Quantitative urinary tract infection diagnosis of leukocyte esterase with a microfluidic paper-based device.

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-µPADs and LE-Ag-ZnO-µPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl-l-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL-1), i.e. ≈12 to 108 µg L-1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL-1). The lower concentrations of LE detectable by LE-Ag-µPADs (1-8 × 5.2 U mL-1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser.

Diagnostic Accuracy of Point-of-care Nitrite and Leukocyte Esterase Dipstick Test for the Screening of Pediatric Urinary Tract Infections.

Our study aimed to evaluate the diagnostic performance of point-of-care nitrite and leukocyte esterase (LE) dipsticks in the diagnosis of suspected urinary tract infection (UTI) in infants <6 months (young infants) versus older children. The secondary objectives were to study the dipstick efficacy in children with congenital anomalies of the kidney and urinary tract (CAKUT) versus those without CAKUT; in children with simple UTI versus complicated UTI; and to evaluate the clinico-microbiological profile of children presenting with UTI. In this prospective observational study, cases with suspected UTI were enrolled from pediatric emergency or outpatient departments. Urine was collected for performing the urine dipstick and culture. Descriptive data regarding CAKUT, age, gender, etc., were recorded in a predesigned pro forma. We screened 506 children with suspected UTI, of whom 221 had urine culture positive. Approximately 38.4% of the children with UTI had underlying CAKUT, while 7.6% had renal scars. The most common CAKUT was vesicoureteric reflux (VUR). About 12 patients (2.3%) were known to have CAKUT at the time of enrollment in the study. In infants <6 months, LE dipstick had sensitivity 92%, specificity 89.7%, positive predictive value (PPV) 86.7%, negative predictive value (NPV) 93.8%, likelihood ratio (LR) + 8.9, LR- 0.09. In infants <6 months, nitrite dipstick had sensitivity 38%, specificity 97%, PPV 90.4%, NPV 68%, LR+ 12.6 and LR-0.63. In the age group 6 months to 12 years, the efficacy was better for both dipsticks. In age group more than 6 months to 12 years, LE dipstick had sensitivity 96.4%, specificity 95.8%, PPV 94.8 %, NPV 97.2%, LR+ 22.9, LR- 0.04. In age group more than six months to 12 years, nitrite dipstick had sensitivity 94.7%, specificity 99.5%, PPV 99.3%, NPV 96%, LR+ 189.4, and LR-0.05.

Predicting Urinary Tract Infections With Interval Likelihood Ratios.

BACKGROUND: Protocols for diagnosing urinary tract infection (UTI) often use arbitrary cutoff values of urinalysis components to guide management. Interval likelihood ratios (ILRs) of urinalysis results may improve the test's precision in predicting UTIs. We calculated the ILR of urinalysis components to estimate the posttest probabilities of UTIs in young children. METHODS: Review of 2144 visits to the pediatric emergency department of an urban academic hospital from December 2011 to December 2019. Inclusion criteria were age <2 years and having a urinalysis and urine culture sent. ILR boundaries for hemoglobin, protein, and leukocyte esterase were "negative," "trace," "1+," "2+" and "3+." Nitrite was positive or negative. Red blood cells and white blood cells (WBCs) were 0 to 5, 5 to 10, 10 to 20, 20 to 50, 50 to 100, and 100 to 250. Bacteria counts ranged from negative to "loaded." ILRs for each component were calculated and posttest probabilities for UTI were estimated. RESULTS: The UTI prevalence was 9.2%, with the most common pathogen being Escherichia coli (75.2%). The ILR for leukocyte esterase ranged from 0.20 (negative) to 37.68 (3+) and WBCs ranged from 0.24 (0-5 WBCs) to 47.50 (100-250 WBCs). The ILRs for nitrites were 0.76 (negative) and 25.35 (positive). The ILR for negative bacteria on urinalysis was 0.26 and 14.04 for many bacteria. CONCLUSIONS: The probability of UTI in young children significantly increases with 3+ leukocyte esterase, positive nitrite results, 20 to 50 or higher WBCs, and/or many or greater bacteria on urinalysis. The probability of UTI only marginally increases with trace or 1+ leukocyte esterase or 5 to 20 WBCs. Our findings can be used to more accurately predict the probability of true UTI in children.

