Acute Pyelonephritis, Complicated Urinary Tract Infection
Conditions
Keywords
metallophores, mass spectrometry, acute pyelonephritis, complicated urinary tract infection, siderophores, yersiniabactin
Brief summary
The project aims to investigate bacterial metallophores as potential diagnostic markers of acute pyelonephritis and complicated urinary tract infections. These secondary metabolites are excreted by pathogenic microorganims in the course of infection for the uptake of iron and other metallic ions from the host. They are species-specific and can be detected in body fluids (including urine) by mass spectrometry. The potential contribution of this project is a culture-independent method for the diagnosis of the causative microbiological agent.
Detailed description
Acute pyelonephritis (AP) is a clinical syndrome characterized by fever, chills, nausea vomiting and costovertebral angle tenderness, bacteriuria and pyuria. The underlying pathophysiology is based on the presence of microbes in the renal parenchyma which may progress to sepsis. Complicated urinary tract infection (cUTI) is one accompanied by abnormalities of the urinary tract or host factors which make the eradication of the infection difficult. The most common etiological agents include gram-negative enteric rods, i.e. E. coli, Klebsiella pneumoniae; and Enterococcus spp. Empirical antibiotic treatment should be targeted once culture and sensitivity results become available. This usually takes 24-48 hours, occasionally even 72 hours. Inadequate antibiotic treatment leads to higher mortality if the etiological agent is of a multi-drug resistant phenotype. Metallophores are a major virulence factor of bacterial pathogens. These are chelating molecules secreted by the microbe for the uptake of iron, copper, and other metals from the host. E.g., siderophores aim at Fe3+ ions removal from the host protein molecules; the complex then adheres to specific extracellular receptors on the microbial cell and is internalized. Yersiniabactin is another metallophore which binds copper. Proteomic analysis using mass spectrometry has been used in the detection of biomarkers for several pathological conditions: renal failure, post-transplant nephropathy, various malignancies etc. Metallophores can be detected by mass spectrometry.
Interventions
None listed
Sponsors
Czech Academy of Sciences
Thomayer University Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* in-patient with clinical signs and symptoms of AP/cUTI or out-patient with clinical signs and symptoms of acute uncomplicated pyelonephritis or in-patient with no clinical signs of UTI and a negative standard urine culture result
Exclusion criteria
* inability to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Detection of metallophores | through study completion, an average of 1 year | The detection of metallophores in urine samples |
| Classification of microorganisms | through study completion, an average of 1 year | Taxonomic classification of the pathogenic microorganism using its metallophores |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metallophores versus culture | through study completion, an average of 1 year | The comparison of standard urinary culture results with those obtained from mass spectrometry analysis |
| Cases versus Controls 1 versus Controls 2 | 1 year after study completion | The comparison of the detection of metalophores in cases with AP/cUTI versus acute uncomplicated cystitis versus urinary tract infection-free individuals |
Countries
Czechia
Contacts
Primary ContactJan Hrbacek, PhD.
Backup ContactRoman Zachoval, Prof.
Outcome results
None listed