Clinical trial NCT05674032: Bacterial Metallophores in the Diagnosis of Acute Pyelonephritis
Official title: Detection of Causative Agents of Acute Pyelonephritis Using Bacterial Metallophores
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Pyelonephritis
Complicated Urinary Tract Infection
Keywords: metallophores
mass spectrometry
acute pyelonephritis
complicated urinary tract infection
siderophores
yersiniabactin
Lead sponsor: Thomayer University Hospital
Sponsor class: OTHER
Collaborators: name: Czech Academy of Sciences
First posted: 2023-01-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting to the department of urology and fulfilling eligibility criteria.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Detection of metallophores
timeFrame: through study completion, an average of 1 year
measure: Classification of microorganisms
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Metallophores versus culture
timeFrame: through study completion, an average of 1 year
measure: Cases versus Controls 1 versus Controls 2
timeFrame: 1 year after study completion
Other outcomes:
Locations:
city: Praha
country: Czechia
facility: Thomayer University Hospital
Study officials:
affiliation: Thomayer University Hospital
name: Jan Hrbacek, PhD.
role: STUDY_DIRECTOR
References:
citation: Bonkat G, Bartoletti R, Bruyère F, Cai T, Geerlings SE, Köves B, et al. Guidelines on Urological Infections. 2020. Vallejo-Torres L, Pujol M, Shaw E, Wiegand I, Vigo JM, Stoddart M, et al. Cost of hospitalised patients due to complicated urinary tract infections: A retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: The COMBACTE-MAGNET, RESCUING study. BMJ Open 2018;8:1-9. https://doi.org/10.1136/bmjopen-2017-020251. Hrbacek J, Cermak P, Zachoval R. Current antibiotic resistance trends of uropathogens in central europe: Survey from a tertiary hospital urology department 2011-2019. Antibiotics 2020;9:1-11. https://doi.org/10.3390/antibiotics9090630. Hyun M, Noh CI, Ryu SY, Kim HA. Changing trends in clinical characteristics and antibiotic susceptibility of Klebsiella pneumoniae bacteremia. Korean J Intern Med 2018;33:595-603. Caza M, Kronstad J. Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans. Front Cell Infect Microbiol 2013;4:1-23. https://doi.org/10.3389/fcimb.2013.00080. Prichystal J, Schug K, Lemr K, Novak J, Havlicek V. Structural analysis of natural products. Anal Chem 2016;88:10338-46. Václavková J, Ozdian T, Hajdúch M, Džubák P. Body fluids as a source of prote-omic biomarkers of various diseases. Chem List 2020;114:209-15 Skriba A, Pluhacek T, Palyzova A, Novy Z, Lemr K, Hajduch M, et al. Early and non-invasive diagnosis of aspergillosis revealed by infection kinetics monitored in a rat model. Front Microbiol 2018;9:1-7. https://doi.org/10.3389/fmicb.2018.02356. Hrbacek J, Morais D, Cermak P, Hanacek V, Zachoval R. Alpha-diversity and microbial community structure of the male urinary microbiota depend on urine sampling method. Sci Rep 2021;11. https://doi.org/10.1038/s41598-021-03292-x.