Midstream urine sampling is necessary for accurate measurement of the urinary level of neutrophil gelatinase-associated lipocalin in healthy female subjects.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin is an established biomarker of acute kidney injury, however, the levels are affected by the number of white blood cells in the urine. As we suspected the portion of the urinary stream sampled could also have a significant influence on the urinary NGAL levels in female subjects, we investigated the influence of the urine sampling procedure on the urinary NGAL levels. METHODS: We collected 25-mL urinary specimens from each of initial-stream and midstream urinary specimens, including 28 healthy adult female volunteers without kidney diseases or UTI. Then we compared the WBC count, NGAL level, and creatinine level between these specimens. RESULTS: We observed that the urinary NGAL levels were significantly higher in the specimens obtained from initial-stream urinary samples than in midstream specimens, and that they were strongly correlated with the leukocyte esterase activity and WBC count. Moreover, the differences in the urinary NGAL levels between the initial- and midstream urine samples were greater for initial-stream samples with higher leukocyte esterase activities, with a significant difference even for the initial-stream samples with no detectable leukocyte esterase activity. CONCLUSION: Therefore, midstream urine sampling is strongly recommended for accurate measurement of the urinary NGAL levels.

Infection Screening in Biofluids with Glucose Test Strips.

The four glucosyl esters were synthesized and tested for the determination of infection enzyme leukocyte esterase (LE) in human synovial (joint) fluid and urine. The esters acted as LE substrates releasing glucose in a direct proportion to the activity of LE in a sample. The freed glucose was then detected by a coupled-enzyme assay at either a nitrogen-doped carbon nanotube (N-CNT) electrode or a commercial glucose test strip. The assays at the N-CNT electrode detected LE down to 0.81 nM (25 µg L-1) and showed the fastest kinetics (2.1 × 105 M-1 s-1) for esters with the least crowded space around their carbonyl group. When used with glucose strips, the esters discerned clinically relevant levels of LE up to at least 26 nM (800 µg L-1) in the microliter-sized samples of bodily fluids. The reading of glucose strips with a potentiostat, instead of a personal glucose meter (blood glucometer), shortened the time of required sample incubation from 3 h to 5 min. Correcting the signal of incubated sample for that of original sample eliminated matrix effects and accounted for the presence of native glucose. The new esters have a potential to extend the use of glucose strips (already used by millions for diabetes monitoring) to the quantification of the severity of urinary tract and periprosthetic joint infections.

Should the Absence of Urinary Nitrite Influence Empiric Antibiotics for Urinary Tract Infection in Young Children?

OBJECTIVES: Screening for urinary tract infection (UTI) includes urinary nitrite testing by dipstick urinalysis. Gram-negative enteric organisms produce urinary nitrite and represent the most common uropathogens. Enterococcus, a less common uropathogen, does not produce nitrite and has a unique antibiotic resistance pattern. Whether to adjust empiric antibiotics in the absence of urinary nitrite has not been established. Our primary objective was to determine prevalence of enterococcal UTI among young children with a nitrite negative urinalysis. METHODS: A retrospective study of children aged less than 2 years evaluated in the emergency department for possible UTI and had a paired urinalysis and urine culture was performed. Urinary tract infection was defined by catheterized culture yielding greater than or equal to 50,000 colony-forming units per milliliter of a single uropathogen. Prevalence of uropathogens among nitrite negative samples was studied. RESULTS: A total of 7599 children were studied. Median (interquartile range) age was 5.6 (2.3-11.2) months, and 57% were female. Prevalence of UTI was 8.1%. Enterococcus was the uropathogen in 2.1% of UTIs, and all cases had negative dipstick nitrite. Among nitrite negative UTIs, 95.6% of uropathogens were gram-negative and only 3.2% (confidence interval, 1.8%-5.3%) were enterococcus. None of the 200 UTIs with positive nitrite yielded enterococcus (upper confidence interval, 1.4%). Among children with positive leukocyte esterase and negative nitrite, only 0.7% of cases had enterococcal UTI. CONCLUSIONS: Only 3% of nitrite negative UTIs were caused by enterococcus. Given the low prevalence of enterococcal UTI, the absence of dipstick nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children.

Fast and Sensitive: Automated Point-of-Care Urine Dips.

