Comparison of Pulsed-field Gel Electrophoresis and Whole Genome Sequencing to Determine Transmission Rate of ESBL-producing E.Coli

Analysis Transmission Rate Clinical Trial

— PFGE-WGS  

Official title:

Comparison of Pulsed-field Gel Electrophoresis and Whole Genome Sequencing to Determine Transmission Rate of ESBL-producing E.Coli

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04323553
• Other study ID #: 2020-00188
• Status: Enrolling by invitation
• Start date: March 6, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this quality control study is to compare two different techniques to determine ESBL-producing E.coli transmission.

Description:

Pulse-field gel electrophoresis (PFGE) was considered the reference standard to determine transmission events of extended-spectrum Beta-Lactamase (ESBL) producing E.coli . However, this technique lacks the resolution to differentiate closely related strains, which is needed to identify ESBL-transmission. Furthermore, PFGE is not able to distinguish mobile genetic elements. In contrast, whole genome sequencing (WGS) allows the identification of single-nucleotide polymorphisms (SNPs) that differentiate bacterial strains and mobile genetic elements, such as plasmids at the highest possible resolution, therefore enabling investigation of their relatedness by phylogenetic analyses and ultimately detailed exploration of transmission pathways. As WGS is now readily available and affordable, the investigators aim to reinvestigate transmission events in the 24 index-contact patient-pairs identified after cessation of contact precautions by reassessing the genetic relatedness of both strains and mobile genetic elements by sequencing all 48 recovered ESBL- E.coli strains.

The investigators hypothesize that the number of transmission events as defined by transmission of ESBL-producing E. coli strains may have been overestimated by PFGE as compared to WGS, as PFGE lacks the resolution to differentiate closely related strains. However, transmission of mobile genetic elements may have been missed by PFGE as this technology is not able to identify the genetic relatedness of plasmids, genes and other mobile genetic elements. Thus WGS may reveal additional transmission events defined as the transmission of mobile genetic elements.

Different sequencing approaches may yield different results in terms of detection of transmission events.

The investigators hypothesize that short-read sequencing may suffice to reliably detect relatedness of strains but that additional long-read sequencing approaches are needed to detect transmission of mobile genetic elements.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 48
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• The patient population is defined as the 24 contact-index patient pairs identified during screening of contact patients after cessation of contact precautions as part of a quality control, performed from June 2012 to December 2013 at the University Hospital Basel and from January 2012 to December 2013 at the FELIX PLATTER-Hospital.

Exclusion Criteria:

• Patients not meeting the above mentioned inclusion criteria.

Related Conditions & MeSH terms

• Analysis Transmission Rate

Intervention

Diagnostic Test:
• Pulsed-field gel electrophoresis and whole genome sequencing
Comparison of the two different techniques

Other:
• Data collection
Demographic data (age, gender, hospital admission and discharge date, rooms and wards with dates of admission and discharge, hospitalization prior to current hospital stay, discharge destination, outcome, cause of death, travel history, recent hospitalization in an ESBL-high burden region, admission from another healthcare facility, admission from a long-term care facility, occupational or household contact to animals) Clinical data (date of diagnosis of ESBL-producing E. coli carriage, type of infection/colonization with ESBL- producing E. coli, comorbidities, Charlson Comorbidity Index, infectious diseases after detection of ESBL-PE, active open wounds, indwelling vascular devices, urinary catheterization) Treatment data (Immunosuppression, antibiotic therapy, concomitant medication and surgical therapy prior to and during hospital stay) Microbiological data

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Division of Infectious Diseases and Hospital Epidemiology	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of transmission events as determined by WGS	Transmission events will be categorized into transmission of strains and transmission of mobile genetic elements. The number of transmission events as determined by WGS will be compared to the number of transmission events as determined by PFGE. Patient-related characteristics and exposures will be compared between patients with and without transmission events.	January 2012- December 2020