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Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens (PILGRIM)

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ClinicalTrials.gov Identifier: NCT03765528
Recruitment Status : Not yet recruiting
First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Collaborators:
University Hospital of North Norway
Karolinska Institutet
Rabin Medical Center
University of Latvia
McGill University Health Center
Haukeland University Hospital
University Hospital, Akershus
Helse Stavanger HF
University Hospital, Frankfurt
Information provided by (Responsible Party):
Dr. med. Jörg Janne Vehreschild, University Hospital of Cologne

Brief Summary:
Extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), vancomycin-resistant enterococci (VRE) and Clostridium difficile have become a major threat to hospitalised patients worldwide. We hypothesize that receiving inappropriate antibacterial treatment places patients at high risk of intestinal domination and subsequent infection by these bacteria. Further analyses will address cost-effectiveness of specific interventions, behavioural analyses of the decision process leading to inappropriate antibacterial treatment, and the rate of undetected colonization with EPE/VRE/C. difficile on admission.

Condition or disease
Patients at High Risk of Antibacterial Treatment Upon Admission

Detailed Description:

The prevalence of antimicrobial resistant pathogens has dramatically increased among hospitalised patients worldwide. While various management strategies have effectively reduced the burden caused by methicillin-resistant Staphylococcus aureus, resistant pathogens with a preference towards intestinal colonization are currently on the rise. E.g., vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE) now constitute a significant threat to hospitalised patients worldwide, as infections due to these organisms require prolonged treatments and result in inferior outcomes. Similarly, the burden of disease caused by Clostridium difficile infection (CDI), the main cause of healthcare-associated infectious diarrhoea, has increased driven by the emergence of hypervirulent strains such as ribotypes 027 and 078. Molecular studies have demonstrated that increased population-wide exposure to broad-spectrum antibacterials is a crucial step in the initiation of outbreaks by selection and expansion of resistant C. difficile.

This is a comprehensive, multinational, multi-centre clinical study aiming to assess the impact of inappropriate antibacterial prescription on intestinal domination by EPE or VRE or infection with C. difficile. To achieve this goal, the study will closely follow the progression from first acquisition of drug-resistant organisms to infection with these bacteria at an individual patient level.

In this study, we will establish the sequence and factors involved in acquisition, colonization, selective pressure, bacterial overgrowth/domination/ and infection for EPE, VRE and C. difficile. We hypothesize that IC (Infection Control; prevention of pathogen acquisition) and AMS (Antimicrobial Stewardship; prevention of clonal expansion) measures leading to a higher share of appropriate anti-infective use are effective strategies to prevent this development. The study programme will allow an accurate estimation of the preventable share of healthcare-acquired colonization and infection by VRE, EPE, and C. difficile.

No direct interventions will be performed with study patients. Instead, study centres will assess quality indicators for implementation of IC and AMS measures by active observation and aggregation of data. Patients fulfilling all inclusion- and no exclusion criteria will be asked for their consent to be recruited prospectively into a cohort study. During the observational phase, participants will be monitored for receipt of antibacterial treatment and regular stool samples will be obtained and stored. An interdisciplinary, international AMS Board will comprehensively assess antibiotic treatment via review by a panel of experts. After the observation is completed, stool samples will be batch-tested for intestinal domination by the target pathogens of this study. Statistical analyses will be performed to investigate an association between inappropriate antibiotic use as opposed to appropriate or no antibiotic use and intestinal domination. If domination is detected, further analyses for phenotype, quantity, resistance, and molecular biology will be performed. Finally, the baseline sample will be tested for presence of the dominant species to understand the source of the pathogen, i.e. nosocomial versus outpatient acquisition.


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Study Type : Observational
Estimated Enrollment : 1500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens
Estimated Study Start Date : December 1, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Impact of inappropriate antibacterial prescription on intestinal microbiota domination by healthcare associated pathogens [ Time Frame: up to 6 - 36 weeks ]
    The differential impact of inappropriate antibacterial prescription compared to adequate or no antibacterial prescription on intestinal microbiota domination by EPE or VRE or infection with C. difficile measured by analysing stool samples.


Secondary Outcome Measures :
  1. Time-point of Intestinal Colonization [ Time Frame: Baseline and up to 6 - 36 weeks ]
    Determination of the rate of in-hospital vs. pre-admission intestinal colonization with EPE, VRE, and/or C. difficile measured by analysing stool samples.

  2. Time-point of Intestinal Domination [ Time Frame: Baseline and up to 6 - 36 weeks ]
    Determination of the rate of in-hospital vs. pre-admission intestinal domination with EPE, VRE, and/or C. difficile measured by analysing stool samples.

  3. Inter-rater reliability of AMS specialists [ Time Frame: After complete documentation of each patient case (follow-up for 6-36 weeks) followed by completed ratings of AMS specialists ]
    Determination of the inter-rater reliability of interdisciplinary AMS specialists rating antibacterial prescription appropriateness.

  4. Rationale for antibacterial prescription habits assessed by performing qualitative interviews with prescribing physicians [ Time Frame: After complete documentation of patient case (follow-up for 6-36 weeks) through study completion ]
    Identification of behavioral determinants and knowledge gaps leading to inappropriate antibacterial prescriptions by interviewing approximately 50 prescribing physicians.

  5. Correlation of prescription and AMS implementation [ Time Frame: Baseline, 12 months, 24 months ]
    Assessment of the correlation of appropriate antibacterial prescription with quality indicators of AMS implementation

  6. Identification of risk factors responsible for disrupting the intestinal microbiota [ Time Frame: Baseline and weekly up to 6 - 36 weeks of follow-up ]
    Identification of risk factors for colonization, intestinal domination, and infection by EPE, VRE and C. difficile, including comorbidities and drugs known to disrupt the intestinal microbiota, and high-risk bacterial clones prone to dominate the microbiota due to high fitness. Assessment by analysing stool samples and documented data.


Biospecimen Retention:   Samples Without DNA
Stool samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Hospitalized patients at high risk of receiving antibiotic treatment during their hospital stay will be screened for study eligibility.
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Planned treatment or high likelihood of any systemic antibacterial treatment except trimethoprim/sulfamethoxazole within the next 10 days for a duration of ≥ 5 days
  3. Patients able to provide a stool sample before or within 4 hours of receiving first antibiotic dosage
  4. Written informed consent provided prior to inclusion

Exclusion Criteria:

  1. Patients who have received courses of systemic antibacterials for 7 days or more within the past two months
  2. Patients having received any antibacterial compound other than trimethoprim/sulfamethoxazole within 14 days prior to study enrolment except first antibiotic dosage within 4 hours prior enrolment
  3. Patients with diarrhea at enrolment (≥3 unformed bowel movements within 24h)
  4. Patients with a stoma (jejunostomy, ileostomy, or colostomy) at time of inclusion
  5. Patients on enteral (tube fed or PEG) or parenteral nutrition
  6. Patient with any social or logistical condition which in the opinion of the investigator may interfere with the conduct of the study, such as incapacity to well understand, not willing to collaborate, or cannot easily be contacted after discharge
  7. Patients exclusively treated as outpatients without prior hospital admission
  8. Previous participation in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03765528


Contacts
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Contact: Jörg Janne Vehreschild, MD +49227478 ext 88794 joerg.vehreschild@uk-koeln.de
Contact: Annika Löhnert, MD annika.loehnert@uk-koeln.de

Locations
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Germany
University Hospital of Cologne
Cologne, NRW, Germany, 50931
Sponsors and Collaborators
University Hospital of Cologne
University Hospital of North Norway
Karolinska Institutet
Rabin Medical Center
University of Latvia
McGill University Health Center
Haukeland University Hospital
University Hospital, Akershus
Helse Stavanger HF
University Hospital, Frankfurt
Investigators
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Principal Investigator: Jörg Janne Vehreschild, MD University Hospital Cologne

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Responsible Party: Dr. med. Jörg Janne Vehreschild, Professor, University Hospital of Cologne
ClinicalTrials.gov Identifier: NCT03765528     History of Changes
Other Study ID Numbers: PILGRIM
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. med. Jörg Janne Vehreschild, University Hospital of Cologne:
Clostridium difficile
Extended-Spectrum β-Lactamase producing Enterobacteriaceae
Vancomycin-resistant enterococci
Antimicrobial resistance
Microbiome
Nosocomial infection
Antimicrobial Stewardship
Infection Control

Additional relevant MeSH terms:
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Infection
Anti-Infective Agents
Anti-Bacterial Agents