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

Patients at High Risk of Antibacterial Treatment Upon Admission Clinical Trial

— PILGRIM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03765528
• Other study ID #: PILGRIM
• Status: Recruiting
• Start date: January 1, 2019
• Est. completion date: July 31, 2022

Study information

• Verified date: July 2020
• Source: University Hospital of Cologne
• Contact: Jörg Janne Vehreschild, MD
• Phone: +49227478
• Email: joerg.vehreschild[@]uk-koeln.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Infection
• Patients at High Risk of Antibacterial Treatment Upon Admission

Locations

Country	Name	City	State
Germany	University Hospital of Cologne	Cologne	NRW

Sponsors (10)

Lead Sponsor	Collaborator
University Hospital of Cologne	Haukeland University Hospital, Helse Stavanger HF, Karolinska Institutet, McGill University Health Centre/Research Institute of the McGill University Health Centre, Rabin Medical Center, University Hospital of North Norway, University Hospital, Akershus, University Hospital, Frankfurt, University of Latvia

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of inappropriate antibacterial prescription on intestinal microbiota domination by healthcare associated pathogens	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.	up to 6 - 36 weeks
Secondary	Time-point of Intestinal Colonization	Determination of the rate of in-hospital vs. pre-admission intestinal colonization with EPE, VRE, and/or C. difficile measured by analysing stool samples.	Baseline and up to 6 - 36 weeks
Secondary	Time-point of Intestinal Domination	Determination of the rate of in-hospital vs. pre-admission intestinal domination with EPE, VRE, and/or C. difficile measured by analysing stool samples.	Baseline and up to 6 - 36 weeks
Secondary	Inter-rater reliability of AMS specialists	Determination of the inter-rater reliability of interdisciplinary AMS specialists rating antibacterial prescription appropriateness.	After complete documentation of each patient case (follow-up for 6-36 weeks) followed by completed ratings of AMS specialists
Secondary	Rationale for antibacterial prescription habits assessed by performing qualitative interviews with prescribing physicians	Identification of behavioral determinants and knowledge gaps leading to inappropriate antibacterial prescriptions by interviewing approximately 50 prescribing physicians.	After complete documentation of patient case (follow-up for 6-36 weeks) through study completion
Secondary	Correlation of prescription and AMS implementation	Assessment of the correlation of appropriate antibacterial prescription with quality indicators of AMS implementation	Baseline, 12 months, 24 months
Secondary	Identification of risk factors responsible for disrupting the intestinal microbiota	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.	Baseline and weekly up to 6 - 36 weeks of follow-up