Bacterial Metallophores in the Diagnosis of Acute Pyelonephritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Detection of Causative Agents of Acute Pyelonephritis Using Bacterial Metallophores

Conditions
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Acute Pyelonephritis, Complicated Urinary Tract Infection

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>In-patients with AP or cUTI admitted for treatment to the hospital. | |
| Control group 1<br>Out-patients seeking treatment for uncomplicated acute cystitis. | |
| Control group 2<br>In-patients admitted to the ward without signs and symptoms of a urinary tract infection and with a negative urine culture result. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of metallophores | The detection of metallophores in urine samples | through study completion, an average of 1 year | 
| Classification of microorganisms | Taxonomic classification of the pathogenic microorganism using its metallophores | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metallophores versus culture | The comparison of standard urinary culture results with those obtained from mass spectrometry analysis | through study completion, an average of 1 year | 
| Cases versus Controls 1 versus Controls 2 | The comparison of the detection of metalophores in cases with AP/cUTI versus acute uncomplicated cystitis versus urinary tract infection-free individuals | 1 year after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metallophores, mass spectrometry, acute pyelonephritis, complicated urinary tract infection, siderophores, yersiniabactin