Assessing the Impact of Antimicrobial Exposure and Infection Control Measures on the Spread of VRE

Study Overview
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Brief Summary
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The AEGON study is a German multicenter, prospective observational study. The study consists of two parts, which are carried out at all participating study sites and include two different patient cohorts. Part 1 focuses on the collection and analysis of rectal swabs from newly admitted VREf-negative patients at high risk of nosocomial VREf acquisition. Moreover, patients included into this part of the study will undergo in-depth documentation of clinical data if an antibiotic therapy is administered. Initiated antibiotic therapies will then be assessed by an AMS board (Antimicrobial Stewardship Board). In Part 2, environmental investigations will be performed in newly occupied single rooms of previously known VREf-positive patients. In addition, rectal swabs will be collected and data on antibiotic exposure of these patients will be documented in order to correlate the VRE contamination burden of surfaces with the intestinal VREf-load and antibiotic exposure.

Detailed Description
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Current studies show that Vancomycin-resistant Enterococci (VRE) have become increasingly widespread throughout Germany in recent years, especially E. faecium (VREf). Healthy individuals can come into contact with VREf in various ways, for example via the food chain, contaminated drinking water or animal contacts. A possibly caused low-grade colonisation of the gastrointestinal tract with VREf (so-called low-level colonisation) can remain undetected during hospital admission using routine screening methods. The AEGON study, based on the use of state-of-the-art molecular diagnostics and comprehensive clinical data collection, will provide a detailed analysis of the factors involved in the rapid spread of VREf. In addition, diagnostic detection limits of common screening methods are determined by the use of additional diagnostics such as enrichment culture or molecular VREf detection. The study is a German multicenter, prospective observational study and consists of two parts, which are carried out at all participating study sites and include two different patient cohorts. Part 1 focuses on the collection and analysis of rectal swabs from newly admitted VRE-negative patients at high risk of nosocomial VREf acquisition. Moreover, patients included into this part of the study will undergo in-depth documentation of clinical data if an antibiotic therapy is administered. Initiated antibiotic therapies will then be assessed by an AMS board. In Part 2, environmental investigations will be performed in newly occupied single rooms of previously known VREf-positive patients. In addition, rectal swabs will be collected and data on antibiotic exposure of these patients will be documented in order to correlate the VRE contamination burden of surfaces with the intestinal VREf-load and antibiotic exposure. The AEGON study, based on the use of state-of-the-art molecular diagnostics and comprehensive clinical data collection, will provide a detailed analysis of the factors involved in the rapid spread of VREf. In addition, diagnostic detection limits of common screening methods are determined by the use of additional diagnostics such as enrichment culture or molecular VREf detection.

Official Title
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Assessing the Impact of Antimicrobial Exposure and Infection Control Measures on the Spread of Vancomycin-resistant Enterococcus Faecium (VREf) - A Prospective Study

Conditions
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VRE Infection, Antibiotic Resistant Infection

Intervention / Treatment
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* Other: Rectal swabs - microbiological analysis
* Other: Examination of patient room


Participation Criteria
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Eligibility Criteria
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Part 1 Inclusion Criteria: ≥ 18 years Patients with malignant primary disease and current inpatient admission to a normal ward with expected inpatient stay of at least 15 days High risk of exposure to antibiotics during the stay Written informed consent of the patient after clarification has been given Exclusion Criteria: Already known current or documented past colonisation or infection by VRE Simultaneous participation in other studies is only an exclusion criterion if the other study explicitly excludes participation in observational studies or if the other study complicates the interpretation of the endpoints of AEGON (e.g. double-blind study on antibiotic use).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: VRE negative at admission<br>150 patients meeting the following inclusion criteria: ≥ 18 years Patients with malignant primary disease and current inpatient admission to a normal ward with expected inpatient stay of at least 15 days High risk of exposure to antibiotics during the stay Written informed consent of the patient after clarification has been given Exclusion criteria: Already known current or documented past colonisation or infection by VRE Simultaneous participation in other studies is only an exclusion criterion if the other study explicitly excludes participation in observational studies or if the other study complicates the interpretation of the endpoints of AEGON (e.g. double-blind study on antibiotic use). | Other: Rectal swabs - microbiological analysis<br>* Microbial analyses will be performed from the rectal swabs obtained.<br>|
| Cohort 2: VRE positive at admission<br>A total 20 known VREf-positive patients meeting the following inclusion criteria: Intestinal VREf colonization already known at the time of admission (e.g. based on examinations during previous stays or in external facilities) Accommodation in a single room or alternatively multi-bed room with single occupancy on standard wards Expected stay of at least 7 days | Other: Rectal swabs - microbiological analysis<br>* Microbial analyses will be performed from the rectal swabs obtained.<br>Other: Examination of patient room<br>* Only performed for cohort 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VREf - Intestinal microbiota | Primary Outcome for Cohort 1: Rate of VREf intestinal colonization detected by enrichment culture or specific PCR at time of uptake not detected by standard culture methods | Baseline | 
| VREf - Patient rooms | Primary Outcome for Cohort 2: Description of the spread of VREf in single rooms newly enrolled in known VREf-positive patients | Change from baseline spread to spread at 10 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard culture VREf detection | Cohort 1: Quantitative detection limit of standard culture methods for VREf detection compared to enrichment culture and qPCR (quantitative polymerase chain reaction) | baseline and every week up to 10 weeks max. | 
| Antibiotics | Cohort 1: Identification of antibiotic classes that increase the risk of clonal expansion and subsequent domination by VREf. Domination by VREf is defined as the combination of cultural VREf detection from a sample and 16S rRNA (16S ribosomal ribonucleic acid) sequencing of the relative frequency of the Enterococcus genus over 30% as the most abundant genus in the sample. | baseline and every week up to 10 weeks max. | 
| Inadequately administered antibiotics | Cohort 1: Proportion of inadequately administered antibiotics, defined as unnecessary, too long, too broad or too high doses in patients who develop VREf domination (see definition above) compared to patients without VREf acquisition and patients with VREf acquisition but without domination. | baseline and every week up to 10 weeks max. | 
| Adequate antibiotic | Cohort 1: Rate of patients with no or adequate antibiotic therapy compared to patients with inadequate antibiotic therapy who develop a new colonization with VREf during the stay | baseline and every week up to 10 weeks max. | 
| Influence of antibiotic exposure duration | Cohort 1: Influence of antibiotic exposure duration on microbiota | baseline and every week up to 10 weeks max. | 
| Influence of antibiotic class | Cohort 1: Influence of antibiotic class on microbiota | baseline and every week up to 10 weeks max. | 
| VREf contamination | Cohort 2: Identification of high risk objects and surfaces for VREf contamination in patient rooms with known VREf-positive patients | baseline at least every 72 hours up to max of 20 days. | 
| Correlation of the antibiotic exposure | Cohort 2: Correlation of the antibiotic exposure of already known VREf-positive patients with the contamination load of objects and surfaces in the corresponding patient room. | baseline at least every 72 hours up to max of 20 days. | 
| Contamination load of objects | Cohort 2: Correlation of the relative proportion of enterococci in intestinal microbiota with the contamination load of objects and surfaces in the associated patient room | baseline at least every 72 hours up to max of 20 days. | 
| Cleaning quality | Cohort 2: Correlation of cleaning quality with the contamination load of VREf on objects and surfaces in rooms of known VRE-positive patients | baseline at least every 72 hours up to max of 20 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VRE, Infection Control Measures, Antimicrobial Stewardship