Condition category
Infections and Infestations
Date applied
18/02/2020
Date assigned
20/02/2020
Last edited
19/02/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Bacteria that are resistant to antibiotics are becoming an important problem in hospitals and much research has been carried out to try to reduce the rates. Unwell patients in hospital who have received long antibiotic courses have a high risk of developing infections with antibiotic-resistant bacteria. Patients who are in the community and have received long courses of antibiotics may be at risk but few studies have been done to explore this. Therefore, this study will help clinicians understand how gut bacteria changes, and may become more resistant, after a long course of antibiotics, in a community-based population. In the future this could help clinicians choose better antibiotics for each individual patient. It could help stop the spread of antibiotic-resistant bacteria in hospital by showing when clinicians need to use special infection control measures such as the use of gloves, aprons or gowns, or ensuring certain patients have their own toilet or room.

Who can participate?
Patients aged 18 or older who are expected to receive 2 or more weeks of IV antibiotics, and Infectious Diseases ward or clinic patients who have received no antimicrobial therapy within the last 3 months

What does the study involve?
This study explores how gut bacteria change and develop resistance in patients who have received long courses of intravenous antibiotics in the community. It compares bacteria in stool from participants who have received different intravenous antimicrobials (Outpatient Parenteral Antimicrobial Therapy (OPAT) patients) to participants who have not (a control group). Stool samples will be examined at enrolment, weekly during antimicrobial therapy, at 3 and 6 months. The OPAT group will provide a minimum of 4 stool samples and the control group will provide 3 stool samples. The OPAT group will provide more stool samples than the control group as they will have additional weekly stool samples collected at the time of their routine OPAT clinic visits. All stool samples will be self-collected by the participant and then handed to the study team. At the start of the study, the study team will collect the participant's clinical information from the medical records. This will include the following information: NHS number, date of birth, gender, ethnicity, weight, smoking status, alcohol intake, dietary requirements, probiotic or prebiotic use, travel abroad, contact with hospital in the last year, medical/surgical history, antibiotic use, medication history and any relevant symptoms they may have (such as diarrhoea or vomiting.) The weekly face-to-face return visits to OPAT clinic are part of the usual care if the participant is receiving therapy. At return visits the participant will be asked about any relevant symptoms they may have (such as diarrhoea or vomiting,) any new hospital contact, infections or recent antibiotics they may have received since their last visit. The 3 and 6 month follow up visits may be completed face-to-face or remotely, via telephone consultation, with the study team member. At 3 and 6 month return visits the participant will be asked about any relevant symptoms they may have (such as diarrhoea or vomiting), any new hospital contact, infections or recent antibiotics they may have received since their last visit. The 6-month visit marks the end of the study period for each participant.

What are the possible benefits and risks of participating?
There are no direct benefits to participants for taking part in the study. However, the information that the study team obtain from the study may help future patients and enable doctors to reduce the spread of antibiotic-resistant gut bacteria. There are no direct risks to participants if they take part in this study. There may be some inconvenience associated with the donation of stool samples during the study, as they need to be dropped off at the clinic, at the 3 and 6 month follow up period, by the participant, friend or family member. If the participant is found to have antibiotic-resistant gut bacteria they will be informed and should not be concerned. This information will be recorded in their medical electronic records so that it can be used in the future to ensure they receive the right antibiotics and, if necessary, access to a private room.

Where is the study run from?
Addenbrooke’s Hospital, CUH NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
September 2019 to February 2021

Who is funding the study?
1. Academy of Medical Sciences and the Health Foundation (UK)
2. National Institute for Health Research (UK)

Who is the main contact?
1. Dr Estee Torok
et317@cam.ac.uk
2. Dr Rachel Bousfield
rachel.bousfield@addenbrookes.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Estee Torok

ORCID ID

Contact details

Principal Investigator
Department of Medicine
Box 157
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336845
et317@cam.ac.uk

Type

Public

Additional contact

Dr Rachel Bousfield

ORCID ID

Contact details

Department of Medicine
Box 157
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336845
rachel.bousfield@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

A095421, IRAS 273856

Study information

Scientific title

Evolution of antimicrobial resistance in patients receiving outpatient parenteral antimicrobial therapy

Acronym

Study of AMR in OPAT patients

Study hypothesis

1. How does the gut bacteria change, and does it become more resistant, after a long course of antibiotics in a community-based group of patients compared to those that have not received any antibiotics?
2. Specifically, are there differences that can be detected by testing for gut bacteria's antibiotic-resistance genes and does this difference affect the patient's health by increasing the chance of difficult-to-treat infections?
3. Also, are there differences we can detect by looking for the presence of resistant bacteria including multi-drug resistant organisms (MDRO) and does this difference affect the patient's health by increasing the chance of difficult to treat infections?

