Direct Molecular Characterization of Bacteria From ICU and From the REHAB

Completed

• Conditions: Bacterial Infections

• Registration Number: NCT03475472
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

Investigators aim to directly investigate the molecular properties of bacteria from tracheal and urinary samples routinely taken in intensive care units (ICU) patients.

Detailed Description

Investigators goal is to determine major bacterial activities and properties in the infected patient as a basis for more targeted, efficient antimicrobial discovery. Investigators will determine the abundance of dozens to hundreds of pathogen proteins in the samples and in in vitro cultures of the same pathogen strains using cutting-edge ultra-sensitive proteomics approaches (Parallel reaction Monitoring (PRM), Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH-MS). Data will be analyzed using dedicated mass spectrometry and proteomics packages using parametric and non-parametric statistics (false discovery rate determination based on decoy databases; t-tests of log-transformed abundance data with Benjamin-Hochberg corrections for multiple testing, normal distribution of the data will be evaluated by Kolmogorov-Smirnov test).

Based on experience from in vitro and animal infection experiments, a sample size of 10 can reveal 2fold differences in protein abundance among 500 top proteins at a significance of α = 0.05 and a power of β = 0.8 (after correction for multiple testing). However, it is possible that human patient samples have higher variance compared to animal infection models. Investigators will thus use a sequential statistics approach in which they continuously adjust sample size estimates based on the variance of the accumulating data. It may be possible that no sufficient sample sizes for all bacterial pathogens of interest will be reached within two years.

Study Timeline

• Study Start: 2018-02-01
• Study First Submitted: 2018-02-14
• Study First Submitted QC: 2018-03-22
• Study First Posted: 2018-03-23
• Primary Completion: 2021-01-27
• Study Completion: 2021-01-27
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-16
• Last Update Posted: 2021-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 971

Inclusion Criteria

• confirmed infection of lung or urine by one or several members of a defined set of bacterial pathogens (Pseudomonas aeruginosa, E. coli, Klebsiella spp., Serratia marcescens, Enterobacter spp., Acinetobacter baumannii, Staphylococcus aureus, Streptococcus pneumonia

Exclusion Criteria

• Proof of a refusal to the general research consent
• No detected bacteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Abundance of pathogen proteins	once during study (February 2018 until June 2020) but no fixed timepoint	Determine the abundance of pathogen proteins in the samples and in in vitro cultures of the same pathogen strains using cutting-edge ultra-sensitive proteomics approaches (Parallel reaction monitoring, PRM, Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH-MS). Data will be analyzed using dedicated mass spectrometry and proteomics packages using parametric and non-parametric statistics (false discovery rate determination based on decoy databases; t-tests of log-transformed abundance data with Benjamin-Hochberg corrections for multiple testing, normal distribution of the data will be evaluated by Kolmogorov-Smirnov test).

Trial Locations

Locations (2)

REHAB Basel, Klinik für Neurorehabilitation und Paraplegiologie; 🇨🇭 Basel, Switzerland

Division of Infectious Diseas and Hospital Epidemiology; 🇨🇭 Basel, Switzerland