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1.
Pediatr Nephrol ; 39(2): 483-491, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37462743

RESUMEN

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Pielonefritis , Infecciones Urinarias , Niño , Humanos , Interleucina-8/orina , Receptor Toll-Like 4 , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Pielonefritis/diagnóstico , Biomarcadores
2.
J Infect Chemother ; 30(8): 768-772, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38387786

RESUMEN

INTRODUCTION: Qualitative urinalysis using the Sternheimer stain is a common method in Japan for identifying bacteriuria, but there is a lack of studies examining its test characteristics. In this study, we aimed to investigate the sensitivity and specificity of the Sternheimer stain for urine culture results and compare it with the sensitivity and specificity of the Gram stain. Our goal was to determine the usefulness of the Sternheimer stain in identifying bacteriuria. PATIENTS AND METHODS: Among 986 patients aged 16 years or older from whom samples for both urinalysis and urine culture were obtained at the emergency room of Tenri Hospital from January 2019 to December 2019, 342 patients with pyuria, defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, who had not received prior antimicrobial therapy were included. Urine cultures were used for comparison to determine the sensitivity and specificity of Sternheimer and Gram stain in this patient group. A positive Sternheimer stain result was defined as bacteriuria ≥ (1+), and that of Gram stain was defined as ≥ 1/1 field of high-power ( × 1000) oil immersion. RESULTS: Using urine culture results for comparison, the sensitivity of Sternheimer stain was 92.2%, the specificity was 48.5%, the positive likelihood ratio was 1.79, and the negative likelihood ratio was 0.16. DISCUSSION: Sternheimer stain is a rapid and useful method to exclude bacteriuria in a group of patients with pyuria in the emergency department.


Asunto(s)
Bacteriuria , Servicio de Urgencia en Hospital , Violeta de Genciana , Fenazinas , Sensibilidad y Especificidad , Urinálisis , Infecciones Urinarias , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina , Urinálisis/métodos , Adulto , Anciano , Bacteriuria/diagnóstico , Bacteriuria/microbiología , Bacteriuria/orina , Japón , Coloración y Etiquetado/métodos , Adulto Joven , Piuria/diagnóstico , Piuria/orina , Adolescente , Anciano de 80 o más Años
3.
BMC Pediatr ; 24(1): 294, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38698354

RESUMEN

BACKGROUND: Urinary tract infections (UTIs) are a common cause of acute illness among infants and young children. There are numerous methods for collecting urine in children who are not toilet trained. This review examined practice variation in the urine collection methods for diagnosing UTI in non-toilet-trained children. METHODS: A systematic review was completed by searching MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), and JBI (Ovid) from January 1, 2000 until October 9, 2021 and updated on May 24, 2023. Studies were included if they were conducted in an acute care facility, examined pre-toilet trained children, and compared one urine collection method with another for relevant health care outcomes (such as length of stay in an ED, or re-visits or readmissions to the ED) or provider satisfaction. Two independent reviewers screened the identified articles independently, and those included in the final analysis were assessed for quality and bias using the Newcastle-Ottawa Scale. RESULTS: Overall, 2535 articles were reviewed and 8 studies with a total of 728 children were included in the final analysis. Seven studies investigated the primary outcome of interest, practice variation in urine collection methods to diagnose a UTI. The seven studies that investigated novel methods of urine collection concluded that there were improved health care outcomes compared to conventional methods. Novel methods include emerging methods that are not captured yet captured in clinical practice guidelines including the use of ultrasound guidance to aid existing techniques. Three studies which investigated healthcare provider satisfaction found preference to novel methods of urine collection. CONCLUSIONS: There is significant practice variation in the urine collection methods within and between countries. Further research is needed to better examine practice variation among clinicians and adherence to national organizations and societies guidelines. PROSPERO registration number CRD42021267754.


Asunto(s)
Infecciones Urinarias , Toma de Muestras de Orina , Humanos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Toma de Muestras de Orina/métodos , Lactante , Control de Esfínteres , Preescolar , Pautas de la Práctica en Medicina , Niño
4.
J Vet Pharmacol Ther ; 47(3): 168-174, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38420879

RESUMEN

The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose-bred Beagles and four healthy client-owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client-owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23-3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half-life was similar for the Beagles and the Pug, 0.75-1.39 h, whereas the half-life was 1.70-1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild-type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6-12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple-dose regimens) before considering clinical trials or breed-specific differences.


