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Personalized Medicine in cardiovascular infections

English title Personalized Medicine in cardiovascular infections
Applicant Hasse Barbara
Number 184918
Funding scheme Project funding
Research institution Klinik für Infektionskrankheiten und Spitalhygiene Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Internal Medicine
Start/End 01.04.2019 - 31.12.2022
Approved amount 399'454.00
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All Disciplines (4)

Discipline
Internal Medicine
Clinical Cardiovascular Research
Surgery
Infectious Diseases

Keywords (7)

Fluorescence in situ hybridization; Infective endocarditis; Cardiovascular surgery; Broad range PCR; PET/CT; Vascular graft infection; Biofilm

Lay Summary (German)

Lead
Kardiovaskuläre Infektionen werden häufig von biofilmbildenden, langsam wachsenden Bakterien ausgelöst, wobei die bakterielle Persistenz die Heilung erschwert. In dem Projekt werden wir die Epidemiologie dieser Patienten studieren. Parallel dazu werden wir gleichzeitig die den Infekt verursachenden Bakterien im Detail untersuchen.
Lay summary

Inhalte und Ziele des Forschungsprojektes

Kardiovaskuläre Infektionen nehmen aufgrund der Alterung der Bevölkerung zu, und umfassen ein breites Spektrum von Infektionen die Herzklappen Blutgefässe, Gefässprothesen und intravaskuläre Geräte (Transkatheter-Aortenklappen, implantierbare Schrittmacher und Herzunterstützungsgeräte) betreffen. Herz-Kreislauf-Infektionen gehören nach wie vor zu den schwerwiegendsten Infektionskrankheiten mit insgesamt schlechter Prognose. Trotz medizinischem Fortschritt stellen diese Infektionen eine große diagnostische und therapeutische Herausforderung dar. Gefässprotheseninfektionen treten bei 1% bis 6% aller Gefässprothesenoperationen auf, wobei die Mortalitätsrate 20%-30% beträgt. Auch bei der infektiösen Endokarditis besteht trotz Verbesserung der medizinischen und chirurgischen Therapie immer noch eine schlechte Prognose. Insgesamt sind mehr Männer und Personen im Alter> 65 Jahre betroffen, wobei die geschätzten Inzidenzrate  3-9 Fälle/100’000 Personen pro Jahr beträgt. Typ und Virulenz der Pathogene, individuelle Patienten-charakteristika, Alter, Verzögerung der Diagnose und Zeitpunkt der Operation sind relevante Faktoren, die das Überleben des Patienten beeinflussen.

Das Projekt hat zum Ziel, Patienten mit kardiovaskulären Infektionen im Detail zu charakterisieren und dabei einen Link zur bakteriellen Pathophysiologie zu machen. Dabei wollen wir neben epidemiologischen Fragestellungen auch die Patientenperspektive,  biologische (Mikrobiom, Biomarker) Faktoren der Patienten und Umweltfaktoren untersuchen. Ausserdem wollen wir durch verbesserte moderne mikrobiologische Verfahren wie Whole genome sequencing, RNAseq, 16s rRNA Amplifikation die Diagnostik dieser Infektionen verbessern.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Das Projekt will dazu beitragen, durch personalisierte Medizin das Überleben von Patienten mit kardiovaskulären Infektionen zu verbessern. Ausserdem verspricht es durch die Kombination von Patientendaten, fortschrittlicher radiologischer Bildgebung, Analyse von Mikrobiom und Biomarkern ein differenziertes Verständnis dieser Infektionen zu generieren. Zugleich verspricht es detaillierte Aufschlusse uber das verursachende Pathogen durch translationale Forschung. Die beteiligten Forscher sind am Universitätsspital Zürich, am Institut für Medizinische Mikrobiologie und am Berliner Biofilm Center (Charité) angesiedelt. Kein einzelnes Mitglied der Beteiligten konnte das Projekt alleine durchführen, wobei der Wert in der engen interdisziplinären Zusammenarbeit besteht.


