful bacteria are 'killed off', leading to harmful bacteria growing in their place. These harmful bacteria may be able to cause infections, or have genes that make them resistant to antibiotics, or both. See https://youtu.be/r_50QNX0-t0AIM:To understand the links between PenA, AMR and patient health outcomes in order to improve antibiotic use.METHODS:PARROT is organised into three workstreams:Firstly, I will use a large collection of patient data provided by the PIONEER Health Data Research hub, who hold anonymised data on patients admitted hospital. This data will be used to see if PenA patients who have BSI are more likely to have AMR.Secondly, using data from the NIHR funded PEACH study which is investigating antibiotic use in patients with COVID-19, I will carry out a study to find out the effect of PenA on AMR and patient health outcomes in patients admitted with COVID-19.Thirdly, I will work with the ALABAMA trial, a NIHR-funded trial which aims to remove incorrect PenA labels through pencilling allergy testing. I will recruit ALABAMA trial participants, to carry out a study within a trial that will explore if removing incorrect PenA labels results in reduced AMR. PATIENT AND PUBLIC INVOLVEMENT (PPI):Jenny Boards (PPI lead contributor) has brought her 'PenA lived experience' to co-design PARROT, guiding simplification of the scientific language, and ensuring a patient benefit focus.DISSEMINATION:This research will benefit patients, healthcare workers and policymakers by providing the evidence to support better antibiotic prescribing and help limit AMR. It will tell us if removing incorrect PenA labels results in less AMR. Results will be shared through presentations at scientific meetings, publications in journals and a short video co-developed with PPI-contributors.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION