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

NCT07177690 | Active Not Recruiting

• 1 other identifier: Version 1. 3 25/01/2022
• Study Type: observational
• Target: 214
• Locations: 1 country
• Sites: 1

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. 1.To determine how penicillin allergy impacts on clinical outcomes in patients admitted with COVID-19
2. 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. 3.To investigate whether AMR genes are lost in patients who have an incorrect penicillin allergy label removed

Conditions

Penicillin Allergy; Antimicrobial Drug Resistance; AMR

Keywords

penicillin allergy; AMR; Antimicrobial resistance

Outcome Measures

Primary Outcomes (3)

• Workstream 1: 60 day mortality in patients with and without penicillin allergy

  This outcome will measure mortality within 60 days of positive COVID-19 test. Comparative analysis will be conducted between patients with and without a documented penicillin allergy.

  60 days from the date of positive COVID 19 test

• Workstream 2: The prevalence of antibiotic resistance genes (ARGs) in the mouth of patients with and without a penicillin allergy record.

  The prevalence of ARGs will be assessed using shotgun metagenomic sequencing of saliva samples. Comparative analysis will be conducted between patients with and without a documented penicillin allergy.

  At enrolment

• Workstream 3: Change in abundance of antibiotic resistance genes in saliva samples collected from participants enrolled in the ALABAMA trial

  This outcome will determine the change in antibiotic resistance gene (ARG) abundance over time in patients who received the ALABAMA trial intervention (penicillin allergy assessment) compared to those in the control group (no penicillin allergy assessment). This analysis will focus on the subset of ALABAMA trial patients with at least one antibiotic prescription prior to their second saliva sampling. Comparative analysis will be conducted between the penicillin allergy assessment group and the no penicillin allergy assessment group.

  At enrolment (first sample collection) and 6 to 12 months post-enrolment (second sample collection)

Secondary Outcomes (13)

• Workstream 1: Length of hospital stay in patients with and without a penicillin allergy.

  Time of hospital admission to discharge or inpatient death for each patient, assessed up to 600 days

• Workstream 1: Number of AMR bacterial infections in patients with and without a penicillin allergy.

  Time of hospital admission to discharge or inpatient death for each patient, assessed up to 600 days

• Workstream 1: Total antibiotic usage in patients with and without a penicillin allergy.

  Time of hospital admission to discharge or inpatient death for each patient, assessed up to 600 days

• Workstream 1: Rates of treatment failure in patients with and without a penicillin allergy.

  Time of hospital admission to discharge or inpatient death for each patient, assessed up to 600 days

• Workstream 1: ICU admission rates in patients with and without a penicillin allergy.

  Time of hospital admission to discharge or inpatient death for each patient, assessed up to 600 days

Other Outcomes (5)

• Workstream 3: To determine the number of patients from the ALABAMA trial who consented to participate in this sub-study.

  From the start of recruitment until the end of the recruitment period, estimated to last up to 5 years

• Workstream 3: To determine the number of patients who provide baseline samples

  At enrolment

• Workstream 3: To determine the number of patients who provide a second sample

  Six to twelve months post-enrolment

Study Arms (5)

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.

Workstream 2 exposure group

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

Workstream 2 comparator group

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

Workstream 3 exposure group

Participants enrolled in the ALABAMA trial who underwent penicillin allergy testing

Workstream 3 comparator group

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

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

\- Workstream 1 population: Participants included in the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH) study (ISRCTN66682918) \- Workstream 2 population: Participants will be recruited from patients attending outpatient clinics at Leeds Teaching Hospitals NHS Trust, United Kingdom. \- Workstream 3 population: Participants will be recruited from the population of patients participating in the he Allergy Antibiotics and Microbial Resistance (ALABAMA) trial (NCT04108637).

You may qualify if:

• Workstream 1
• Adult (\>16 years) with confirmed COVID-19 (positive PCR test)
• Admitted to participating NHS Trusts/hospitals between 01/02/2020 to 30/06/2020
• Workstream 2
• Adult (≥18 years) patients with a penicillin allergy or a matched patients (by age and sex) without a penicillin allergy
• Received antibiotics in the 24 months prior to recruitment
• Willing to provide saliva +/- stool samples
• Workstream 3
• Patients enrolled into the ALABAMA trial

You may not qualify if:

• Workstream 1
• a. Patients with their allergy status missing will be excluded.
• Workstream 2
• Patients unable to give informed consent or who are unwilling/unable to provide saliva samples
• Unwilling/unable to provide saliva samples
• Workstream 3
• Patients unable to give informed consent or who are unwilling/unable to provide saliva samples
• Unwilling/unable to provide saliva samples

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds Teaching Hospitals NHS trust

Leeds, United Kingdom

Location

Study Officials

• Shadia Ahmed, MBChB

  Univeristy of Leeds

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: September 17, 2025
• Study Start: November 30, 2021
• Primary Completion: April 24, 2024
• Study Completion: December 1, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Locations

GB (1)