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

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.