Comparison Shows that Multiplex Polymerase Chain Reaction Identifies Infection-associated Urinary Biomarker–positive Urinary Tract Infections That Are Missed by Standard Urine Culture

Haley, Emery; Luke, Natalie; Mathur, Mohit; Festa, Richard A.; Wang, Jimin; Jiang, Yan; Anderson, Lori; Baunoch, David

doi:10.1016/j.euros.2023.10.008

Cited by 10 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high sensitivity and specificity (> 90%) of the “Consensus” biomarker model for UTIs makes it a valuable tool to differentiate true UTI cases from asymptomatic bacteriuria and other false-positive differential diagnoses, and also for establishing an objective “truth” for the comparison of existing and novel diagnostic test accuracy. This is especially important since the current “gold standard” test, SUC, is known to have significant limitations, making it an unreliable source of diagnostic “truth.” Specifically, this study (Supplemental Table S20 ) and others have illustrated the low sensitivity of SUC for non- E. coli organisms and polymicrobial infections [ 16 , 34 – 37 ].…”

Section: Discussionmentioning

confidence: 78%

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

Akhlaghpour,

Haley,

Parnell

et al. 2024

BMC Infect Dis

Self Cite

View full text Add to dashboard Cite

Background Current diagnoses of urinary tract infection (UTI) by standard urine culture (SUC) has significant limitations in sensitivity, especially for fastidious organisms, and the ability to identify organisms in polymicrobial infections. The significant rate of both SUC “negative” or “mixed flora/contamination” results in UTI cases and the high prevalence of asymptomatic bacteriuria indicate the need for an accurate diagnostic test to help identify true UTI cases. This study aimed to determine if infection-associated urinary biomarkers can differentiate definitive UTI cases from non-UTI controls. Methods Midstream clean-catch voided urine samples were collected from asymptomatic volunteers and symptomatic subjects ≥ 60 years old diagnosed with a UTI in a urology specialty setting. Microbial identification and density were assessed using a multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and SUC. Three biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), and Interleukins 8 and 1β (IL-8, and IL-1β)] were also measured via enzyme-linked immunosorbent assay (ELISA). Definitive UTI cases were defined as symptomatic subjects with a UTI diagnosis and positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were defined as asymptomatic volunteers. Results We observed a strong positive correlation (R2 > 0.90; p < 0.0001) between microbial density and the biomarkers NGAL, IL-8, and IL-1β for symptomatic subjects. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 84.0%, specificity 91.2%, positive predictive value 93.7%, negative predictive value 78.8%, accuracy 86.9%, positive likelihood ratio of 9.58, and negative likelihood ratio of 0.17 in differentiating definitive UTI from non-UTI cases, regardless of non-zero microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases. Conclusion We demonstrated that positive infection-associated urinary biomarkers NGAL, IL-8, and IL-1β, in symptomatic subjects with positive SUC and/or M-PCR results was associated with definitive UTI cases. A consensus criterion with ≥ 2 of the biomarkers meeting the positivity thresholds showed a good balance of sensitivity (84.0%), specificity (91.2%), and accuracy (86.9%). Therefore, this biomarker consensus is an excellent supportive diagnostic tool for resolving the presence of active UTI, particularly if SUC and M-PCR results disagree.

show abstract

Section: Discussionmentioning

confidence: 78%

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

Akhlaghpour,

Haley,

Parnell

et al. 2024

BMC Infect Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Six studies were classified as having high risk of bias ( 36 , 38 – 40 , 43 , 49 ). Seven remaining studies had unclear risk of bias ( 37 , 45 , 51 , 52 , 54 – 56 ). Details on the rating of each risk of bias are shown in Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Sixteen studies were rated as having low risk of all three domain of applicability concerns ( 5 , 37 , 41 , 42 , 44 – 48 , 50 – 53 , 57 – 59 ). Seven studies were classified as having high risk of applicability concerns ( 36 , 38 – 40 , 43 , 49 , 54 ). Two studies had unclear risk of applicability concern ( 55 , 56 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis

Zhang,

Chen,

Mitsnefes

et al. 2024

Front. Pediatr.

View full text Add to dashboard Cite

IntroductionEarly and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms.MethodsOur systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients.ResultsWe found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results.DiscussionThe level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).

show abstract

Clinical utility of PCR compared to conventional culture and sensitivity testing for management of complicated urinary tract infections in adults: Part II.Evaluation of diagnostic concordance, discordant results, and antimicrobial selection efficacy

Spangler,

Williams,

Aberger

et al. 2025

Diagnostic Microbiology and Infectious Disease

View full text Add to dashboard Cite

Comparison Shows that Multiplex Polymerase Chain Reaction Identifies Infection-associated Urinary Biomarker–positive Urinary Tract Infections That Are Missed by Standard Urine Culture

Cited by 10 publications

References 29 publications

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis

Clinical utility of PCR compared to conventional culture and sensitivity testing for management of complicated urinary tract infections in adults: Part II.Evaluation of diagnostic concordance, discordant results, and antimicrobial selection efficacy

Contact Info

Product

Resources

About