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

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

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.

Study Overview

• Status: Unknown
• Conditions: Antibiotic Resistant Infection; VRE Infection
• Intervention / Treatment: Other: Rectal swabs - microbiological analysis; Other: Examination of patient room

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 170

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50931
      • Recruiting
      • University Hospital of Cologne
      • Contact: Jörg Janne Vehreschild, MD; Email: joerg.vehreschild@uk-koeln.de

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

The selection of patients to be included in Part 1 of the AEGON study is based on the risk stratification for the nosocomial acquisition of VREf performed in the CONTROL study.

It is planned to include a total of 150 patients from the participating study centers in Part 1. Based on the results of the CONTROL study, it can be assumed that within the selected target group in approx. 11% there is already an VREf colonisation by direct culture at admission and in 15% of the cases (22 of 150 patients) a nosocomial acquisition of VREf by direct culture (see method part) can be determined. Patients with VREcolonization detected at admission are excluded from the study.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: VRE negative at admission; 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; Microbial analyses will be performed from the rectal swabs obtained.
Cohort 2: VRE positive at admission; 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; Microbial analyses will be performed from the rectal swabs obtained.; Other: Examination of patient room; Only performed for cohort 2

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University Hospital of Cologne
• Collaborators: Universitätsklinikum Hamburg-Eppendorf; University of Freiburg; University Hospital Lübeck
• Investigators: Principal Investigator: Jörg Janne Vehreschild, Prof. Dr. med, University Hospital of Cologne; Principal Investigator: Maria J.G.T. Vehreschild, Prof. Dr. med, University Hospital of Cologne

Publications and helpful links

General Publications

• Gastmeier P, Schroder C, Behnke M, Meyer E, Geffers C. Dramatic increase in vancomycin-resistant enterococci in Germany. J Antimicrob Chemother. 2014 Jun;69(6):1660-4. doi: 10.1093/jac/dku035. Epub 2014 Mar 9.
• Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fatkenheuer G, Wisplinghoff H, Seifert H, Vehreschild MJ. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection. 2012 Dec;40(6):613-9. doi: 10.1007/s15010-012-0269-y. Epub 2012 Jun 5.
• Vehreschild MJGT, Haverkamp M, Biehl LM, Lemmen S, Fatkenheuer G. Vancomycin-resistant enterococci (VRE): a reason to isolate? Infection. 2019 Feb;47(1):7-11. doi: 10.1007/s15010-018-1202-9. Epub 2018 Sep 3.
• Biehl LM, Higgins P, Wille T, Peter K, Hamprecht A, Peter S, Dorfel D, Vogel W, Hafner H, Lemmen S, Panse J, Rohde H, Klupp EM, Schafhausen P, Imirzalioglu C, Falgenhauer L, Salmanton-Garcia J, Stecher M, Vehreschild JJ, Seifert H, Vehreschild MJGT. Impact of single-room contact precautions on hospital-acquisition and transmission of multidrug-resistant Escherichia coli: a prospective multicentre cohort study in haematological and oncological wards. Clin Microbiol Infect. 2019 Aug;25(8):1013-1020. doi: 10.1016/j.cmi.2018.12.029. Epub 2019 Jan 12.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: VRE; Antimicrobial Stewardship; Infection Control Measures
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 19-1325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No