Staphylococcus Aureus Caught in Action at the Site of Infection

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Staphylococcus (S.) Aureus Infection

Intervention / Treatment
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* Other: data collection
* Diagnostic Test: blood draw
* Diagnostic Test: nose swabs
* Diagnostic Test: Intraoperative tissue samples


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with S. aureus infection<br> | Other: data collection<br>* 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.<br>Diagnostic Test: blood draw<br>* 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.<br>Diagnostic Test: nose swabs<br>* 2 nose swabs will be taken in the patient. 1 nose swab will be performed in the healthy proband.<br>Diagnostic Test: Intraoperative tissue samples<br>* Intraoperative tissue samples from the site of infection during surgery will be taken in the patient.<br>|
| healthy participants<br> | Other: data collection<br>* 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.<br>Diagnostic Test: blood draw<br>* 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.<br>Diagnostic Test: nose swabs<br>* 2 nose swabs will be taken in the patient. 1 nose swab will be performed in the healthy proband.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic therapy, virulence factor adaptations, resistance development, genomic alterations of S. aureus