Direct link to Lay Summary Last update: 03.04.2019

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Polyester Vascular Graft Material and Risk for Intracavitary Thoracic Vascular Graft Infection.
Schweizer Tiziano A, Shambat Srikanth Mairpady, Haunreiter Vanina Dengler, Mestres Carlos A, Weber Alberto, Maisano Francesco, Zinkernagel Annelies S, Hasse Barbara (2020), Polyester Vascular Graft Material and Risk for Intracavitary Thoracic Vascular Graft Infection., in Emerging infectious diseases, 26(10), 2448-2452.
Diagnostic Accuracy of PET/CT and Contrast Enhanced CT in Patients With Suspected Infected Aortic Aneurysms
Husmann Lars, Huellner Martin W., Ledergerber Bruno, Eberhard Nadia, Kaelin Marisa B., Anagnostopoulos Alexia, Kudura Ken, Burger Irene A., Mestres Carlos-A., Rancic Zoran, Hasse Barbara, Anagnostopoulos A., Hasse (PI) B., Eberhard N., Hoffmann M., Husmann L., Kopp R., Ledergerber B., Rancic Z., Mestres C.A., Zbinden R., Zinkernagel A. (2020), Diagnostic Accuracy of PET/CT and Contrast Enhanced CT in Patients With Suspected Infected Aortic Aneurysms, in European Journal of Vascular and Endovascular Surgery, 59(6), 972-981.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ISCVID Lausanne (Switzerland) Talk given at a conference Mycobacterium chimaera Guidelines. 02.06.2020 Lausanne, Switzerland Hasse Barbara;
29th ECCMID Amsterdam (The Netherlands) Talk given at a conference The nightmare of Mycobacterium chimaera 13.04.2020 Amsterdam, Netherlands Hasse Barbara;
ISCVID Lausanne (Switzerland) Talk given at a conference Comparing the thoracic aortic graft infection risk based on two different types of vascular grafts: evidence from an in-vitro study. 02.04.2020 Lausanne, Switzerland Zinkernagel Annelies; Hasse Barbara; Ledergerber Bruno;
ISCVID Lausanne (Switzerland) Poster Usefulness of 18F-FDG-PET/CT in therapy control of Inflammatory and Mycotic Aneurysms. 02.04.2020 Lausanne, Switzerland Hasse Barbara; Husmann Lars; Ledergerber Bruno;
Infezioni disseminate da Mycobacterium chimaera in pazienti sottoposti ad intervento cardiochirurgico con by-pass cardiopolmonare Individual talk Overview on the current international guidelines for the diagnosis, treatment, and prevention of disseminated Mycobacterium chimaera infection following cardiac surgery with cardiopulmonary bypass. 28.01.2020 Venedig, Italy Hasse Barbara;
Veith Symposium New York Talk given at a conference NPWT for vascular graft infections: long-term results. 19.11.2019 New York, United States of America Rancic Zoran;
Veith Symposium New York Talk given at a conference In for a dime, in for a dollar, Use of PET/CT in vascular graft infections. 19.11.2019 New York, United States of America Rancic Zoran;
ESVS Annual Meeting Hamburg Talk given at a conference Usefulness of 18F-FDG-PET/CT in therapy control of Inflammatory and Mycotic Aneurysms. 24.09.2019 Hamburg, Germany Husmann Lars;
ESVS Annual Meeting, Hamburg Talk given at a conference Usefulness of 18F-FDG-PET/CT and contrast-enhanced CT for Diagnosis of Mycotic Aneurysms. 24.09.2019 Hamburg, Germany Husmann Lars;
Annual Meeting of the Swiss Society of Infectious Diseases, Lausanne, Switzerland Poster Early versus late onset vascular graft infections: microbiological spectrum and implications on antimicrobial therapy. 18.09.2019 Lausanne, Switzerland Ledergerber Bruno; Hasse Barbara; Rancic Zoran;
ISCVID Lausanne (Switzerland) Talk given at a conference Infection of root and ascending aortic grafts still a highly lethal condition: the Vasgra Cohort. 02.06.2019 Lausanne, Switzerland Ledergerber Bruno; Hasse Barbara;
ISCVID Lausanne (Switzerland) Poster Biofilm formation of Mycobacterium chimaera on polymers and on heart valves of infected patients: possible implications on treatment. 02.06.2019 Lausanne, Switzerland Hasse Barbara;
ECCMID Amsterdam (The Netherlands) Poster Open wounds and ongoing rifampin combination therapy are strongly associated with the development of rifampin resistance among staphylococcal vascular graft infections. 11.04.2019 Amsterdam, Netherlands Zinkernagel Annelies; Ledergerber Bruno; Hasse Barbara; Rancic Zoran;
ISCVID Lausanne (Switzerland) Poster Early versus late onset vascular graft infections: microbiological spectrum and implications on antimicrobial therapy. 02.04.2019 Lausanne, Switzerland Hasse Barbara; Ledergerber Bruno; Rancic Zoran;
ISCVID Lausanne (Switzerland) Poster Usefulness of 18F-FDG-PET/CT and contrast-enhanced CT for Diagnosis of Mycotic Aneurysms. 02.04.2019 Lausanne, Switzerland Ledergerber Bruno; Hasse Barbara; Husmann Lars; Rancic Zoran;


