Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Swiss National Science Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A) Urinary tract infection | Processing of residual urine for proteomic, metabolomic and transcriptomic analysis, immunocytochemical or fluorescence in-situ hybridisation (FISH) analysis, flow cytometry analysis (FACS), immunophenotyping. If positive for target bacteria: sample stored at biobank. If previous antibiotic treatment: plasma sample storage. Exploration of bacterial properties (Highly sensitive mass spectrometry, whole genome sequencing), expression of virulence factors, genomic alterations of bacterial species, metabolism, surface molecule expression, gene expression levels, cytokine levels, immune cell biology, antibiotic concentration (chromatography/mass spectrometry). Demographical, clinical, microbiological, laboratory, epidemiological and hospital-associated data will be analysed. 500 samples per target bacteria (S. aureus, P. aeruginosa, E. coli, Klebsiella species) included. First, a pilot study from randomly selected patients within each bacterial species group (n=50, each) is done. |
| |
| B) Pneumonia | Processing of residual samples (tracheal secretion, bronchioalveolar lavage (BAL)) for proteomic, metabolomic, transcriptomic and cytological analysis. If positive for target bacteria: sample stored at biobank. If previous antibiotic treatment: plasma sample storage. Exploration of bacterial properties. Demographical, clinical, microbiological, laboratory, epidemiological and hospital-associated data will be analysed. 500 samples per target bacteria (S. aureus, P. aeruginosa, E. coli, Klebsiella species) included. |
| |
| C) Deep-seated infections | Processing of intraoperative material residual samples for proteomic, metabolomic, transcriptomic and cytological analysis. If positive for target bacteria: sample stored at biobank. Exploration of bacterial properties. Demographical, clinical, microbiological, laboratory, epidemiological and hospital-associated data will be analysed. 500 samples per target bacteria (S. aureus, P. aeruginosa, E. coli, Klebsiella species) included. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| analysis of antimicrobial resistance | Other | 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:
Clinical outcomes (survival/mortality) and treatment response (response or failure) will be correlated to the in vitro retrieved host and bacterial data. |
| Measure | Description | Time Frame |
|---|---|---|
| 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)) | 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)) | 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)) | one time assessment at baseline |
Not provided
Not provided
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:
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:
Exclusion Criteria:
Not provided
Not provided
Not provided
Patient samples during routine collection at the University Hospital of Basel from November 2020 to approximately December 2024.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nina Khanna, Prof. | Contact | +41 61 328 73 25 | nina.khanna@usb.ch | |
| Christoph Dehio, Prof. | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Nina Khanna, Prof. | University Hospital Basel, Division of Infectiology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Recruiting | Basel | 4031 | Switzerland |
Not provided
| ID | Term |
|---|---|
| D014552 | Urinary Tract Infections |
| D011014 | Pneumonia |
| D004927 | Escherichia coli Infections |
| D007710 | Klebsiella Infections |
| D013203 | Staphylococcal Infections |
| D000098968 | Community-Acquired Pneumonia |
| D000077299 | Healthcare-Associated Pneumonia |
| D053717 | Pneumonia, Ventilator-Associated |
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
Not provided
Not provided
Not provided
Not provided
Not provided
Residual samples from routinely collected material (urine, tracheal secretion in intubated patients, sputum in cystic fibrosis patients, bronchoalveolar lavage fluid, blood, deep-seated infectious material that is surgically removed).
|
| D) Controls for A), B) and C) | Control samples result from patients with a suspected infection (infection sites A), B) or C), in which no microbiological confirmed infection has been diagnosed. Storage at biobank |
|
| E) Clinical controls for A), B) and C) without obtained samples | For clinical controls, clinical characteristics of patients with detection of target pathogens in their routine samples (but which could not be included for sample analysis in this study) will be assessed. |
|
| F) Cohort with analysis whether the application of Article (Art) 34 HFV can avoid a bias | Since part of the data and samples in this study are collected with the representative consent of the ethics committees, it is investigated whether the application of Art. 34 HFV prevents selection bias with respect to the study population. For this purpose, differences between the actual study population using Art. 34 HFV and the study population with provided research consent will be descriptively investigated in terms of the prevalence of multi-resistant germs and other available population characteristics. |
|
|
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D016908 | Gram-Positive Bacterial Infections |
| D017714 | Community-Acquired Infections |
| D003428 | Cross Infection |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |