A Study of the Impact of Penicillin Allergy on Antimicrobial Resistance and ouTcomes

NCT ID: NCT07177690

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 214 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-11-30
• Study Completion Date: 2025-12-01

Brief Summary

Penicillin allergy is one of the commonest reported allergies. The presence of a penicillin allergy record in a patients notes leads to the avoidance of recommended first-line penicillin antibiotics and the use of alternative non-penicillin antibiotics which can be less effective, have more side effects and have a greater propensity to drive antimicrobial resistance (AMR). Most patients with penicillin allergy records do not have a true allergy when they are tested by a specialist, so many patients are denied the best antibiotics because of an incorrect penicillin allergy record.

The study will investigate how having a penicillin allergy impacts on treatment for patients who need antibiotics when they are hospitalised with COVID-19 and how penicillin allergy affects AMR.

Antibiotic use is the main driver of AMR, antibiotic use can also disrupt the bacteria that normally live in our guts and mouths. These bacterial communities also known as the gastrointestinal (GI) and oral microbiome respectively, help us digest food and prevent infections. Antibiotic use can 'kill off' these harmless bacteria and lead to an increase in bacteria which have genes that make them resistant to antibiotics (antibiotic resistance genes). The study investigators believe that patients with penicillin allergy are likely to have a greater number of antibiotic resistance genes in their oral and GI microbiomes, ans that this will make it more likely that they will fail antibiotic treatment and will increase their risk of transmitting resistance to others.

The study objectives are:

1. To determine how penicillin allergy impacts on clinical outcomes in patients admitted with COVID-19

2. To find out if AMR genes in the oral microbiome of people with a penicillin allergy record are different to those without a penicillin allergy record

3. To investigate whether AMR genes are lost in patients who have an incorrect penicillin allergy label removed

Detailed Description

Study hypothesis:

Patients with a penicillin allergy record are more likely to have resistance to non-penicillin antibiotics in their normal flora and that this will increase their risk of treatment failure with non-penicillin antibiotics. In particular, penicillin allergic patients admitted with COVID-19 who have bacterial infections will have an increased risk of treatment failure and poor outcomes.

Study design:

This research will be conducted in three separate but complementary workstreams:

Workstream 1 will include secondary analysis of data collected as a part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH) study (ISRCTN66682918) to determine how penicillin allergy impacts on antibiotic use and clinical outcomes in patients admitted with COVID-19. The PEACH study was a multi-centre, retrospective, observational, cohort study using patient-level clinical data which investigated whether the use of procalcitonin testing, to guide antibiotic prescribing, safely reduced antibiotic use amongst hospitalised patients with COVID-19 during the first wave of the pandemic using routinely collected patient institutional clinical databases and patient medical records. Data were collected in 11 National Health Service (NHS) acute hospital Trusts and Health Boards in England and Wales, and data in a pseudo-anonymised format was received from the Cardiff Clinical Trials Unit who were the data controllers for the PEACH study.

Workstream 2 will compare the oral resistome of patients with and without penicillin allergy. Metagenomic and metatranscriptomic analysis will be used for resistome assessment.

Workstream 3 will determine the feasibility of investigating if antibiotic resistance genes are lost after removal of an incorrect penicillin allergy record. This workstream will recruit patients enrolled in the Allergy Antibiotics and Microbial Resistance (ALABAMA) trial (NCT04108637), which is a randomised control trial (RCT) designed to assess the effect of removing incorrect penicillin allergy records on health outcomes. Participants are randomised to either usual care or the intervention group where they receive a novel penicillin allergy assessment pathway (PAAP), if patients in the intervention group are found to be not allergic to penicillin, their allergy label is subsequently removed. Patients recruited to this workstream will be followed up as per the ALABAMA protocol but will also be required to provide baseline and follow up (> 6 months after enrolment or allergy testing) saliva +/- stool samples. Metagenomic and metatranscriptomic analysis will be used for resistome assessment.

Conditions

Penicillin Allergy; Antimicrobial Drug Resistance; AMR

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

Workstream 1: PEACH Study participants

Adults and adolescents 16 years old and older, admitted to hospital between 1/2/20 and 30/06/20 with a positive SARS-CoV-2 test.

No interventions assigned to this group

Workstream 2 exposure group

Adult patients with a penicillin allergy attending immunology clinics at Leeds Teaching Hospitals, UK

No interventions assigned to this group

Workstream 2 comparator group

Adult patients without a penicillin allergy attending immunology clinics at Leeds Teaching Hospitals, UK

No interventions assigned to this group

Workstream 3 exposure group

Participants enrolled in the ALABAMA trial who underwent penicillin allergy testing

No interventions assigned to this group

Workstream 3 comparator group

Participants enrolled in the ALABAMA trial who had usual care only (i.e. did not undergo penicillin allergy testing)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Workstream 1

1. Adult (>16 years) with confirmed COVID-19 (positive PCR test)

2. Admitted to participating NHS Trusts/hospitals between 01/02/2020 to 30/06/2020

• Workstream 2

1. Adult (≥18 years) patients with a penicillin allergy or a matched patients (by age and sex) without a penicillin allergy

2. Received antibiotics in the 24 months prior to recruitment

3. Willing to provide saliva +/- stool samples

• Workstream 3

1. Patients enrolled into the ALABAMA trial

Exclusion Criteria

• Workstream 1

a. Patients with their allergy status missing will be excluded.

• Workstream 2

1. Patients unable to give informed consent or who are unwilling/unable to provide saliva samples

2. Unwilling/unable to provide saliva samples

• Workstream 3

1. Patients unable to give informed consent or who are unwilling/unable to provide saliva samples

2. Unwilling/unable to provide saliva samples

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Leeds

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Sandoe

Associate Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shadia Ahmed, MBChB

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Leeds

Locations

Leeds Teaching Hospitals NHS trust

Leeds, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Version 1. 3 25/01/2022

Identifier Type: -

Identifier Source: org_study_id