OBJECTIVE: Point-of-care (POC) urine dipstick is a highly used test in the pediatric emergency department (PED) owing to its fast turn-around time and inexpensive cost. Past studies have shown hand-held urine dipsticks and automated urinalysis in children younger than 48 months to be sensitive predictors for urinary tract infection (UTI). It is hypothesized that POC dip testing is as accurate as laboratory urinalysis in the diagnosis of UTI. METHODS: A retrospective chart review was conducted on patients (aged birth through 18 years) presenting to a PED between January 2015 and December 2015. Eligible subjects included those that had a POC dip, laboratory urinalysis (lab UA), and urine culture performed during their PED visit. Subjects were selected, using a random number generator; 334 charts were selected. A positive POC dip was defined as having a positive leukocyte esterase or the presence of nitrites. A positive lab UA was defined as having a positive leukocyte esterase, nitrites, or greater than 10 white blood cells per high-power field. Urine culture was used as the criterion standard for comparison. RESULTS: A total of 334 subjects' charts were reviewed. Sensitivity and specificity of the POC dip were 91.4% (95% confidence interval [CI], 76.9%-98.2%) and 63.9% (95% CI, 57.2%-69.3%); lab UA, 91.4% (95% CI, 76.9%-98.2%) and 63.9% (95% CI, 58.2%-69.3%); and lab dip, 88.6% (95% CI, 73.3%-96.8%) and 65.6% (95% CI, 59.9%-70.9%). CONCLUSIONS: Point-of-care dips are as sensitive in detecting UTI as the lab UA. A prospective study could allow for further demographic evaluation of POC dip diagnosed UTI.

Squamous epithelial cell presence reduces accuracy of urinalysis for prediction of positive urine cultures.

BACKGROUND: Diagnostic value of urinalysis specimens contaminated with squamous epithelial cells (SEC) from the genital surfaces is assumed to be limited compared to clean-catch samples. However, no studies have quantified the change in predictive value in the presence of SECs for individual urinalysis markers. METHODS: In a retrospective, single center cohort study, we analyzed all urine cultures sent from the ED over a 26-month period with corresponding urinalysis results. Cultures were classified as positive with growth of >104 colony forming units of pathogenic bacteria, negative if no growth, or contaminated for all other results. UA specimens were classified as contaminated or clean based on SEC presence. Accuracy of urinalysis markers for prediction of positive cultures was calculated as an area under the curve (AUC) and was compared between contaminated and clean UA specimens. RESULTS: 6490 paired UA and urine cultures were analyzed, consisting of 3949 clean and 2541 contaminated samples. SEC presence was less common with male gender, older age, and smaller BMI. Urine cultures were 19.2% positive overall, and SECs were more common in contaminated cultures. AUCs for individual markers ranged from 0.557 to 0.796, with pyuria, bacteriuria, and leukocyte esterase having higher AUC in clean samples over contaminated. CONCLUSION: Analysis of AUC for individual urinalysis markers showed reduced diagnostic accuracy in the presence of SECs. SEC presence also reflected much higher rates of contaminated cultures. These results support the reduced reliance on contaminated UA specimens for ruling in UTI in ED patients.

Relationship between urinalysis findings and responsible pathogens in children with urinary tract infections.

BACKGROUND: Pyuria, presence of bacteria, leukocyte esterase, and nitrite positivity in urinalysis should be considered together, and simultaneous urine culture test should be performed in the diagnostic evaluation of urinary tract infection (UTI). The absence of pyuria in urinalysis cannot exclude UTI in patients with suggestive clinical findings. OBJECTIVE: It was aimed to assess relationship between urinalysis tests and uropathogen and to evaluate antibiotic resistance in children. METHODS: The study included patients (aged 0-18 years) with significant uropathogen growth in urine culture tests. The patients' data regarding age, gender, results of urine microscopy, urine culture, and antibiogram were recorded retrospectively. RESULTS: Overall, 705 patients (562 girls, 143 boys) with significant growth in urine culture test were included. Median age was 72 months among girls and 12 months among boys. Most common uropathogens were Escherichia coli (79.6%) and Klebsiella pneumoniae (8.2%). E. coli was more commonly among girls (87%) and Klebsiella spp. among boys (53.3%). Pyuria was positive in urinalysis in 75% of patients. Pyuria presence was more common in patients with E.coli or Proteus spp. (80.6% and 71.4%, respectively) than those with Enterococcus spp. and Klebsiella spp. (52.0% and 53.3%, respectively). In culture antibiogram tests, ampicillin resistance was 100% in Klebsiella oxytoca and Enterobacter spp. and 72% in E. coli strains. No ceftriaxone resistance was observed in K. oxytoca, Citrobacter spp., Pseudomonas aeruginosa, and Enterobacter spp. DISCUSSION: Most UTIs were seen in older girls. Pyuria might be lacking in UTIs associated to Klebsiella spp. and Enterococcus spp., and absence of pyuria may not exclude UTI in patients with compatible clinical findings. Ceftriaxone is still an option in empirical treatment; unnecessary use of third-generation cephalosporins should be avoided, particularly in infections other than UTI. CONLUSIONS: It was found that E. coli more commonly caused leukocyturia, leukocyte esterase positivity, and pyuria; that pyuria might be lacking in UTIs associated to Klebsiella spp. and Enterococcus spp. and that pyuria was more prevalent among girls. It is though that urine culture tests should be performed in children with suspected UTI even in the absence of pyuria because lack of pyuria may lead delay in diagnosis and treatment as well as renal scar formation.

