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
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
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