Urinary tract infections (UTIs) are among the most common infections and represent a major antibiotic exposure burden worldwide. Currently, UTI diagnosis is based on clinical symptoms, laboratory results, and/or imaging findings. Although the gold standard for diagnosing UTI is urine culture, it is time consuming and labor-intensive, leading to delays or inappropriate antibiotic prescriptions. Therefore, there is a need for novel and rapid UTI diagnostics to enable better treatment.
Novel diagnostics for UTIs should mainly focus on the host response or the pathogen. Pathogen-focused methods can be conventional such as urine culture and urine microscopy which are slow and labor-intensive. Alternatively, methods such as Multiplex PCR, MALDI-TOF mass spectroscopy, sequence-based diagnostics are rapid but require well-trained experts and costly instrumentation. Host-focused diagnostics that identify biomarkers or biomarker panels are particularly attractive since they can better distinguish infection from "colonization" [1]. Cytokines and urinary neutrophil gelatinase-associated lipocalin (U-NGAL) are two sets of host-response biomarkers currently being explored [2]. As cytokines are key components of the host response, these are promising biomarkers for differentiating upper and lower UTIs—especially IL-6 and IL-8. However, elevated concentrations are non-specific since they are high in various inflammatory response diseases. Thus, the use of cytokines to diagnose UTIs is limited [2]. In contrast, U-NGAL has been reported to have high sensitivity and specificity in diagnosing UTIs. While U-NGAL was identified first as biomarker for acute kidney injury, it has recently been shown to be significantly elevated in gram-negative UTIs in both adults and children, and also shows utility for prognosis, as concentrations correlate with the duration of infection. The limitation of U-NGAL to diagnose UTIs is that it is a common maker of kidney injury, so it may be elevated in other conditions as well [2].
In addition to biomarker development, another consideration is multivariate analysis to incorporate multiple biomarker results into a single screen result to predict or rule out the possibility of UTI. A novel prediction algorithm, termed the Urinalysis-based Timely and On-the-spot Prediction of Infection Algorithm (UTOPIA), was initially proposed by Kim, et al [3]. The UTOPIA equation was designed to predict positive urine culture results with the multivariable including demographic conditions (age of higher risk and sex) and results of urinalysis (nitrite, leukocyte esterase, the numbers of white blood cells and bacteria) [3]. At our institution, we have validated the diagnostic performance of the UTOPIA value in a pediatric group. Urinalysis results from January 2019 to December 2020 were analyzed with the UTOPIA algorithm and receiver operating characteristics curves were constructed. The area under the curve of the UTOPIA value was 0.825, which is significantly higher than the individual components.
In summary, the novel UTOPIA approach is a promising solution for more rapid UTI diagnosis. However, a combination of multivariable prediction panel with suitable biomarkers like U-NGAL may yield even better results. Further studies will need to validate these novel methods to determine their benefits and cost effectiveness.
REFERENCES
- Patel, R., et al., Envisioning Future Urinary Tract Infection Diagnostics. Clin Infect Dis, 2022. 74(7): p. 1284-1292.
- Horvath, J., et al., Biomarkers in urinary tract infections - which ones are suitable for diagnostics and follow-up? GMS Infect Dis, 2020. 8: p. Doc24.
- Kim, D., et al., Prediction of urine culture results by automated urinalysis with digital flow morphology analysis. Sci Rep, 2021. 11(1): p. 6033.