Feasibility Studies to Inform Novel Proposals to Avert Community-Based Antimicrobial Resistance Spread

There are many bacteria that naturally live in our gut and are essential for good health. These bacteria have a variety of helpful functions, such as aiding digestion, synthesizing vitamins, repressing the growth of harmful bacteria and defending against some diseases. The desirable bacteria that live in the gut are collectively known as 'gut flora', or more appropriately, as 'gut microbiota'.

The less desirable resistant bacteria, however, can also be carried in a person's gut for prolonged periods of time and be found in the stools without causing illness. Persons that carry the resistant bacteria in the gut are known as "carriers" and they require no treatment. Knowing that a person carries resistant bacteria is helpful, because it will inform the choice of antibiotic if the person were to become unwell or had an intervention such as surgery in the future.

There is some evidence that resistant bacteria found in the stools can sometimes be passed from one person to another and eventually make someone ill if they infect (invade) their body. The investigators do not know how often this may happen, or how much carrying resistant bacteria in the stools may facilitate the spread of resistant bacteria in the population. It is important to address these questions and study ways to stop the resistant bacteria from spreading to safeguard the efficacy of antibiotics.

Study Overview

• Status: Unknown
• Conditions: Gram-Negative Bacterial Infections

Detailed Description

1. Study A. Mapping of resistant gram negative bacteria (RGNB) in the community: Based on RGNB clinical isolates as a proxy for gut colonising RGNB and residential Lower Layer Super Output Area (LSOA) data retrieved from laboratory information systems of a hospital cohort, to describe the geographical distribution of RGNB in South East London in relation to demographic, cultural and socioeconomic indicators and to investigate whether geographical clustering of resistance, compatible with the occurrence of community based transmission hotspots, occurs in our local community.
2. Study B. Tracking gut colonisation with carbapenem resistant Klebsiella spp. or Klebsiella spp. resistant to third generation cephalosporins (3GC), herein referred to as 'Resistant Klebsiella' (RK):

To investigate the duration of gut colonisation with Klebsiella spp. in a small cohort of discharged hospital patients with resistance to the carbapenems (eg. meropenem), defined by presence of either blaKPC, blaNDM, blaIMP , blaVIM or blaOXA48 genes, or Klebsiella spp. with resistance to the 3GC (eg. ceftazidime), defined by presence of blaCTX_M or AmpC βlactamase genes. To determine the occurrence of participant to participant RK transmission events within a household, in relation to gut bacterial load and the gut microbiota profile. To characterise over time, the gut microbiota profile of participants colonised with RK as compared to participants who only carry antibiotic susceptible enterobacteria in the gut. It is beyond the scope of our feasibility study to enrol a sample of persons that is representative of the wider population, or to account for sample size and power calculations that would allow for characterisation of statistically meaningful associations.

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

• Study Contact: Name: Olga Tosas, phD DVM; Phone Number: +442071888163; Email: olga.tosas@gstt.nhs.uk
• Study Contact Backup: Name: Jonathan Edgeworth, MBBS; Phone Number: +4420171887188; Email: jonathan.edgeworth@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: Olga Tosas, PhD; Phone Number: +442071888163; Email: olga.tosas@gstt.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Any adult hospitalized patient at Guy's and St Thomas' Foundation Trust who carries resistant gram negative bacteria on a screening or clinical sample

Description

Inclusion Criteria:

• Study A ('Mapping'): Retrospective data collection from the hospital laboratory information system on patients diagnosed with infection and/or colonisation by relevant gram negative bacteria and antibiotic resistance profile.

• Study B ('Tracking'):

  • Inclusion criteria for index participants are being at least 16 years of age, able to consent for themselves and to communicate in English at the time of being invited to participate in the study. Inclusion criteria for index participants in the RK group include gut colonisation by Klebsiella spp. with resistance to carbapenems or third generation cephalosporins, as demonstrated by the analysis of a stool sample provided at baseline. Inclusion criteria for index participants in the control group, are lack of colonisation by bacteria resistant to third generation cephalosporins or carbapenems, as demonstrated by the analysis of a stool sample provided at baseline and at 6 months after discharge from hospital.
  • Inclusion criteria for network participants are persons of any age who are sharing the household with an index participant in the RK group and who meet the definition of usual household resident.

Exclusion Criteria:

• Study A ('Mapping'): Exclusion criteria include data from penitentiary patients.

Study B ('Tracking'):

• Exclusion criteria for index participants are those not meeting the inclusion criteria, penitentiary patients, those with no fixed adobe or not residing in a household space as defined in this study, and those living alone.
• Exclusion criteria for network participants are those not meeting the inclusion criteria, those meeting exclusion criteria as defined for index participants, those who are adults unable to consent for themselves, and those who are not able to communicate in English.
• Exclusion criteria for households are those not meeting the inclusion criteria, those where the index participant resides alone (i.e. no other usual residents in the household), those were at least one resident is not eligible for inclusion (including where a resident does not meet the definition of usual resident), those where at least one usual resident does not want to take part in the study, and those which are more than one hour commute from the study site

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
RK Group; participants colonised with Klebsiella spp. resistant to either 3GC or carbapenems (RK cohort of index carriers of Resistant Klebsiella)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transmission of resistant gram negative bacteria from index participants and network participants	To measure household transmission between index participants and household members of resistant bacteria through collection of stool samples.	6 months
Length of Gut Carriage of resistant gram negative bacteria in index participants	Measure how long resistant gram negative bacteria persist in the stool by measuring carriage of bacteria in longitudinal stool samples	6 months

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Jonathan Edgeworth, MBBS, Guy's and St Thomas NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: January 18, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimate): January 28, 2016

Study Record Updates

• Last Update Posted (Estimate): November 28, 2016
• Last Update Submitted That Met QC Criteria: November 24, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: carbapenem resistance; bacterial carriage; multi-drug resistant gram negative bacteria
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Gram-Negative Bacterial Infections
• Other Study ID Numbers: RJ115/N354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO