418 - Dual-transcriptomics for characterization of UTI in children with neurogenic bladder who perform clean intermittent catheterization

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 418
Publication Number: 418.418

Elaise Hill, Children's National Health System, BETHESDA, MD, United States; Briony K. Varda, Children's National Health System, Washington, DC, United States; Marcos Perez-Losada, The George Washington University, Washington, DC, United States; Michael Hsieh, Children's National Hospital, Washington, DC, United States

Presenting Author(s)

EH

Elaise Hill, MD (she/they)

attending physician
Children's National Health System
BETHESDA, Maryland, United States

Background: Children with neurogenic bladder who perform clean intermittent catheterization (CIC) are at an increased risk of urinary tract infection (UTI). The distinction between asymptomatic bacteriuria and UTI in children with CIC-dependence is important as failure to treat can lead to morbidity and mortality, while over-treatment with antibiotics leads to drug resistance. Little is known about the interaction between host and bacteria in children with CIC-dependence changes during infection.

Objective: To apply dual-transcriptomics utilizing dual RNA-Seq to identify how microbes functionally change host response and identify novel signatures of UTI in children who perform CIC.

Design/Methods:

This is a proof-of-concept study from a single center pediatric emergency department. Eight children were enrolled. Inclusion criteria: ≤ 21 years with neurogenic bladder and CIC-dependence, with a urinalysis and culture collected for clinical evaluation. UTI was defined as the presence of pyuria, ≥ 10 white blood cells per high-power field on microscopy or positive leukocyte esterase on dipstick urinalysis, plus a positive urine culture, ≥100,000 colony forming units per milliliter of a potential urinary pathogen, and ≥ two signs or symptoms of UTI.

RNA was extracted and sequenced using RNA-Seq through the NovaSeq 6000 system. Host and pathogen sequences were separated and aligned to the RefSeq database. Microbial and human reads were utilized to explore expression patterns. Patient demographic data was analyzed by t-test for continuous data and through Chi-square testing for proportional or categorical data.

Results: Three patients met initial clinical criteria and two patients met the strict final definition of UTI including positive urine culture. Most clinical samples contained evidence of more than one bacterium on RNA analysis, however, identified bacteria were typical of UTI, including mostly gram-negative species. RNA was successfully purified and transcriptomics was performed on 5 of 8 urine samples, three of which had low RNA concentration. 24 novel RNA transcripts with at least a threefold difference in expression between groups were identified.

Conclusion(s):

Dual-transcriptomics was successfully performed for the first time on children with neurogenic bladder who perform CIC. Novel RNA biomarkers were identified which may further characterize UTI in patients who perform CIC, however a larger study is needed to identify a clear biosignature of infection.