Asunto(s)
Antibacterianos , Enfermedades de los Perros , Tianfenicol , Tianfenicol/análogos & derivados , Infecciones Urinarias , Animales , Perros , Tianfenicol/orina , Tianfenicol/farmacocinética , Tianfenicol/uso terapéutico , Tianfenicol/administración & dosificación , Masculino , Infecciones Urinarias/veterinaria , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/orina , Antibacterianos/orina , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/orina , Semivida
5.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38928323

RESUMEN

While urinary polymerase chain reaction (PCR) testing is effective in organism identification in patients with complex urinary tract infections (cUTI), limited data exists on the clinical usefulness of this test. We serially surveyed physicians treating symptomatic patients with cUTI both at presentation and after PCR, and urine culture (UC) results were available to ascertain how the test results modified the therapy. A total of 96 unique surveys completed by 21 providers were included in the data analysis. The mean age for female and male patients was 69.4 ± 15.5 and 71.6 ± 12.7 years, respectively. The test positivity and line-item concordance for UC and PCR were consistent with prior reports. The PCR results modified or confirmed treatment in 59/96 (61.5%) and 25/96 (26.0%) of the cases, respectively, with 12/29 (41.4%) and 47/67 (70.1%) having negative and positive PCR results, respectively, resulting in treatment change (difference 28.7%, p < 0.01). Of these, 55/59 (57.3%) were alterations in the antibiotic regimen. PCR use to modify treatment was similar across providers and not statistically different when stratified by patient age, gender, or prior empiric therapy. In 31/59 (52.5%) of the cases, the PCR results modified the treatment where UC would not; conversely, UC would have modified the treatment in 3/37 (8.1%) of the cases where PCR did not (difference 44.4%, p < 0.01). We find that PCR test results are used by clinicians in managing cUTI, and use of this test provides an opportunity to improve antibiotic stewardship in this difficult-to-treat subset of patients.


Asunto(s)
Toma de Decisiones Clínicas , Reacción en Cadena de la Polimerasa , Infecciones Urinarias , Humanos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/orina , Infecciones Urinarias/microbiología , Femenino , Masculino , Anciano , Reacción en Cadena de la Polimerasa/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Urinálisis/métodos
6.
J Pediatr ; 258: 113394, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37001635

RESUMEN

OBJECTIVE: To compare the accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and leukocyte esterase (LE) for the diagnosis of urinary tract infection (UTI) in children. STUDY DESIGN: We performed a systematic review and individual patient data meta-analysis of studies that examined urine NGAL as a marker of UTI in children <18 years of age. We created a standardized definition of UTI and applied it to all included children. We compared sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of NGAL with LE. RESULTS: We included individual patient data from 3 studies for a total of 845 children. Included children had a mean age of 0.9 years (SD, 0.6 years). Using a cutoff of 32.7 ng/mL, NGAL had a sensitivity of 90.3% (95% CI: 83.2%-95.0%) and specificity of 93.7% (95% CI: 91.7%-95.4%) for the diagnosis of UTI. LE, using a cutoff of ≧ trace had a sensitivity of 81.1% (95% CI: 72.5%-87.9%) and specificity of 97.0% (95% CI: 95.4%-98.1%). The AUC for NGAL was 0.95 (95% CI: 0.92-0.98). The AUC for LE was 0.90 (95% CI: 0.86-0.93). CONCLUSION: In young, febrile children, urinary NGAL is more sensitive for the diagnosis of UTI than LE but is slightly less specific.


Asunto(s)
Fiebre , Infecciones Urinarias , Humanos , Lactante , Biomarcadores/orina , Esterasas/orina , Fiebre/diagnóstico , Fiebre/etiología , Fiebre/orina , Lipocalina 2/orina , Curva ROC , Infecciones Urinarias/complicaciones , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina
7.
Eur J Clin Pharmacol ; 79(8): 1043-1049, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37266591

RESUMEN

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.


Asunto(s)
Insuficiencia Renal , Infecciones Urinarias , Humanos , Femenino , Anciano , Nitrofurantoína/efectos adversos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/inducido químicamente , Infecciones Urinarias/orina , Protocolos Clínicos , Insuficiencia Renal/tratamiento farmacológico , Riñón/fisiología , Antiinfecciosos Urinarios/efectos adversos , Antibacterianos/efectos adversos
8.
Pediatr Nephrol ; 38(10): 3337-3346, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37074426

RESUMEN

BACKGROUND: To determine whether urine neutrophil gelatinase-associated lipocalin (uNGAL) might be superior to pyuria for detecting urinary tract infection (UTI) regardless of urine specific gravity (SG) in young children. METHODS: We conducted a retrospective analysis of children aged < 3 years who were evaluated for UTI with urinalysis, urine culture, and uNGAL measurements during a 5-year period. Sensitivity, specificity, likelihood ratios (LRs), predictive values (PVs), area under the curves (AUCs) of uNGAL cut-off levels, and various microscopic pyuria thresholds for detecting UTI were calculated for dilute (SG < 1.015) and concentrated urine (SG ≥ 1.015). RESULTS: Of 456 children included, 218 had UTI. The diagnostic value of urine white blood cell (WBC) concentration to define UTI changed with urine SG. For detecting UTI, uNGAL cut-off of 68.4 ng/mL had higher AUC values than pyuria ≥ 5 WBCs/high power field (HPF) for dilute and concentrated urine samples (both P < 0.05). Positive LR and PV and specificity of uNGAL were all greater than those of pyuria ≥ 5 WBCs/HPF regardless of urine SG, although the sensitivity of pyuria ≥ 5 WBCs/HPF was higher than that of uNGAL cut-off for dilute urine (93.8% vs. 83.5%) (P < 0.05). At uNGAL ≥ 68.4 ng/mL and ≥ 5 WBCs/HPF, posttest probabilities of UTI were 68.8% and 57.5% for dilute urine and 73.4% and 57.3% for concentrated urine, respectively. CONCLUSIONS: Urine SG can affect the diagnostic performance of pyuria for detecting UTI and uNGAL might be helpful for identifying UTI regardless of urine SG in young children. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Piuria , Infecciones Urinarias , Niño , Preescolar , Humanos , Lipocalina 2 , Piuria/diagnóstico , Estudios Retrospectivos , Gravedad Específica , Urinálisis , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina
9.
Acta Paediatr ; 112(3): 550-556, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36463432

RESUMEN

AIM: To describe the urine collection methods used in precontinent children presenting at the Paediatric Emergency Department (PED) and compare results and contamination rates. METHODS: Retrospective observational cohort study that included 1678 urine cultures collected in infants <24 months of age between January 2016 and December 2019. Urine cultures were compared based on collection technique, sex and patient age. RESULTS: In total, 60.4% of samples were collected by clean-catch urine collection (CCUC), 26.4% by urethral catheterisation (UC) and 13.2% by urine bag (UB). Contamination rates were 2.9% (95% CI 1.3, 4.4) for UC, 11.3% (95% CI 9.3, 13.2) for CCUC and 23.4% (95% CI 17.8, 29.0) for UB. Significant differences in contamination rates were found between UC and CCUC in the 6-12-month age group (1.9% [95% CI 0.0-4.0] versus 12.0% [95% CI 7.2-16.8] [p < 0.0009]), and between UC and UB for all ages. CONCLUSIONS: CCUC is the most common method for urine culture collection in infants <24 months of age at the PED in our centre. UC has the lowest contamination rates, but significant differences were only observed between CCUC and UC in the 6-12-month age group. CCUC is a non-invasive alternative for urine collection in infants.


Asunto(s)
Infecciones Urinarias , Toma de Muestras de Orina , Lactante , Humanos , Niño , Toma de Muestras de Orina/métodos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Estudios Retrospectivos , Urinálisis , Servicio de Urgencia en Hospital
10.
Crit Rev Clin Lab Sci ; 59(2): 112-124, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34663175

RESUMEN

Urinalysis is considered the world's oldest laboratory test. Today, many laboratories use macroscopic urinalysis as a screening tool to determine when to subject urine samples for a microscopic urinalysis and/or bacterial culture. While reflexive urine microscopy has been practiced for decades, and reflexive urine culture, more recently, evidence-based guidelines regarding optimal reflexive criteria and workflows are lacking. Standard approaches are hindered, in part, by a lack of harmonization of urinalysis and urine culture practices, heterogeneity in patient populations that are studied, and lack of provider adherence to recommended practices. This review summarizes studies that have evaluated the performance of reflexive urine microscopy and reflexive urine culture, particularly in the context of urinary tract infections. It also examines reported clinical outcomes from reflexive urinalysis interventions and their impact on antibiotic stewardship efforts. Finally, it discusses laboratory operational considerations for the implementation of reflexive algorithms.


Asunto(s)
Urinálisis , Infecciones Urinarias , Femenino , Humanos , Masculino , Microscopía , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina
11.
Anal Bioanal Chem ; 414(2): 847-865, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34668042

RESUMEN

Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material's portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products.


