# Feasibility of serial measurement of nitrite for pharmacodynamic monitoring and precision prescribing in urinary tract infections

## TL;DR

This study shows that measuring nitrite levels in urine can help track UTI progression and antibiotic effectiveness, potentially guiding personalized treatment.

## Contribution

The study demonstrates that serial nitrite measurements can differentiate between antibiotic-resistant and susceptible E. coli strains and correlate with bacterial load.

## Key findings

- Nitrite levels correlate with bacterial colony-forming unit counts in both in-vitro and clinical UTI samples.
- Amoxicillin-resistant E. coli strains continue to produce nitrite during treatment, while susceptible strains stop.
- Longitudinal nitrite monitoring can distinguish between resistant and susceptible E. coli in an in-vitro UTI model.

## Abstract

The ability to monitor host- and bacteria-specific biomarkers along with antimicrobial drug concentration at the site of infection offers potential for individualised approaches to antimicrobial therapy. Although urine collection is straightforward and directly linked to the infection site, the assessment of urinary tract infection (UTI) biomarkers during infection has not been extensively explored. The aim of this study is to evaluate the potential of monitoring urinary nitrite levels as a biomarker for antimicrobial pharmacodynamics in UTI treatment.

Resistant and susceptible E. coli strains were cultured in oxygen-free artificial urine, with amoxicillin added after 15 h. Colony-forming unit (CFU) counts, nitrite, and creatinine levels were measured at 5 timepoints over 66 h. Urine samples from 25 UTI patients and 25 non-UTI controls were analysed for bacterial growth, nitrite, and creatinine. Spearman rank correlation and Mann-Whitney U-tests were used for statistical analysis.

Our in-vitro model demonstrates that measuring the bacteria-specific urinary biomarker nitrite during E. coli growth in artificial urine can effectively be applied to assess antimicrobial pharmacodynamics over the course of UTI treatment. In an in-vitro UTI model, nitrite concentration can differentiate between resistant and susceptible E. coli strains and correlates with CFU counts. Analysis of 25 clinical UTI samples is consistent with these findings, showing correlations between nitrite levels and CFU counts.

Here we show that nitrite generation by E. coli may have clinical relevance as a biomarker for infection progression and antimicrobial treatment outcomes, offering a valuable tool for monitoring the pharmacodynamic responses to antimicrobial therapy in UTIs.

Urinary tract infections are common bacterial infections, and biomarkers like nitrite are often used to support their diagnosis. This study explores monitoring nitrite to assess urinary tract infection (UTI) progression and response to treatment. We show that amoxicillin-resistant bacteria continue producing nitrite during treatment, while susceptible bacteria stop producing the biomarker when their growth is effectively inhibited. We also show that as bacterial levels increase in artificial urine and patient urine, nitrite concentrations increase too. We show that measuring nitrite levels over time during a UTI could help doctors choose the best antibiotic and adjust treatment for each patient.

Stadler et al. evaluate the diagnostic value of urinary tract infection biomarker, nitrite, in predicting disease progression and treatment efficacy. The longitudinal measurement of nitrite in an in-vitro UTI distinguishes between amoxicillin-resistant and susceptible E. coli strains and correlates with bacterial colony-forming unit counts in-vitro and in clinical UTI.