A Study of the Impact of Penicillin Allergy on Antimicrobial Resistance and ouTcomes
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Workstream 1: 60 day mortality in patients with and without penicillin allergy
研究概览
简要总结
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:
- To determine how penicillin allergy impacts on clinical outcomes in patients admitted with COVID-19
- 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
- To investigate whether AMR genes are lost in patients who have an incorrect penicillin allergy label removed
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Workstream 1: 60 day mortality in patients with and without penicillin allergy
时间窗: 60 days from the date of positive COVID 19 test
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.
Workstream 2: The prevalence of antibiotic resistance genes (ARGs) in the mouth of patients with and without a penicillin allergy record.
时间窗: At enrolment
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.
Workstream 3: Change in abundance of antibiotic resistance genes in saliva samples collected from participants enrolled in the ALABAMA trial
时间窗: At enrolment (first sample collection) and 6 to 12 months post-enrolment (second sample collection)
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.
次要结局
- 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)
- Workstream 1: Rate of Clostridioides difficile infection 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: 30 day mortality in patients with and without a penicillin allergy(30 days from COVID-19 diagnosis)
- Workstream 2: The difference in diversity of antibiotic resistance genes (ARGs) in oral microbiome of patients with and without a penicillin allergy record.(Enrolment)
- Workstream 2: The number of resistance genes to specific antibiotic classes present in the oral microbiome of patients with and without a penicillin allergy record.(Enrolment)
- Workstream 2: To determine whether a metagenomic or transcriptomic approach could be used to predict phenotypic antibiotic susceptibility(Enrolment)
- Workstream 3: The change in the abundance and richness of antibiotic resistance genes (ARGs) over time between patients who had the ALABAMA trial intervention and those in the control group(At enrolment (first sample collection) and 6 to 12 months post-enrolment (second sample collection).)
- Workstream 3: The number and abundance of 'non-penicillin' antibiotic resistance genes in patients who had the ALABAMA trial intervention (penicillin allergy assessment) and those in the control group (no penicillin allergy assessment).(At enrolment (first sample collection) and 6 to 12 months post-enrolment (second sample collection))
- Workstream 3: The number and abundance of 'penicillin' antibiotic resistance genes (ARGs) in patients who had the ALABAMA trial intervention (penicillin allergy assessment) and those in the control group (no penicillin allergy assessment).(At enrolment (first sample collection) and 6 to 12 months post-enrolment (second sample collection).)
研究者
Jonathan Sandoe
Associate Clinical Professor
University of Leeds