Asunto(s)
Papel , Infecciones Urinarias/diagnóstico , Bacterias/aislamiento & purificación , Celulosa , Colorimetría/métodos , Medios de Cultivo , Técnicas Electroquímicas/métodos , Hongos/aislamiento & purificación , Humanos , Dispositivos Laboratorio en un Chip , Productos para la Higiene Menstrual , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina
12.
Pediatr Nephrol ; 37(2): 385-391, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34272611

RESUMEN

BACKGROUND: Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. METHODS: In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. RESULTS: BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). CONCLUSIONS: BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI.


Asunto(s)
Piuria , Infecciones Urinarias , Biomarcadores , Niño , Humanos , Recuento de Leucocitos , Piuria/diagnóstico , Urinálisis/métodos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Orina
13.
Pediatr Nephrol ; 37(1): 171-177, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34251495

RESUMEN

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Fiebre , Infecciones Urinarias , Biomarcadores/orina , Estudios de Casos y Controles , Quimiocina CCL3/orina , Niño , Estudios Transversales , Fiebre/orina , Humanos , Interleucina-8/orina , Lipocalina 2/orina , Estudios Prospectivos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina
14.
Mol Cell Proteomics ; 19(3): 456-466, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31896675

RESUMEN

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.


Asunto(s)
Proteoma , Infecciones Urinarias/orina , Reflujo Vesicoureteral/orina , Femenino , Humanos , Masculino , Péptidos/orina , Proyectos Piloto , Recurrencia , Infecciones Urinarias/metabolismo , Orina/química , Reflujo Vesicoureteral/metabolismo
15.
Proc Natl Acad Sci U S A ; 116(37): 18738-18744, 2019 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-31451660

RESUMEN

High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing, however, does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Here, we explore the utility of high-throughput sequencing of cell-free DNA (cfDNA) after bisulfite conversion to map the tissue and cell types of origin of host-derived cfDNA, and to profile the bacterial and viral metagenome. We applied this assay to 51 urinary cfDNA isolates collected from a cohort of kidney transplant recipients with and without bacterial and viral infection of the urinary tract. We find that the cell and tissue types of origin of urinary cfDNA can be derived from its genome-wide profile of methylation marks, and strongly depend on infection status. We find evidence of kidney and bladder tissue damage due to viral and bacterial infection, respectively, and of the recruitment of neutrophils to the urinary tract during infection. Through direct comparison to conventional metagenomic sequencing as well as clinical tests of infection, we find this assay accurately captures the bacterial and viral composition of the sample. The assay presented here is straightforward to implement, offers a systems view into bacterial and viral infections of the urinary tract, and can find future use as a tool for the differential diagnosis of infection.


Asunto(s)
Ácidos Nucleicos Libres de Células/aislamiento & purificación , Interacciones Huésped-Patógeno/genética , Metagenoma/genética , Metagenómica/métodos , Complicaciones Posoperatorias/diagnóstico , Infecciones Urinarias/diagnóstico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/orina , Biomarcadores/orina , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/orina , Metilación de ADN/genética , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/orina , ADN Viral/genética , ADN Viral/aislamiento & purificación , ADN Viral/orina , Diagnóstico Diferencial , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno/inmunología , Humanos , Riñón/citología , Riñón/inmunología , Riñón/microbiología , Riñón/patología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Masculino , Infiltración Neutrófila/inmunología , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/orina , Receptores de Trasplantes , Vejiga Urinaria/citología , Vejiga Urinaria/inmunología , Vejiga Urinaria/microbiología , Vejiga Urinaria/patología , Infecciones Urinarias/inmunología , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina , Virosis/diagnóstico , Virosis/inmunología , Virosis/orina , Virosis/virología
16.
Am Fam Physician ; 106(1): 27-35B, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35839369

RESUMEN

Comprehensive urinalysis involves inspection of the urine, dipstick chemical analysis, and microscopy and can be performed in the office setting. When testing for urinary tract infection, midstream urine should be collected using the clean-catch technique. A urine collection bag specimen can be used for clinically stable febrile infants with suspected urinary tract infection; however, the presence of leukocyte esterase or nitrites warrants more invasive urine collection. Urine specific gravity shows hydration status. Urinary pH levels can indicate diet, metabolism, or the presence of stones. Bilirubin and urobilinogen may suggest hepatobiliary disease or hemolysis. Glucosuria often indicates uncontrolled diabetes mellitus, and ketones suggest illness and inadequate nutrition. Hematuria on dipstick testing can be confirmed in the office using a spun urine sample. Proteinuria on dipstick testing should be followed by a quantitative test such as a spot urine albumin/creatinine ratio. In patients with symptoms of a urinary tract infection, the presence of nitrites is more specific for bacterial infection, and a positive leukocyte esterase result may occur from inflammation and infection. Asymptomatic bacteriuria is often unnecessarily treated in older patients. Without symptoms of urinary tract infection, urine culture is useful only in pregnancy and preparation for endoscopic urologic procedures.