Diagnostic value of dipstick test in adult symptomatic urinary tract infections: results of a cross-sectional Tunisian study.

Urinary tract infections (UTIs) are common. The diagnosis is confirmed by urine culture which is costly and takes at least 24 hours before results are known. The aim of this study was to determine the diagnostic accuracy of dipstick test for the diagnosis of UTI in symptomatic adult patients. We conducted a cross-sectional study in the department of Infectious Diseases, Sousse-Tunisia during a two-year period. We included all patients with clinical signs of UTI. Urine samples were tested for the presence of leukocyte esterase (LE) and nitrites. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LE and nitrites were calculated against urine culture as gold standard. Four hundred thirty one patients, 139 men (32%) and 292 women (68%) were included. One hundred sixty six patients (39%) had UTI. The most frequently isolated microorganism was Escherichia coli (75%). LE had a high sensitivity (87%) but a low specificity (64%), while nitrites had a high specificity (95%) but a low sensitivity (48%). Combined positive LE and nitrites had a high PPV (85%) and combined negative LE and nitrites had a high NPV (92%), while positive LE combined with negative nitrites had a low PPV (47%) and a low NPV (53%). In conclusion, in adult patients with UTI symptoms, an alternate diagnosis should be considered if the LE is negative, while an early empirical antibiotic therapy against Enterobacteriaceae should be started if the nitrites are positive.

Current practice on the management of pre-operative urine dipstick results in women undergoing gynaecological surgery in Wales.

A survey was circulated to consultant gynaecologists across Wales, to evaluate the management of pre-operative urine dipstick results. Questions were based on NICE guideline 171, regarding the management of urinary incontinence in women. Six respondents never checked their patient's urine dipstick results. Of the remaining 37 respondents, 70% always check and 30% sometimes check. Overall, 37.1% cancelled surgery when a urine dipstick was positive for either nitrite or leukocyte-esterase (LE). A significantly larger proportion cancelled surgery when symptomatic for urinary tract infection (p< 0.001), and when nitrite and LE positive compared to only LE positive (p< 0.05). This survey provides evidence that gynaecological operations are potentially being cancelled unnecessarily based on a screening test with limited sensitivity and specificity. Further research is needed into the outcomes of gynaecological surgery in women symptomatic of urinary tract infection to provide guidance on the use of pre-operative urinalysis and the management of test results. Impact statement What is already known on this subject? The strongest risk factor for postoperative urinary tract infections (UTIs) is a pre-operative recurrent UTI (Nygaard et al. 2011 ). This is the reason behind the urine dipstick being part of the pre-operative checklist for gynaecological surgery. Traditionally, a suspected UTI would mean postphoning surgery whilst treating the UTI. It is known that the sensitivity of the nitrite test and leukocyte-esterase test when used alone is low and cannot rule out UTI in most patients (Mambatta et al. 2015 ). Urine culture is therefore suggested for all patients with a suspected UTI (John et al. 2006 ). To our knowledge, there are no data available on whether we should be postphoning gynaecological surgery based on a urine dipstick result. What the results of this study add? Overall, 37.1% of respondents cancelled surgery when a pre-operative urine dipstick was positive for either nitrite or leukocyte-esterase. This provides evidence of variation in the practice of using the urine dipstick in women undergoing gynaecological surgery in Wales. These cancellations are potentially unnecessarily. Furthermore, 14% of respondents did not use a urine dipstick and the majority did not act on an abnormal results, implying clinicians have a low confidence in the test as a screening tool. What the implications are of these findings for clinical practice and/or further research? We propose removing the urine dipstick as a pre-operative screening test. Asymptomatic bacteriuria is common in women and routine screening for UTI pre-operatively will therefore inevitably lead to unnecessary intervention (i.e. cancellation). Further research is needed into the outcomes of gynaecological surgery in women symptomatic of UTI to be able to provide guidance on the use of pre-operative urinalysis and management of the test results.

[Urinary cultures fall short in institutionalized elderly patients]. / Urinekweken in verpleeghuis schieten tekort.

The diagnosis of urinary tract infections (UTI) in institutionalized elderly patients is complex, due to vague symptomatology. Moreover, the high prevalence of asymptomatic bacteriuria (ABU) is often ignored in clinical decision making, leading to a vast overprescription of antibiotics. Pragmatic clinical guidelines have been published to reduce the ordering of urinary cultures and prescription of antibiotics. Nitrite and leukocyte esterase dipstick tests have a high negative predictive value. Urinary cultures should only be ordered to guide antibiotic therapy after said decision has been taken based on clinical grounds. Apart from these pragmatic recommendations, current research is focussing on pathogen as well as host-derived factors. A smart combination of virulence factors and detection of immunological biomarkers could help clinicians to decide whether antibiotics should be initiated or not.

Semiquantitative, fully automated urine test strip analysis.

OBJECTIVES: Urinalysis is one of the most frequently ordered diagnostic laboratory tests. In order to reduce workload and costs, rapid screening tests such as urine test strip analyses are applied. The aim of this study was to evaluate the analytical performance of the UC-3500 as well as the diagnostic performance in comparison with reference methods. DESIGN AND METHODS: We measured within-run and between-run imprecision based on quantitative reflectance values. 347 prospectively included urine specimens were investigated for the presence of glucose, protein, albumin, leukocyte esterase, and hemoglobin peroxidase activity, and ordinal scale results were compared to an automated urine particle analyzer (UF-5000, Sysmex, Kobe, Japan) and wet chemistry (Roche Cobas 8000, Mannheim, Germany). RESULTS: Within-run and between-run imprecision results based on reflectance data for both the 9 and 11 parameter test strips ranged from 0.07% to 1.36% for the low-level control and from 0.37% to 6.13% for the high-level control, depending on the parameter. Regarding diagnostic performance, the sensitivity/specificity for glucose, protein, albumin, leukocyte esterase, and hemoglobin peroxidase was 100/60%, 94.2/88.2%, 81.8/89.2%, 81.7/92.8%, and 85.1/88.6%, respectively; the negative predictive value was 100%, 83.3%, 89.1%, 94.6%, and 96.1%. The Spearman correlation coefficients of the UC-3500 vs reference methods ranged from 0.915 to 0.967, depending on the parameter. CONCLUSION: This fully automated urine test strip analyzer overall shows a satisfying performance and can reliably screen out negative urine samples in order to focus on further characterization of positive samples in the following steps of the workflow.

Which Objective Parameters Are Associated with a Positive Urine Culture in the Setting of Ureteral Calculi: The Ureteral Calculi Urinary Culture Calculator.

OBJECTIVE: To determine associations between laboratory values and subsequent culture positivity in the acute ureteral calculi patient. Specifically, we aim to develop a predictive model to assist with optimization of patient outcomes and improvement of antimicrobial stewardship. METHODS: Utilizing the electronic medical record system, we conducted a retrospective review of 3888 patients with ureteral calculi. Relevant demographic information, vital signs, and laboratory parameters obtained in the emergency department were tabulated. We applied a combination of analysis of variance and Pearson Fisher's Exact test for the analysis. RESULTS: A total of 3888 patients were included in the analysis of whom 3171 (81.6%) had a negative urine culture and 717 (18.4%) had a positive urine culture. Basic vital signs and laboratory parameters, such as heart rate, temperature, white blood cell (WBC) count, platelet count, and neutrophil differential only varied slightly in the positive and negative culture groups. Urinary nitrite was found to have specificity of 97.2% with a negative predictive value of 83.7%. Urinary leukocyte esterase was found to have a sensitivity of 86.8% and positive predictive value of 46.9%. On microscopy analysis, WBCs per high power field (WBCs/hpf) varied directly with likelihood of a positive urine culture; >150 WBCs/hpf had an 86.1% likelihood of positive urine culture. CONCLUSION: With the data provided from this large cohort analysis, we were able to create the ureteral calculi urinary culture calculator. With this calculator, urologists are better equipped to stratify a patient's risk of having a positive urine culture in the setting of a ureteral calculus.

No need for a urine culture in elderly hospitalized patients with a negative dipstick test result.

To determine the clinical utility/disutility of canceling urine cultures in elderly patients with a negative dipstick. The cohort included consecutive patients aged ≥ 65 years hospitalized in internal medicine departments with an admission urinalysis and urine culture (January 1, 2014 to December 31, 2016). We calculated the sensitivity of the dipstick (either a trace leukocyte esterase or a positive nitrite test result) to detect patients with bacteriuria, and the decrease in urine cultures resulting from cancelation in patients with a negative dipstick. We reviewed the charts of patients with a positive culture but negative dipstick to determine if they received appropriate antibiotic therapy and if the culture results had clinical utility, defined as changes in antibiotic therapy made according to culture results in a patient who did not respond to initial antibiotic therapy. The sensitivity of the dipstick for bacteriuria was 90.8% (95% CI, 89.6-92.0%). Of the 210 patients with a positive culture but negative dipstick, 132 (62.9%) had a diagnosis clearly outside the urinary tract. Thirty-five patients (16.7%) received inappropriate differential antibiotic therapy. Urine cultures did not have clinical utility and canceling urine cultures in those with a negative dipstick would result in a 41.5% (95% CI, 40.3-42.7%) decrease in urine cultures. We conclude that canceling orders for urine cultures in the elderly patient with a negative dipstick did not have clinical disutility and would decrease inappropriate antibiotic therapy. Extrapolation to other settings is dependent on urinalysis methodology, patient selection, and physician ordering and treatment behaviors.

Uropathogens and Pyuria in Children With Neurogenic Bladders.

: media-1vid110.1542/5727212324001PEDS-VA_2017-3006Video Abstract BACKGROUND: A recent study revealed that specific uropathogens are associated with lower odds of pyuria in a general pediatrics population. Children with neurogenic bladders who require clean intermittent catheterization (CIC) frequently have pyuria. Our objective with this study was to determine if an association exists between pyuria and type of uropathogen in CIC-dependent children. METHODS: We obtained urinalysis and urine culture results from electronic medical records from January 2008 through December 2014 for patients ≤18 years of age with neurogenic bladders managed at a single institution. Cultures without concurrent urinalyses were excluded from analysis, as were cultures that yielded no growth, fungal growth, or growth of unidentified mixed organisms. We used logistic regression to determine the association of pyuria and leukocyte esterase with specific uropathogens. RESULTS: We included 2420 cultures in this analysis. The growth of Enterococcus on urine culture was associated with lower odds of both pyuria and leukocyte esterase. In contrast, the growth of more than 100 000 colony-forming units per milliliter of Proteus mirabilis was associated with increased odds of both pyuria and leukocyte esterase, and the growth of Pseudomonas aeruginosa was associated with increased odds of leukocyte esterase but not pyuria. Certain etiologies of neurogenic bladder, such as bladder exstrophy and cloacal malformations, were also associated with increased odds of pyuria compared with neurogenic bladder due to myelomeningocele. CONCLUSIONS: In children with neurogenic bladders who require CIC, Enterococcus may grow in urine culture without pyuria or positive leukocyte esterase. Accordingly, urine cultures should be obtained in symptomatic children, regardless of urinalysis results.

The Leukocyte Esterase Test Strip Is a Poor Rule-Out Test for Periprosthetic Joint Infection.

BACKGROUND: The urinary leukocyte esterase (LE) test strip has been suggested as a good screening test for periprosthetic joint infection (PJI). The purpose of this study is to compare the diagnostic profile of LE assays from different manufacturers and determine whether the LE test strip is a good rule-out test. METHODS: Synovial fluid samples (N = 344), sent to 1 laboratory for PJI testing, were used in this prospective study. Four different tests for synovial fluid LE were simultaneously evaluated for their performance in detecting white blood cell (WBC) positive samples (>3000 cells/µL). RESULTS: Both neutrophil elastase immunoassays demonstrated greater sensitivity than urinary LE test strips (92.0% and 90.8% vs 72.4% and 80.3%; all P < 0.011). Fifty-three percent of false-negative urinary LE test strip results clearly missed the presence of elevated levels of synovial fluid LE. Invalid urinary LE test strip results were 4-fold more likely among WBC (+) compared with WBC (-) samples (27.0% vs 6.8%; P < 0.0001). The combined failure to detect an elevated WBC count, because of either false-negative or invalid results, was 47.1% and 41.4% for the Roche and Siemens test strips, respectively. CONCLUSIONS: This study agrees with the existing literature demonstrating that the LE test strips are among the lowest sensitivity tests for PJI. The urinary LE tests strips should not be used to rule-out PJI, as they often fail to detect abundant levels of LE in synovial fluid. Instead, it is more appropriate to use the (++) LE test strip result as a secondary confirmatory rule-in test for PJI because of its high specificity.

Quantitative urine test strip reading for leukocyte esterase and hemoglobin peroxidase.

BACKGROUND: Recently, urine test strip readers have become available for automated test strip analysis. We explored the possibilities of the Sysmex UC-3500 automated urine chemistry analyzer based on complementary metal oxide semiconductor (CMOS) sensor technology with regard to accuracy of leukocyte esterase and hemoglobin peroxidase results. We studied the influence of possible confounders on these measurements. METHODS: Reflectance data of leukocyte esterase and hemoglobin peroxidase were measured using CMOS technology on the Sysmex UC-3500 automated urine chemistry analyzer. Analytical performance (imprecision, LOQ) as well as the correlation with white blood cell (WBC) and red blood cell (RBC) counts (Sysmex UF-5000) were studied. Furthermore, the influence of urinary dilution, haptoglobin, pH and ascorbic acid as confounders was determined. RESULTS: Within- and between-run imprecision (reflectance signal) ranged from 1.1% to 3.6% and 0.9% to 4.2% for peroxidase and 0.4% to 2.5% and 0.4% to 3.3% for leukocyte esterase. Good agreement was obtained between the UF-5000 for RBCs and peroxidase reflectance (r=0.843) and for WBCs and leukocyte esterase (r=0.821). Specific esterase activity decreased for WBC counts exceeding 100 cells/µL. Haptoglobin influenced the peroxidase activity, whereas leukocyte esterase and peroxidase activities showed a pH optimum between 5.0 and 6.5. A sigmoidal correlation was observed between urinary osmolality and peroxidase activity. CONCLUSIONS: CMOS technology allows to obtain high quality test strip results for assessing WBC and RBC in urine. Quantitative peroxidase and leukocyte esterase are complementary with flow cytometry and have an added value in urinalysis, which may form a basis for expert system development.

Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60 Days and Younger.

OBJECTIVES: Reports of the test accuracy of the urinalysis for diagnosing urinary tract infections (UTIs) in young febrile infants have been variable. We evaluated the test characteristics of the urinalysis for diagnosing UTIs, with and without associated bacteremia, in young febrile infants. METHODS: We performed a planned secondary analysis of data from a prospective study of febrile infants ≤60 days old at 26 emergency departments in the Pediatric Emergency Care Applied Research Network. We evaluated the test characteristics of the urinalysis for diagnosing UTIs, with and without associated bacteremia, by using 2 definitions of UTI: growth of ≥50 000 or ≥10 000 colony-forming units (CFUs) per mL of a uropathogen. We defined a positive urinalysis by the presence of any leukocyte esterase, nitrite, or pyuria (>5 white blood cells per high-power field). RESULTS: Of 4147 infants analyzed, 289 (7.0%) had UTIs with colony counts ≥50 000 CFUs/mL, including 27 (9.3%) with bacteremia. For these UTIs, a positive urinalysis exhibited sensitivities of 0.94 (95% confidence interval [CI]: 0.91-0.97), regardless of bacteremia; 1.00 (95% CI: 0.87-1.00) with bacteremia; and 0.94 (95% CI: 0.90-0.96) without bacteremia. Specificity was 0.91 (95% CI: 0.90-0.91) in all groups. For UTIs with colony counts ≥10 000 CFUs/mL, the sensitivity of the urinalysis was 0.87 (95% CI: 0.83-0.90), and specificity was 0.91 (95% CI: 0.90-0.92). CONCLUSIONS: The urinalysis is highly sensitive and specific for diagnosing UTIs, especially with ≥50 000 CFUs/mL, in febrile infants ≤60 days old, and particularly for UTIs with associated bacteremia.