Feasibility of serial measurement of nitrite for pharmacodynamic monitoring and precision prescribing in urinary tract infections
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Date Issued
2025-07-01
Date Acceptance
2025-06-11
Citation
Communications Medicine, 2025, 5
ISSN
2730-664X
Publisher
Nature Portfolio
Journal / Book Title
Communications Medicine
Volume
5
Copyright Statement
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s43856-025-00969-6
Publication Status
Published
Article Number
ARTN 268