Asunto(s)
Bacteriuria , Infecciones Urinarias , Anciano , Bacteriuria/diagnóstico , Femenino , Hematuria , Humanos , Lactante , Nitritos/orina , Embarazo , Sensibilidad y Especificidad , Urinálisis/métodos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina
17.
Sensors (Basel) ; 23(1)2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36616986

RESUMEN

Bacterial infections can affect the skin, lungs, blood, and brain, and are among the leading causes of mortality globally. Early infection detection is critical in diagnosis and treatment but is a time- and work-consuming process taking several days, creating a hitherto unmet need to develop simple, rapid, and accurate methods for bacterial detection at the point of care. The most frequent type of bacterial infection is infection of the urinary tract. Here, we present a wireless-enabled, portable, potentiometric sensor for E. coli. E. coli was chosen as a model bacterium since it is the most common cause of urinary tract infections. The sensing principle is based on reduction of Prussian blue by the metabolic activity of the bacteria, detected by monitoring the potential of the sensor, transferring the sensor signal via Bluetooth, and recording the output on a laptop or a mobile phone. In sensing of bacteria in an artificial urine medium, E. coli was detected in ~4 h (237 ± 19 min; n = 4) and in less than 0.5 h (21 ± 7 min, n = 3) using initial E. coli concentrations of ~103 and 105 cells mL-1, respectively, which is under or on the limit for classification of a urinary tract infection. Detection of E. coli was also demonstrated in authentic urine samples with bacteria concentration as low as 104 cells mL-1, with a similar response recorded between urine samples collected from different volunteers as well as from morning and afternoon urine samples.


Asunto(s)
Escherichia coli , Infecciones Urinarias , Humanos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina , Bacterias
18.
Appl Environ Microbiol ; 87(16): e0074421, 2021 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-34105987

RESUMEN

Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBCs), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI.


Asunto(s)
Proteínas Bacterianas/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Infecciones Estafilocócicas/microbiología , Infecciones Urinarias/microbiología , Orina/microbiología , Animales , Adhesión Bacteriana , Proteínas Bacterianas/metabolismo , Eritrocitos/microbiología , Regulación Bacteriana de la Expresión Génica , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/fisiología , Ovinos , Transcriptoma , Infecciones Urinarias/orina , Virulencia
19.
J Urol ; 206(6): 1482-1489, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34288716

RESUMEN

PURPOSE: Reliable urine samples are of eminent importance when diagnosing urinary tract infections (UTIs) in children. Noninvasive procedures are convenient but likely to be contaminated. This study aimed to compare the diagnostic accuracy of urine samples obtained by the midstream clean-catch method (CCU) to urine obtained by suprapubic aspiration (SPA) and to evaluate the ability of urinary dipstick to predict true infection. MATERIALS AND METHODS: Retrospectively, data on children <2 years of age seen at our center for suspicion of UTI who had a CCU and a SPA performed the same day were included. Any growth in SPA was considered significant, whereas for CCU we tested 2 cutoff values of 104 and 105 CFU/ml, along with urinary dipstick results. RESULTS: A total of 223 children were included. Using a cutoff of ≥104 CFU/ml, 16.6% of the cohort (37 cases) would be misdiagnosed if relying only on CCU. Using ≥105 CFU/ml, the rate was 24.6% (55 cases). Evaluating leukocyte esterase on urinary dipstick, a large difference between using CCU (sensitivity 94.7%, specificity 14.4%) and SPA (sensitivity 78.9%, specificity 82.2%) became obvious. CONCLUSIONS: A large number of children will be misdiagnosed if relying on CCU specimens compared to SPA. Relying on a negative leukocyte esterase dipstick test to rule out a UTI is not sufficient in a child with high suspicion of such an infection. SPA is a safe procedure, and we thus recommend its use to avoid delay of treatment and unnecessary invasive followup investigations.


Asunto(s)
Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Toma de Muestras de Orina/métodos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Succión
20.
World J Urol ; 39(5): 1559-1567, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32661555

RESUMEN

OBJECTIVE: To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications. METHODS: We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points. RESULTS: Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525-11.569; p = 0.006). CONCLUSION: A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.


Asunto(s)
Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/orina , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria , Reservorios Urinarios Continentes/fisiología , Infecciones Urinarias/epidemiología , Infecciones Urinarias/orina , Cistectomía , Humanos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Urinálisis
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