Clinical trial NCT04323553: Comparison of Pulsed-field Gel Electrophoresis and Whole Genome Sequencing to Determine Transmission Rate of ESBL-producing E.Coli
Official title: Comparison of Pulsed-field Gel Electrophoresis and Whole Genome Sequencing to Determine Transmission Rate of ESBL-producing E.Coli
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Analysis Transmission Rate
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 43
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The patient population is defined as the 24 contact-index patient pairs identified during screening of contact patients after cessation of contact precautions during June 2012 to December 2013 at the University Hospital Basel and from January 2012 to December 2013 at the FELIX PLATTER-Hospital.

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of transmission events as determined by WGS
timeFrame: January 2012- December 2020
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Infectious Diseases and Hospital Epidemiology
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Sarah Tschudin Sutter, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: