Clinical trial NCT03465683: Transmission of ESBL-producing Enterobacteriaceae
Official title: Transmission of ESBL-producing Enterobacteriaceae and Their Mobile Genetic Elements-identification of Sources by Whole Genome Sequencing
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hospital Acquired Infection
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2018-03-14
Enrollment: 2000
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: out and inpatients from University Hospital Basle

Brief summary: The aim of this research project is to investigate the transmission of ESBL-producing Enterobacteriaceae on both, the level of bacterial strains and mobile genetic elements, and to determine the source of hospital-acquired infections.

Detailed description: Background and aim The most common bacterial pathogens in humans include several species of the family of Enterobacteriaceae. Many of them have now become resistant to antibiotics, i.e.extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae (PE). For a long time it was thought that transmission in hospitals was the main factor driving their rapid spread. More recently, though, ESBL-PE have also been found on food and in waste water. These sources are also likely to play an important role in entertaining transmission.

Investigator's aim is to identify transmission chains of ESBL-PE in the Basel urban region, using the latest whole genome sequencing methodologies allowing to determine relatedness of strains with the highest possible resolution, taking into account sources both within and outside hospitals.

Hypothesis The finding of few genetically-related clusters of ESBL-PE with an epidemiological link to hospital contacts would suggest relevant transmission in our healthcare setting. In contrast, the finding of many genetically-distinct clusters of ESBL-PE without epidemiological links to the hospital, would question the importance of hospital-wide transmission in sustaining the ESBL epidemic. This distinction is critical for deriving effective prevention and control recommendations.

Design, setting and patients Whole genome sequencing will be performed on representative ESBL-strains collected from January 2003 to December 2019 at the University Hospital Basel. The epidemiological relationships between patients with genetically related strains of ESBL-PE will be assessed.

From June 2017 to December 2019, whole genome sequencing will in addition be performed on ESBL-strains identified from representative samples from the wastewater system of both the hospital and the city of Basel as well as representative foodstuff samples collected from both the hospital and the city of Basel. The epidemiological relationships between patients, as well as environmental samples with genetically related strains of ESBL-PE and cases with genetically related plasmids carrying the respective ESBL genes will be assessed.

Methods, planned analysis and sample size To identify transmission events we will employ whole genome sequencing with Illumina technology, which is established and International Standards Organization (ISO)-accredited at the Clinical Microbiology Department at the University Hospital. The proportion of infection/colonization with genetically related isolates of ESBL-producing Enterobacteriaceae of the overall infection/colonization rate will be determined. All phylogenies will be inferred using BEAST v2.046 employing our previously developed tool for quantifying transmission rates. Overall, 2000 isolates from patient's samples and 1000 isolates from food and wastewater samples will be analysed.

Eligibility criteria: Inclusion Criteria:

* aged above 1 year
* proven ESBL-PE carriage from any specimens obtained by routine clinical practice out and inpatients from University Hospital Basle from January 1st until December 31st 2019

Exclusion Criteria:

* not meeting inclusion criteria

Primary outcomes:
measure: Infection/colonization proportion
timeFrame: through study completion, an average of 45months
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Switzerland, Division of Infecteous Disease and Hospital Epidemiology
Study officials:
affiliation: Division of Infectious Disease and Hopital Epidemiology, University Hospital Basle
name: Sarah Tschudin-Sutter, PD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aguilar-Bultet L, Bagutti C, Egli A, Alt M, Maurer Pekerman L, Schindler R, Furger R, Eichenberger L, Roloff T, Steffen I, Huebner P, Stadler T, Tschudin-Sutter S. Identification of a Cluster of Extended-spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Sequence Type 101 Isolated From Food and Humans. Clin Infect Dis. 2021 Jul 15;73(2):332-335. doi: 10.1093/cid/ciaa1164.