Staphylococcus Aureus Caught in Action at the Site of Infection (PROSA)

A Single Centre, Unblinded, Prospective Cohort Study Identifying Pathogen Adaptations in Patients Suffering From Invasive S. Aureus Infection Compared to Colonized, Healthy Individuals

This study is to obtain a comprehensive view of S. aureus adaptations in the infected human host and (i) to improve the understanding of the interface between antibiotic therapy, resistance development and virulence factor adaptation in S. aureus infected patients, and (ii) to adapt these findings into a more sustainable use of antimicrobials for therapy.

Study Overview

• Status: Completed
• Conditions: Staphylococcus (S.) Aureus Infection
• Intervention / Treatment: Other: data collection; Diagnostic test: blood draw; Diagnostic test: nose swabs; Diagnostic test: Intraoperative tissue samples

Detailed Description

Staphylococcus (S.) aureus is notorious for its ability to develop resistance. This study is to obtain a comprehensive view of S. aureus adaptations in the infected human host and (i) to improve the understanding of the interface between antibiotic therapy, resistance development and virulence factor adaptation in S. aureus infected patients, and (ii) to adapt these findings into a more sustainable use of antimicrobials for therapy.

Patients with S. aureus infections who will routinely undergo diagnostic and surgical procedures will be identified. Intraoperative samples from the site of infection during surgery will be taken. Additionally, two blood drawing events (22.5ml in total) will be performed and nose swabs will be taken. The biological material will be analysed. This project will be the first to study different phenotypes of invasive S. aureus directly from its environment in vivo.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Hospitalized patients with probable or proven S. aureus infection will be screened at the University Hospital of Basel. Patients with confirmed S. aureus infection who correspond to the eligibility criteria will be asked to participate in the research project.

Healthy volunteers who correspond to the eligibility criteria will be asked to participate in the research project and recruited by oral communication from the institutions Biozentrum, University Hospital Basel, and University of Basel.

Description

Inclusion criteria for patients:

• In collaboration with the orthopedic surgeons, patients with probable or proven S. aureus infections will be identified who will routinely undergo diagnostic and surgical procedures:

Inclusion criteria for healthy participants:

• Healthy control group should be generally well-being

Exclusion criteria for patients and for healthy participants:

• Pregnancy: Pregnant or lactating women will be excluded (urinary pregnancy test will be performed in women of childbearing age)
• General health condition: Current or recurrent disease that could cause complications that may affect the study or may set the patient at risk
• Diseases/ Illness: Psychiatric or other mental disorders which in the opinion of the investigator may probably affect the full understanding of the study (including signs of dementia)
• Language: Insufficient knowledge of german language to understand the procedure and rationale of the research question
• Vulnerability: Individuals whose willingness to volunteer in the research project may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, such as members of a group with a direct hierarchical structure (refer to ICH Guidelines E6 (R1) for GCP, 1.61)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
healthy participants	Other: data collection; Health-related personal data such as year of birth, sex, Body Mass Index (BMI), infection classification, concomitant infections, comorbidities according to medical chart, standard diagnostic markers (CRP, blood differential plots, creatinine, ...), medication, treatment start, treatment end and discharge from hospital will be collected.; Diagnostic test: blood draw; 2 blood drawing events (in total 22.5 ml) will be performed in the patient. 1 blood drawing events will be performed in the healthy proband.; Diagnostic test: nose swabs; 2 nose swabs will be taken in the patient. 1 nose swab will be performed in the healthy proband.
Patients with S. aureus infection	Other: data collection; Health-related personal data such as year of birth, sex, Body Mass Index (BMI), infection classification, concomitant infections, comorbidities according to medical chart, standard diagnostic markers (CRP, blood differential plots, creatinine, ...), medication, treatment start, treatment end and discharge from hospital will be collected.; Diagnostic test: blood draw; 2 blood drawing events (in total 22.5 ml) will be performed in the patient. 1 blood drawing events will be performed in the healthy proband.; Diagnostic test: nose swabs; 2 nose swabs will be taken in the patient. 1 nose swab will be performed in the healthy proband.; Diagnostic test: Intraoperative tissue samples; Intraoperative tissue samples from the site of infection during surgery will be taken in the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of virulence factors of S. aureus (derived from patient's samples (tissue, nose swab)) by combining highly sensitive mass spectrometry with whole genome sequencing.	Expression of virulence factors of S. aureus (derived from patient's samples (tissue, nose swab)) by combining highly sensitive mass spectrometry with whole genome sequencing. There is neither a primary nor a secondary endpoint in this research project.	Project duration for each patient will be two days
Antibiotics concentration	Antibiotics concentration with chromatography methods (in tissue, blood)	Project duration for each patient will be two days
Expression of genomic alterations of S. aureus (derived from patient's samples (tissue, nose swab)) by combining highly sensitive mass spectrometry with whole genome sequencing.	Expression of genomic alterations of S. aureus (derived from patient's samples (tissue, nose swab)) by combining highly sensitive mass spectrometry with whole genome sequencing. There is neither a primary nor a secondary endpoint in this research project.	Project duration for each patient will be two days

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Nina Khanna, PD Dr. med., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2017
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: June 2, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: antibiotic therapy; virulence factor adaptations; resistance development; genomic alterations of S. aureus
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 2017-00793; me20Khanna

Drug and device information, study documents

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