Urinary Tract Infections in Cirrhosis

Evaluate the prevalence and types of urinary tract infections, the features of the gut and urinary tract microbiota in cirrhosis, to assess its importance in the development of complications and outcomes of cirrhosis.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Urinary Tract Infections
• Intervention / Treatment: Diagnostic test: 16S rRNA gene sequencing

Detailed Description

Asymptomatic bacteriuria in an individual without urinary tract symptoms is defined by a mid-stream sample of urine showing bacterial growth > 105 cfu/mL in two consecutive samples in women and in one single sample in men. A complicated urinary tract infections occurs in an individual in whom factors related to the host (e.g. underlying diabetes or immunosuppression) or specific anatomical or functional abnormalities related to the urinary tract. Laboratory urine culture is the recommended method to determine the presence or absence of clinically significant bacteriuria.

Catheter-associated urinary tract infections refers to urinary tract infections occurring in a person whose urinary tract is currently catheterised or has been catheterised within the past 48 hours. Signs and systemic symptoms compatible with сatheter-associated urinary tract infections include new onset or worsening of fever, rigors, altered mental status, malaise, or lethargy with no other identified cause, flank pain, costovertebral angle tenderness, acute haematuria, pelvic discomfort and in those whose catheters have been removed dysuria, urgent or frequent urination and suprapubic pain or tenderness. Microbiologically, сatheter-associated urinary tract infections is defined by microbial growth of > 103 cfu/mL of one or more bacterial species in a single catheter urine specimen or in a mid-stream voided urine specimen from a patient whose urethral, suprapubic, or condom catheter has been removed within the previous 48 hours.

• Study Type: Observational
• Enrollment (Anticipated): 35

Contacts and Locations

• Study Contact: Name: Ekaterina Malaeva, PhD; Phone Number: +375 29 338 07 08; Email: dr-malaeva@mail.ru

Study Locations

• Belarus
  • Ilicha Str. 286
    • Gomel, Ilicha Str. 286, Belarus, 246013
      • Recruiting
      • Gomel State Clinical Hospital №3
      • Contact: Marina Menshakova, MD; Phone Number: +375 232 53 37 83; Email: ggkb3@mail.gomel.by

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Prospective observational longitudinal multicenter study

Description

Inclusion Criteria:

• clinical diagnosis of cirrhosis

Exclusion Criteria:

• human immunodeficiency virus or acquired immune deficiency syndrome
• autoimmune diseases
• oncology
• organ transplantation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with cirrhosis and urinary tract infections; Participants collect urine and fecal specimens at first two days when they admit to hospital, after 7-10 days and last two days hospital treatment and during episodes of complications (variceal bleeding, hepatic coma, hepatorenal syndrome). Urine samples take from patients via clean catch if the patient not have a catheter placed, otherwise take from urinary catheters if present. Straight catheterization utilize if the patient unable to void and doesn't have a catheter placed. Fecal specimens collect using a toilet specimen collection kit. Clinical, standart laboratory and cultural test, molecular genetic methods, using 16S rRNA gene sequencing of the V4-V5 hypervariable region be administered.	Diagnostic test: 16S rRNA gene sequencing; DNA extraction and 16S rRNA gene sequencing DNA extraction, 16S rRNA gene amplification, and deep sequencing of the 16S rRNA amplicon performe. The V4-V5 region of the 16S rRNA gene amplify with barcodes for multiplexing.
Participants with cirrhosis without urinary tract infections; Participants ask to collect urine and fecal specimens at first two days when they admit to hospital, after 7-10 days and last two days hospital treatment and during episodes of complications (variceal bleeding, hepatic coma, hepatorenal syndrome). Urine samples take from patients via clean catch if the patient not have a catheter placed, otherwise take from urinary catheters if present. Straight catheterization utilize if the patient unable to void and doesn't have a catheter placed. Fecal specimens collect using a toilet specimen collection kit. Clinical, standart laboratory and cultural test, molecular genetic methods, using 16S rRNA gene sequencing of the V4-V5 hypervariable region be administered.	Diagnostic test: 16S rRNA gene sequencing; DNA extraction and 16S rRNA gene sequencing DNA extraction, 16S rRNA gene amplification, and deep sequencing of the 16S rRNA amplicon performe. The V4-V5 region of the 16S rRNA gene amplify with barcodes for multiplexing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with variceal bleeding	The main diagnostic method of variceal bleeding is endoscopy	from the date of assignment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 3 months
Number of Participants with hepatic coma	hepatic encephalopathy is graded with the West Haven Criteria: Grade 0 - No obvious changes other than a potentially mild decrease in intellectual ability and coordination Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation Grade 4 - Coma	from the date of assignment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 3 months
Number of Participants with hepatorenal syndrome	Type-1 hepatorenal syndrome is characterized by a rapid deterioration of renal function with a doubling of serum creatinine to values above 2.5 mg/dl within 2 weeks, type-2 hepatorenal syndrome is characterized by a slower increase in serum creatinine to values above 1.5 mg/dl. The main clinical characteristic of Type-1 hepatorenal syndrome is acute renal failure, while the main characteristic of type-2 hepatorenal syndrome is refractory ascites.	from the date of assignment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 3 months

Collaborators and Investigators

• Sponsor: Gomel State Medical University
• Investigators: Principal Investigator: Igor Stoma, D.Sc., Gomel State Medical University

Publications and helpful links

General Publications

• Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010 Oct;139(4):1246-56, 1256.e1-5. doi: 10.1053/j.gastro.2010.06.019. Epub 2010 Jun 14.
• Mestrovic T, Matijasic M, Peric M, Cipcic Paljetak H, Baresic A, Verbanac D. The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics (Basel). 2020 Dec 22;11(1):7. doi: 10.3390/diagnostics11010007.
• Neugent ML, Hulyalkar NV, Nguyen VH, Zimmern PE, De Nisco NJ. Advances in Understanding the Human Urinary Microbiome and Its Potential Role in Urinary Tract Infection. mBio. 2020 Apr 28;11(2):e00218-20. doi: 10.1128/mBio.00218-20.

Helpful Links

• In patients with cirrhosis, infections increase mortality 4-fold; 30% of patients die within 1 month after infection and another 30% die by 1 year.
• Consequently, studying the relationship between gut microbiota and the subsequent development of bacteriuria and UTI represents an important field of research.
• The contribution of the urinary tract microbiome to urinary tract infection and recurrent urinary tract infection

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2022
• Primary Completion (Actual): April 10, 2022
• Study Completion (Anticipated): April 5, 2024

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Urologic Diseases; Disease Attributes; Liver Diseases; Fibrosis; Infections; Communicable Diseases; Liver Cirrhosis; Urinary Tract Infections
• Other Study ID Numbers: 2.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: individual participant data (IPD) will no available to other researchers.

Drug and device information, study documents

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