Associated projects

Number Title Start Funding scheme
204343 Tackling difficult-to-treat Staphylococcus aureus infections 01.12.2021 Project funding
176252 Staphylococcus aureus - persisting bacteria that are difficult to eradicate 01.10.2017 Project funding
163132 Cardiovascular prosthetic material infections 01.02.2016 Project funding (special)
144277 Vascular graft infections - epidemiology, best treatment options, imaging modalities and impact of negative pressure wound therapy 01.02.2013 Project funding

Abstract

Cardiovascular infections are an onging clinical problem despite the wide array of antibiotics currently available. Bacteria isolated from these infections may be in a biofilm-forming or non-growing state, thus tolerating antibiotic challenges. In-depth characterization of both the patient as well as the pathogenic bacteria will ultimately lead to personalized medicine. With this research project, we aim to establish a multidimensional assessment of patients with vascular graft infections (VGI), infective endocarditis (IE) and cardiovascular implantable electronic devices infections (CIEDI). This collaborative and interdisciplinary project at the University Hospital Zurich (USZ) relies on: (1) The existing, very close collaboration between infectious disease specialists, microbiologists, cardiovascular surgeons, cardiologists and imaging specialists (2) Two prospective, ongoing patient cohorts on patients with cardiovascular infections. (3) A dedicated team of cardiovascular surgeons with a strong interest in septic surgery. (4) A highly experienced nuclear medicine team familiar with the use and interpretation of 18F-FDG PET/CT (PET/CT). (5) The close collaboration with the Institute of Medical Microbiology (UZH) equipped with state-of-the-art microbiology techniques; and (6) an established research group in experimental bacteriology performing translational research on chronic and recurrent bacterial infections. With the first aim, we will carefully characterize patients with cardiovascular infections and establish a link to bacterial pathophysiology. We will continue our established SNF-funded cohort of patients with VGI (VASGRA) and the prospective IE/CIEDI cohort (ENVALVE). For in-depth pathophysiological investigations of these infections, we will continue our established biobank of blood, tissue and bacterial isolates. With the second aim, we will assess nested research questions. Based on the above-mentioned infrastructure, we will assess these patients based on their own perspectives, the host biology (including the microbiome, and inflammatory markers) and different environmental factors. Additionally, we will determine the impact of the interdisciplinary endocarditis board on patient's outcomes. Current treatment strategies (e.g. use of rifampin in staphylococcocal infections) and outcomes will be assessed and further optimized based on patient characteristics, biomarker kinetics, quality of life assesssments and imaging. We will also assess the role of parametric whole body dynamic PET/CT for VGI diagnosis.. Moreover, we will assess the clinical significance of incidental findings in PET/CT and probe the application of PET/CT for mycotic aneurysms and IE. We will also assess the need for device extraction/surgery among patients with early or late, hematogenous (symptoms <3 weeks) cardiovascular implantable electronic devices infections.With the third aim, we will probe the application of enhanced bacterial characterization ultimately resulting in enhanced bacterial diagnostics and treatment of biofilm-mediated cardiovascular infections. We will use different bacterial tools (e.g. Fluorescence in situ hybridization (FISH), 16s rRNA amplification, whole genome sequencing (WGS), RNAseq, 16s rRNA amplification) for enhanced diagnostics. The study on the microbiome of patients undergoing endovascular surgery with inguinal access will help understanding the pathogenesis of endovascular infections and thus improve prevention measures. We will assess whether the growth and structural characteristics of bacteria in biofilms can be linked to clinical outcome. This would provide an additional readout for determining treatment duration and the question which patients warrant prolonged anti-biofilm treatment or may profit from a shorter treatment and thus reduced stay in hospital.
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