Ethics approval

Approved 23/01/2020, East Midlands - Derby Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; Tel: +44 (0)2071048285; Email: NRESCommittee.EastMidlands-Derby@nhs.net), REC ref: 20/EM/0009

Study design

Prospective observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Antimicrobial resistance (AMR)

Intervention

This study involves 4 groups. Each group contains 10 patients:
Group 1: have not received intravenous antimicrobials
Group 2: have received the intravenous antimicrobial ceftriaxone
Group 3: have received the intravenous antimicrobial ertapenem
Group 4: have received the intravenous antimicrobial daptomycin

Eligible participants will have been approached by a study team member during routine clinical care, will have discussed the study, and been provided with written information: the Participant Information leaflet. Participants who decide to take part in the study will sign a Consent form at enrolment.

The study team will collect stool samples from participants at the start of the study and later at approximately 3 and 6 months. The Outpatient Parenteral Antimicrobial Therapy (OPAT) group will provide a minimum of 4 stool samples and the "control" group will provide 3 stool samples. The OPAT group will provide more stool samples than the control group as they will have additional weekly stool samples collected at the time of their routine OPAT clinic visits. All stool samples will be self-collected by the participant and then handed to the study team.

At the start of the study, the study team will collect the participant's clinical information from the medical records. This will include the following information: NHS number, date of birth, gender, ethnicity, weight, smoking status, alcohol intake, dietary requirements, probiotic or prebiotic use, travel abroad, contact with hospital in the last year, medical/surgical history, antibiotic use, medication history and any relevant symptoms they may have (such as diarrhoea or vomiting).

The weekly face-to-face return visits to OPAT clinic are part of the usual care if the participant is receiving therapy. At return visits the participant will be asked about any relevant symptoms they may have (such as diarrhoea or vomiting), any new hospital contact, infections or recent antibiotics they may have received since their last visit.

The 3 and 6 month follow up visits may be completed face-to-face or remotely, via telephone consultation, with the study team member. At 3 and 6 month return visits the participant will be asked about any relevant symptoms they may have (such as diarrhoea or vomiting,) any new hospital contact, infections or recent antibiotics they may have received since their last visit. The 6-month visit marks the end of the study period for each participant.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Number of participants with stool carriage of specific Antimicrobial Resistance Genes (ARGs), measured using DNA/RNA extraction and testing using multiplex PCR for selected targets, at baseline, during antimicrobial therapy, and at 3 and 6 months
2. Number of participants with phenotypic evidence of Antimicrobial Resistance (AMR) organisms, measured using chromogenic agar for CPE, ESBL and VRE with resistant organisms undergoing identification using MALDI TOF MS (Bruker) and antimicrobial susceptibility testing using the Vitek-2 system (BioMerieux), at baseline, during antimicrobial therapy, and at 3 and 6 months
3. Number of participants with significant changes in the faecal microbiome diversity, measured using DNA library preparation and high-throughput microbial whole-genome sequencing, at selected timepoints including, for example, at baseline and 3 and 6 months

Secondary outcome measures

1. Risk factors for carriage of ARGs, measured using correlation between the presence of ARGs and the presence of certain clinical characteristics at baseline
2. Clinical outcomes of patients with AMR organisms (e.g. clinical deterioration or death), measured using correlation between the presence of AMR organisms and the presence of certain clinical characteristics, within the 6-month follow-up period

Overall trial start date

16/09/2019

Overall trial end date

18/02/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adult (age 18 years older)
2. Male or female
3. Cases: patients expected to receive 2 or more weeks of IV antibiotics
4. Controls: an Infectious Diseases ward or clinic patient who has received no antimicrobial therapy within the last 3 months

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. Patients with known previous MDRO colonisation (e.g. ESBL, CPE, VRE)
2. Those known to be pregnant
3. Does not fulfil study inclusion criteria
4. Declines or are unable to consent

Recruitment start date

19/02/2020

Recruitment end date

21/10/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrooke’s Hospital, CUH NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Department of Medicine
Box 157
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 348468
lucy.bennett@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.cuh.org.uk/

Organisation

University of Cambridge

Sponsor details

Department of Medicine
Box 157
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336845
et317@cam.ac.uk

Sponsor type

University/education

Website

https://www.cam.ac.uk

Funders

Funder type

Government

Funder name

Academy of Medical Sciences and the Health Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Protocol not available in web format, please use contact details to request a copy of the protocol.

The study team plan to disseminate the results of the study using peer-reviewed scientific journals, internal reports and conference presentations. They aim to do this in a timely fashion and before 01/01/2023.

It is recognised that the participants may be interested to hear how they contributed to Antimicrobial Resistance research. Therefore, the participants will be offered the opportunity to contact the study team (via the contact details on the participant information leaflet) one year after completion of the study. Those that do this, and give the relevant written permissions, can receive an email or posted printed summary of anonymised data.

IPD sharing statement
The dataset will be held at Addenbrooke’s Hospital, CUH NHS Foundation Trust, UK. It will not be made fully available as the dataset will contain patient identifiable information and clinical details regarding medical conditions and treatment outcomes.

Intention to publish date

01/01/2023

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/02/2020: Trial's existence confirmed by East Midlands - Derby Research Ethics Committee.