NExt-Generation Sequencing and Cell Culture-based Characterization of S. Aureus in Infective Endocarditis (NESSIE)

February 3, 2020 updated by: Mahmoud A. Diab, Jena University Hospital

Infective endocarditis is a deadly disease with a mortality rate between 20 and 40%. Antibiotic therapy is of utmost importance. It is primarily guided by microbial results from positive blood culture. However, culture-based microbiological diagnostic can identify the species, but not the strain or the genotypic characteristics of a pathogen. Identifying the strain can be of utmost clinical significance. S. aureus is the most common causative organism of IE worldwide (16%-32%). This pathogen causes massive valve destruction and abscesses, which is strongly dependent on the expression of virulence factors that vary between different S. aureus strains.

Functional characterization of S. aureus and determination of virulence factors can currently be achieved through cell culture-based assays (CCBA). However, these tests are very time consuming and cannot be performed as routine clinical diagnostics. Next Generation Sequencing (NSG) has the potential to identify the genotypic characteristics of the pathogen, which is important to determine its virulent potential.

The aim of this study is to evaluate the possible utilization of NGS in the prediction of virulence factors of S. aureus and to compare it to the virulence factors determined using CCBA.

Hopefully, by comparing the NGS and CCBA, the investigators will get a faster way of determining the possible virulence factors. The NGS method can be further utilized to describe the prevalence of different strains of bacteria in infected valve tissue and blood culture samples. The collected data will serve as a basis for further evaluation of the potentials of NGS-based Diagnosis of IE, as well as a comparison between NGS-guided antibiotic treatment and the standard of care antibiotic treatment.

Study Overview

Detailed Description

The ability of the Staphylococcus aureus to produce massive valve destruction as well as abscesses and to switch from acute to chronic infection and vice versa is a significant issue in the modern treatment of infective endocarditis. Furthermore, the ability to produce different virulence factors to evade the immune defense mechanisms proves the treatment more difficult. Another conundrum is the proof of different S. aureus strains isolated from Blood culture samples and infected valve samples. This makes a possible treatment of S. aureus-based endocarditis more difficult than expected.

Isolation of Bacteria in the Blood culture samples can take much time (3-14 days), and Cell Culture-based assays (CCBA) are not regularly implemented as a diagnostic procedure. CCBA is not regularly used in the clinical setting due to the time consumption and high cost. The significance of the CCBA method lies in the determination of the possible virulence factors. Utilizing the Next Generation Sequence (NGS) method, it might be possible to gain this information about the culprit microorganism faster and to identify the different strains and virulence factors.

To date, such correlations between genetic information about virulence factors gained by NGS and phenotypic information obtained by cell culture-based assays have not yet been performed.If proven, the NGE based analysis of the pathogens and their phenotypical behavior could guide antimicrobial therapy and make it individualized. Blood culture and infected tissue valve samples will be examined using the NGS and CCBA. The investigators aim to compare the differences in virulence factor results in these two methods, to characterize the prevalence of different strains of S. aureus in the blood culture and valve samples and to evaluate the possible potentials of NGS-based diagnosis of IE and to compare the effects of the NGS-guided antimicrobial therapy to the standard of care therapy.

Study Type

Observational

Enrollment (Anticipated)

10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

patients with the diagnosis infective endocarditis and indication for heart surgery on a heart valve

Description

Inclusion Criteria:

  • patients with the diagnosis infective endocarditis and indication for heart surgery on a heart valve
  • signed informed consent
  • age ≥18 years
  • pathogens (S. aureus) can be isolated from blood culture AND from the removed valve tissue

Exclusion Criteria:

  • S. aureus can not be isolated from removed valve tissue

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
biofilm growth
Time Frame: through study completion (about 1 year)
ability of S. aureus strains isolated from the blood and heart tissue of included patients to build a biofilm
through study completion (about 1 year)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
invasion characteristics
Time Frame: through study completion (about 1 year)
characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients to invade other cells (host cell invasion; persistence in host cells; tests will be conducted in cell culture)
through study completion (about 1 year)
adhesion characteristics
Time Frame: through study completion (about 1 year)
characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients to adhere to other human cells (important information regarding the ability to attach to heart tissue; test will be conducted in cell culture)
through study completion (about 1 year)
toxine production
Time Frame: through study completion (about 1 year)
characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients regarding production of toxins which will lead to information about induction of inflammation processes and induction of host cell death
through study completion (about 1 year)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Mahmoud A Diab, Dr. med., Jena University Hospital, Clinic for Cardiac and Thoracic Surgery

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2019

Primary Completion (Anticipated)

February 28, 2020

Study Completion (Anticipated)

July 31, 2020

Study Registration Dates

First Submitted

September 5, 2019

First Submitted That Met QC Criteria

February 3, 2020

First Posted (Actual)

February 6, 2020

Study Record Updates

Last Update Posted (Actual)

February 6, 2020

Last Update Submitted That Met QC Criteria

February 3, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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