NCCR AntiResist:: New Approaches to Combat Antibiotic-resistant Bacteria

University Hospital, Basel, Switzerland8,000 enrolled

Overview

This is an explorative, mono-center study including prospectively collected patient samples from the University Hospital of Basel. It is to investigate antimicrobial resistance (AMR) including three clinical manifestations of infectious diseases: urinary tract infection, pneumonia and deep-seated infections. The focus is on four bacteria (E. coli, Klebsiella species, S. aureus, P. aeruginosa) that are part of the high priority list of World Health Organization (WHO). Residual patient samples are analysed for proteomic, metabolomic and transcriptomic analysis, immunocytochemical or fluorescence in-situ hybridisation (FISH) analysis, flow cytometry analysis (FACS) and immunophenotyping and exploration of bacterial properties.

The National Center of Competence in Research (NCCR) AntiResist aims at utilizing patient samples in order to investigate the physiology of bacterial pathogens in human patients and establishing a unique multidisciplinary network of clinicians, biologists, engineers, chemists, computational scientists and drug developers. The goal of this project is to elucidate the physiological properties of bacterial pathogens in infected human patients in order to provide new ways of combatting superbugs. These clinical data will be used to guide and benchmark development of patient-mimicking and in-vitro models, accelerate the search for novel bacterial targets, antibacterial compounds and non-conventional strategies. In detail, the focus will be on three clinical manifestations of infectious diseases caused by four critical bacterial pathogens belonging to WHO "priority pathogens" list: E. coli, Klebsiella species, S. aureus and P. aeruginosa : A) Urinary tract infection B) Pneumonia C) Deep-seated infections D) Controls for A), B) and C) E) Clinical controls for A), B) and C) without obtained samples F) Analysis whether the application of Art. 34 HFV (Weiterverwendung biologischen Materials und/oder gesundheitsbezogener Personendaten für die Forschung bei fehlender Einwilligung und Information) can avoid a bias.

Study Type

OBSERVATIONAL

Enrollment

8,000

Conditions

Antimicrobial Resistance (AMR)

Interventions

analysis of antimicrobial resistanceOTHER

In samples from patients infected with one of the focus pathogens (E. coli, Klebsiella species, S. aureus, P. aeruginosa) will be: (i) isolated and pathogenic bacteria characterized; (ii) pathogen in-situ properties at single-cell and bulk average determined; (iii) human metabolites, proteins and cells determined (iv) antibiotic concentration determined (v) bacterial growth monitored Deducted from the data will be: 1. relevant human components and pathogen properties that are common to most patients with similar indication 2. underlying regulatory networks and triggers in pathogen cells and human tissues. Clinical outcomes (survival/mortality) and treatment response (response or failure) will be correlated to the in vitro retrieved host and bacterial data.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with confirmed (i) urinary tract infection, (ii) pneumonia (including patients after lung transplantation, cystic fibrosis) or (iii) deep-seated infection with focus pathogen: * E. coli * Klebsiella species * S. aureus * P. aeruginosa * Controls: no detectable bacteria in routine microbiology lab and no other infection site at inclusion of the sample and follow up for 10 days, signed general consent * Clinical controls without obtained samples, but with confirmed (i) urinary tract infection, (ii) pneumonia (including patients after lung transplantation, cystic fibrosis) or (iii) deep-seated infection with focus pathogen: * E. coli * Klebsiella species * S. aureus * P. aeruginosa Exclusion Criteria: * Patients who have refused research and reuse of their data/samples (e.g. general consent) or any other decline (e.g. Patientenverfügung). * other than one of the focus bacteria in routine microbiology lab * Age: \<18 years * Controls without signed general consent

Outcomes

Primary Outcomes

Clinical outcome: survival rate

Survival rate (correlated to the in vitro retrieved host and bacterial data. In vitro retrieved host and bacterial data include: Proteomics, Metabolomics, FISH, Histology, PCR/Microbial genome sequencing, Microbial transcriptome, Antibiotic concentration, Timelapse studies, phenotypic characterisations, molecular typing, innate immune response characterization, Antibiotic tolerance testing, Microfluidic systems, 3-D models, Transcriptomics, Flow cytometry (FACS))

Time frame: one time assessment at baseline

Clinical outcome: mortality rate

Mortality rate (correlated to the in vitro retrieved host and bacterial data. In vitro retrieved host and bacterial data include: Proteomics, Metabolomics, FISH, Histology, PCR/Microbial genome sequencing, Microbial transcriptome, Antibiotic concentration, Timelapse studies, phenotypic characterisations, molecular typing, innate immune response characterization, Antibiotic tolerance testing, Microfluidic systems, 3-D models, Transcriptomics, Flow cytometry (FACS))

Time frame: one time assessment at baseline

Treatment response (binary: yes/ no)

Treatment response (correlated to the in vitro retrieved host and bacterial data. In vitro retrieved host and bacterial data include: Proteomics, Metabolomics, FISH, Histology, PCR/Microbial genome sequencing, Microbial transcriptome, Antibiotic concentration, Timelapse studies, phenotypic characterisations, molecular typing, innate immune response characterization, Antibiotic tolerance testing, Microfluidic systems, 3-D models, Transcriptomics, Flow cytometry (FACS))

Time frame: one time assessment at baseline

NCCR AntiResist:: New Approaches to Combat Antibiotic-resistant Bacteria

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts