An Intact Cell Bioluminescence-Based Assay for the Simple and Rapid Diagnosis of Urinary Tract Infection.

Urinary tract infection (UTI) is one of the most common infections, accounting for a substantial portion of outpatient hospital and clinic visits. Standard diagnosis of UTI by culture and sensitivity can take at least 48 h, and improper diagnosis can lead to an increase in antibiotic resistance following therapy. To address these shortcomings, rapid bioluminescence assays were developed and evaluated for the detection of UTI using intact, viable cells of Photobacterium mandapamensis USTCMS 1132 or previously lyophilized cells of Photobacterium leiognathi ATCC 33981™. Two platform technologies-tube bioluminescence extinction technology urine (TuBETUr) and cellphone-based UTI bioluminescence extinction technology (CUBET)-were developed and standardized using artificial urine to detect four commonly isolated UTI pathogens-namely, Escherichia coli, Proteus mirabilis, Staphylococcus aureus, and Candida albicans. Besides detection, these assays could also provide information regarding pathogen concentration/level, helping guide treatment decisions. These technologies were able to detect microbes associated with UTI at less than 105 CFU/mL, which is usually the lower cut-off limit for a positive UTI diagnosis. Among the 29 positive UTI samples yielding 105-106 CFU/mL pathogen concentrations, a total of 29 urine specimens were correctly detected by TuBETUr as UTI-positive based on an 1119 s detection window. Similarly, the rapid CUBET method was able to discriminate UTIs from normal samples with high confidence (p ≤ 0.0001), using single-pot conditions and cell phone-based monitoring. These technologies could potentially address the need for point-of-care UTI detection while reducing the possibility of antibiotic resistance associated with misdiagnosed cases of urinary tract infections, especially in low-resource environments.

Clinical impact of rapid susceptibility testing on Mueller-Hinton Rapid-SIR directly from urine specimens.

Urinary tract infection diagnosis and management generally involves a 48-h microbiological delay to obtain the antibiotic susceptibility test (AST) results. In the context of multidrug resistance, reducing the time to obtain AST results is an essential factor, allowing for more timely appropriate treatment. We conducted a single-centre prospective study on urinary samples meeting two criteria: significant leukocyturia > 50/mm3 and exclusive presence of Gram-negative bacilli on direct examination. AST were performed by direct inoculation on Mueller-Hinton Rapid-SIR (MHR-SIR) agar. We evaluated the time to antibiotic adaptation by the antimicrobial stewardship team according to rapid AST results. Patients were subsequently excluded from the study if asymptomatic bacteria were confirmed, or in the absence of clinical data. Seventy patients were included. Mean age of patients was 68.8 years (± 21.3). Empirical antibiotic treatment were mainly based on third generation cephalosporins (n = 33), fluoroquinolones (n = 15), beta-lactamin/beta-lactamase inhibitors (n = 7), fosfomycin and nitrofurantoin (n = 5, each). The average time to obtain results was 7.2 h (± 1.6 h). Adaptation of therapy following MHR-SIR was performed for 29 patients (41%) with early switch to oral antibiotics, de-escalation or escalation in respectively 72.3%, 30%, and 11% of cases. Time saving of MHR-SIR compared with the standard technique was 42.6 (± 16.7) h. This study showed that rapid antibiotic susceptibility test results, using MHR-SIR method directly from urine, can be obtained 40 h earlier than conventional AST. The study also demonstrated significant clinical impact on the selection and reduction of the antibiotic therapy spectrum.

A Diaper Pad for Diaper-Based Urine Collection and Colorimetric Screening of Urinary Biomarkers.

The high prevalence of urinary tract infection in aging adults is a challenging aspect of geriatric care. Incontinence and cognitive/functional impairment make collection of urine samples difficult and often require either catheterization for sample collection, which is a risk factor for infections, or more lenient criteria for initiating antibiotic treatment. We report the development of a diaper inlay with absorbent materials, superabsorbent polymer-based valve and chemical reaction pads for rapid screening of urinary tract infection of incontinent diaper-wearing elderly receivers of home care services. The developed diaper inlay was capable of collecting, isolating, analyzing samples and retaining results > 8 h. The diaper inlay can therefore be compatible with the diaper changing routines of nurses in home care services, without requiring much time or effort. A nurse can insert a diaper inlay in a diaper and the results can be recorded during a later diaper change. Although the research focuses on tools for home care services, the nursing home sector has similar problems and may benefit from technological development for rapid screening to avoid unnecessary catheterization and overuse of antibiotics.

Metabolic risk factors in pediatric stone formers: a report from an emerging economy.

The goal of this study was to investigate metabolic risk factors in pediatric stone formers in an emerging economy. A prospective, data collection enrolled 250 children age <1-15 years at our center. Risk factors were evaluated by gender and in age groups <1-5, 6-10 and 11-15 years. Patients were evaluated for demographics, blood and 24 h urine for calcium, magnesium, phosphate, uric acid, electrolytes and additional protein, citrate, ammonia and oxalate in urine. All reported values were two sided and statistical significance was considered at p value ≤0.05. The mean age at diagnosis was 7.50 ± 3.56 years with a male to female ratio of 1.84:1. A family history of urolithiasis was found in 41 (16.4 %), urinary tract infection in 18 (7 %) and chronic diarrhea in 75 (30 %). Hypercalcemia was seen in 37 (14.8 %), hyperuricemia in 23 (9.2 %) and hyperphosphatemia in 6 (2.4 %). Urinary metabolic abnormalities were identified in 248 (98 %) of the cases. Hypocitraturia was found in 207 (82.8 %), hyperoxaluria in 62 (26.4 %), hyperuricosuria in 82 (32.8 %), hypercalciuria in 51 (20.4 %), hyperphosphaturia in 46 (18.4 %), hyperammonuria in 10 (4 %), hypocalciuria in 82 (32.8 %), and hypovolemia in 73 (29.2 %). Risk factors were similar between genders except higher rates of hyponatriuria, hypophosphaturia, and hypocalciuria in females. Hyperuricosuria, hyponatriuria, and hypovolemia were highest in 1-5 years (52, 49, 49 %) as compared to (18, 21, 12 %) those in 11-15 years (p < 0.001), respectively. This study shows that careful metabolic analysis can identify risk factors in 98 % of the children where appropriate metaphylaxis can be undertaken both for treatment and prevention of recurrence.

Incidence and Management of Uncomplicated Recurrent Urinary Tract Infections in a National Sample of Women in the United States.

OBJECTIVE: To determine the incidence and characteristics of women with uncomplicated recurrent urinary tract infections (UTIs) and to explore whether the use of culture-driven treatment affects rates of UTI-related complications and resource utilization. MATERIALS AND METHODS: Using MarketScan claims from 2003 to 2011, we identified UTI-naive women ages 18-64 with incident-uncomplicated recurrent UTIs. Recurrent UTIs were defined as 3 UTI visits associated with antibiotics during a 12-month period. Cases were excluded if they had a UTI in the preceding year, or if they had any complicating factors (eg, abnormality of the urinary tract, neurologic condition, pregnancy, diabetes, or currently taking immunosuppression). We next assessed use of urine cultures, imaging, and cystoscopy, and performed propensity score matching with logistic regression to determine whether having a urine culture associated with >50% of UTIs affected rates of complications and downstream resource utilization. RESULTS: We identified 48,283 women with incident-uncomplicated recurrent UTIs, accounting for an overall incidence of 102 per 100,000 women, highest among women ages 18-34 and 55-64. Sixty-one percent of these women had at least 1 urine culture, 6.9% had imaging, and 2.8% had cystoscopy. Having a urine culture >50% of the time was associated with fewer UTI-related hospitalizations and lower rates of intravenous antibiotic use, whereas demonstrating higher rates of UTI-related office visits and pyelonephritis. CONCLUSION: The incidence of uncomplicated recurrent UTIs increases with age. Urine culture-directed care is beneficial in reducing high-cost services including UTI-related hospitalizations and intravenous antibiotic use, making urine cultures a valuable component to management of these patients.

