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

NCCR AntiResist: Mono-center Study to Identify New Approaches to Combat Antibiotic-resistant Bacteria.

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.

Study Overview

• Status: Recruiting
• Conditions: Antimicrobial Resistance (AMR)
• Intervention / Treatment: Other: analysis of antimicrobial resistance

Detailed Description

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 (Estimated): 8000

Contacts and Locations

• Study Contact: Name: Nina Khanna, Prof.; Phone Number: +41 61 328 73 25; Email: nina.khanna@usb.ch
• Study Contact Backup: Name: Christoph Dehio, Prof.

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Nina Khanna, Prof. Dr. med.; Phone Number: +41 61 328 73 25; Email: nina.khanna@usb.ch
    • Contact: Richard Kühl, Dr. med.; Phone Number: +41 61 328 65 45; Email: richard.kuehl@usb.ch
    • Principal Investigator: Nina Khanna, Prof.
    • Sub-Investigator: Richard Kühl, Dr.
    • Sub-Investigator: Adrian Egli, Prof.
    • Sub-Investigator: Christoph Dehio, Prof.
    • Sub-Investigator: Mario Morgenstern, PD
    • Sub-Investigator: Martin Siegemund, Prof.
    • Sub-Investigator: Daiana Stolz, Prof.
    • Sub-Investigator: Sarah Tschudin Sutter, Prof.
    • Sub-Investigator: Bram Stieltjes, Dr.
    • Sub-Investigator: Dirk Buman, Prof.
    • Sub-Investigator: Urs Jenal, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.
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; 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: relevant human components and pathogen properties that are common to most patients with similar indication; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Nina Khanna, Prof., University Hospital Basel, Division of Infectiology

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pneumonia; S. aureus; E. coli; P. aeruginosa; Ventilator-associated pneumonia (VAP); Hospital-acquired pneumonia (HAP); Urinary tract infection (UTI); Klebsiella species; National Center of Competence in Research (NCCR); Deep-seated infections; bacterial properties; Community-acquired pneumonia (CAP); cystic fibrosis (CF)
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: 2020-02588; pe20Khanna

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No