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

NCT05017766 | Recruiting

• 1 other identifier: 2020-02588; pe20Khanna
• Study Type: observational
• Target: 8,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antimicrobial Resistance (AMR)

Keywords

National Center of Competence in Research (NCCR); Urinary tract infection (UTI); Pneumonia; Deep-seated infections; E. coli; Klebsiella species; S. aureus; P. aeruginosa; bacterial properties; Community-acquired pneumonia (CAP); Hospital-acquired pneumonia (HAP); Ventilator-associated pneumonia (VAP); cystic fibrosis (CF)

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (6)

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.

Other: analysis of antimicrobial resistance

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.

Other: analysis of antimicrobial resistance

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.

Other: analysis of antimicrobial resistance

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

Other: analysis of antimicrobial resistance

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.

Other: analysis of antimicrobial resistance

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.

Other: analysis of antimicrobial resistance

Interventions

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: 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.

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) Cohort with analysis whether the application of Article (Art) 34 HFV can avoid a bias

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient samples during routine collection at the University Hospital of Basel from November 2020 to approximately December 2024.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

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).

MeSH Terms

Conditions

Urinary Tract Infections; Pneumonia; Escherichia coli Infections; Klebsiella Infections; Staphylococcal Infections; Community-Acquired Pneumonia; Healthcare-Associated Pneumonia; Pneumonia, Ventilator-Associated; Cystic Fibrosis

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Community-Acquired Infections; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pancreatic Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Nina Khanna, Prof.

  University Hospital Basel, Division of Infectiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nina Khanna, Prof.

CONTACT

+41 61 328 73 25; nina.khanna@usb.ch

Christoph Dehio, Prof.

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 24, 2021
• Study Start: December 3, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

CH (1)