Variable selection in covariate dependent random partition models: an application to urinary tract infection.

Lower urinary tract symptoms can indicate the presence of urinary tract infection (UTI), a condition that if it becomes chronic requires expensive and time consuming care as well as leading to reduced quality of life. Detecting the presence and gravity of an infection from the earliest symptoms is then highly valuable. Typically, white blood cell (WBC) count measured in a sample of urine is used to assess UTI. We consider clinical data from 1341 patients in their first visit in which UTI (i.e. WBC ≥ 1) is diagnosed. In addition, for each patient, a clinical profile of 34 symptoms was recorded. In this paper, we propose a Bayesian nonparametric regression model based on the Dirichlet process prior aimed at providing the clinicians with a meaningful clustering of the patients based on both the WBC (response variable) and possible patterns within the symptoms profiles (covariates). This is achieved by assuming a probability model for the symptoms as well as for the response variable. To identify the symptoms most associated to UTI, we specify a spike and slab base measure for the regression coefficients: this induces dependence of symptoms selection on cluster assignment. Posterior inference is performed through Markov Chain Monte Carlo methods.

Careful assessment key in managing prostatitis.

Prostatitis is a common condition estimated to affect up to 30% of men in their lifetime, it is most prevalent in men aged between 35 and 50. Prostatitis is subclassified into: acute bacterial prostatitis, chronic bacterial prostatitis, chronic pelvic pain and asymptomatic inflammatory prostatitis. Acute bacterial prostatitis presents with acute onset pelvic pain which may or may not be related to voiding, lower urinary tract symptoms, sometimes haematuria or haematospermia and systemic symptoms such as fever and rigors. A documented history of recurrent urinary tract infections is the key feature of chronic bacterial prostatitis. Duration of symptoms > 3 months defines chronicity. The key symptom of chronic pelvic pain syndrome is pain. Patients may describe pain during or after ejaculation as their predominant symptom. Clinical assessment includes a thorough history and examination. A digital rectal examination should be performed after a midstream urine (MSU) sample has been collected for urine dipstick, microscopy and culture. The prostate should be checked for nodules. In acute bacterial prostatitis the MSU is the only laboratory investigation required. Chronic pelvic pain syndrome may be multifactorial and part of a more generalised pain disorder. Pelvic floor muscle abnormalities, altered neuroendocrine pathways, chemically induced inflammation, bacterial infection, autoimmune processes, dysfunctional voiding as well intraprostatic ductal reflux mechanisms have all been identified in men with chronic pelvic pain syndrome.

Incidence, severity, help seeking, and management of uncomplicated urinary tract infection: a population-based survey.

BACKGROUND: Limited knowledge of the population incidence and management of uncomplicated urinary tract infection (UTI) limits information provision and interventions to enhance care in the community. AIM: To describe incidence and severity, help seeking, and management of UTI from a population perspective. DESIGN AND SETTING: Household survey in England in 2014. METHOD: In total, a random sample of 2424 females aged ≥16 years were interviewed in their own homes using computer-assisted interviewing about their UTI symptoms, help seeking, and management. Data were weighted by sex, age, ethnicity, working status, social grade, and housing tenure, and Government Office Region to be broadly representative of the general population. RESULTS: Of the females interviewed, 892 (37%) reported having had at least one UTI in their lifetime (29% had more than one episode). In the past year, 11% of all females reported a UTI and 3% recurrent UTI (≥3 or more). Of those who had ever had a UTI, 48% rated their last UTI as fairly or very severe. In total, 95% consulted a health professional; 65% at their local GP practice during routine consulting hours. Out-of-hours consulting was uncommon but more prevalent in younger females. Of those contacting a health professional, 76% had a urine test, 74% were prescribed an antibiotic, but only 63% of these reported taking the antibiotic. Delayed antibiotic prescribing was rare. CONCLUSION: UTI symptoms are common; most females consult in general practice, and are prescribed antibiotics, but one-third report not taking the antibiotics as prescribed. Benefit and harms in those taking, and not taking, antibiotics need to be better understood in order to improve help seeking, management, and adherence. Urine tests and antibiotics could be reduced by basing empirical antibiotics on symptoms, and increasing use of back-up prescriptions.

Human urine is not sterile - shift of paradigm.

OBJECTIVE: Until recently the generally accepted paradigm implied that urine of healthy people is sterile. In the present study, urine of healthy subjects was investigated by extended bacteriological methods. MATERIAL AND METHODS: Three midstream urine samples from 52 healthy subjects each (24 females, 28 males; 18-25 years of age) were investigated by an extended set of culture media for identification of facultative aerobic (FAB) and nonclostridial anaerobic bacteria (NCAB). Ward's method (Euclidean distance) was used for similarity analysis. RESULTS: The bacterial count of FAB in urine was usually low (≤ 10(2) colony-forming units/ml) in both groups. In contrast, the bacterial count of NCAB was higher (≥ 10(3) colony-forming units/ml), at least in some species, with significant differences between genders. The average number of bacterial species found was 5.8 in female and 7.1 in male urine. Half of the females were assigned to a specific 'female' microbial spectrum, different from that of males. In the mixed-gender clusters, the males showed a greater similarity among themselves. CONCLUSIONS: As also shown by other investigators, urine of healthy people is normally not sterile. The role of the routinely not cultivated bacteria in healthy and diseased subjects needs to be established. It may alter the diagnostics of infectious and inflammatory diseases of the urogenital tract.

Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for urinary tract infection: assessment of protective effects in a rat model.

OBJECTIVE: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. METHODS: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. RESULTS: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 × 10(3) cfu/mL) and chondroitin sulfate (1 × 10(4) cfu/mL) groups relative to the control group (5 × 10(4) cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 × 10(2) cfu/mL; P < 0.05). In the bladder tissues, statistically significant decreases in median bacterial growth rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium damage decreased in the treatment groups. However, this effect was prominent in hyaluronic acid + chondroitin sulfate group. CONCLUSION: Our experimental findings show that the hyaluronic acid + chondroitin sulfate combination has a potential benefit in reducing the bacterial load in urine and the thickness of the transitional epithelium.

Evaluación de sensibilidad antibiótica en urocultivos de pacientes en primer nivel de atención en salud de Pereira / Using an antibiotic sensitivity assay on urine cultures from patients attending general practice healthcare institutions in Pereira

Objetivos: Las Infecciones de vías urinarias son una causa de consulta muy frecuente en primer nivel de atención en salud. Describir los gérmenes más frecuentemente aislados y los patrones de resistencia a los antibióticos en urocultivos y antibiogramas de pacientes de primer nivel de atención de Pereira. Materiales y Métodos: Estudio descriptivo observacional de corte transversal, en una población de 131 608 afiliados al Sistema General de Seguridad Social en Salud entre el 1 de enero de 2010 y 7 de abril de 2011 evaluando las bacterias aisladas en urocultivos procesados con más de 100 000 Unidades Formadoras de Colonias y resultados de sensibilidad y resistencia de antibiogramas. La resistencia se evaluó bajo parametros de Clinical and Laboratory Standards Institute mediante método manual de difusión de disco Kirby-Bauer con sensidiscos Beckton Dickinson Diagnostics. Resultados: Se realizaron 5 226 urocultivos, de los cuales 1 058 mostraron crecimiento de uropatógenos. Un total de 792 (74,9 %) cultivos reportó el crecimiento de más de 105 UFC, Los microorganismos más frecuentemente aislados fueronEscherichia coli(67,2 %),Klebsiella sp(19,2 %) yEnterococcus sp(7,8 %).Escherichia colimostró sensibilidad alta para amoxicilina/clavulanato (100 %), nitrofurantoina (94,8 %), ceftriaxona (86,3 %), ciprofloxacina (71,0 %) y resistencia elevada para ampicilina (54,7 %), amoxicilina (50,0 %), trimetoprimsulfametoxazole (43,8 %) y cefalotina (42,8 %). Conclusiones: Nitrofurantoina puede ser la mejor opción terapéutica en primera línea de manejo en infecciones de vías urinarias bajas y ciprofloxacina para pielonefritis debido a su efectividad y poca resistencia en primer nivel de atención en Pereira.

Objectives: Describing the bacteria most frequently isolated from and antibiotic resistance patterns in urine cultures taken from patients attending general practice healthcare institutions in Pereira as urinary tract infections are a frequent cause for primary healthcare attention. Materials and Methods: A descriptive cross-sectional observational study of 131,608 members of the health social security system was carried out between January 1st 2010 and April 7th 2011;the bacteria isolated from urine cultures having more than 105 colony-forming units (CFU) were assessed, as were the sensitivity and antibacterial agents’ resistance results. Resistance was evaluated in line with Clinical and Laboratory Standards Institute (CLSI) parameters by means of the Kirby-Bauer disk diffusion manual method with Beckton Dickinson diagnostic disks. Results: 5,226 urine cultures were analysed, 1,058 of which showed uropathogengrowth. Bacterial growth was reported in 792 cultures (74.9 %), having more than 105 CFU. The most frequently isolated microorganisms were Escherichia coli (67.2 %), Klebsiella sp (19.2 %) and Enterococcus sp (7.8 %).Escherichia colishowed high sensitivity to amoxicillin / clavulanate (100 %), nitrofurantoin (94.8 %), ceftriaxone (86.3 %), ciprofloxacin (71.0 %) and high resistance to ampicillin (54.7 %), amoxicillin (50.0 %), trimethoprim-sulfamethoxazole (43.8 %) and cephalothin (42.8 %). Conclusions: Nitrofurantoin may be the best therapeutic option in first-line management of lower urinary tract infection and ciprofloxacin for pyelonephritis due to its effectiveness and low resistance as seen in primary healthcare practice in Pereira.

[Using an antibiotic sensitivity assay on urine cultures from patients attending general practice healthcare institutions in Pereira]. / Evaluación de sensibilidad antibiótica en urocultivos de pacientes en primer nivel de atención en salud de Pereira.

OBJECTIVES: Describing the bacteria most frequently isolated from and antibiotic resistance patterns in urine cultures taken from patients attending general practice healthcare institutions in Pereira as urinary tract infections are a frequent cause for primary healthcare attention. MATERIALS AND METHODS: A descriptive cross-sectional observational study of 131,608 members of the health social security system was carried out between January 1st 2010 and April 7th 2011;the bacteria isolated from urine cultures having more than 105 colony-forming units (CFU) were assessed, as were the sensitivity and antibacterial agents' resistance results. Resistance was evaluated in line with Clinical and Laboratory Standards Institute (CLSI) parameters by means of the Kirby-Bauer disk diffusion manual method with Beckton Dickinson diagnostic disks. RESULTS: 5,226 urine cultures were analysed, 1,058 of which showed uropathogengrowth. Bacterial growth was reported in 792 cultures (74.9 %), having more than 105 CFU. The most frequently isolated microorganisms were Escherichia coli (67.2 %), Klebsiella sp (19.2 %) and Enterococcus sp (7.8 %).Escherichia colishowed high sensitivity to amoxicillin / clavulanate (100 %), nitrofurantoin (94.8 %), ceftriaxone (86.3 %), ciprofloxacin (71.0 %) and high resistance to ampicillin (54.7 %), amoxicillin (50.0 %), trimethoprim-sulfamethoxazole (43.8 %) and cephalothin (42.8 %). CONCLUSIONS: Nitrofurantoin may be the best therapeutic option in first-line management of lower urinary tract infection and ciprofloxacin for pyelonephritis due to its effectiveness and low resistance as seen in primary healthcare practice in Pereira.

[Evaluation of chromogenic medium Uriselect4 in urine culture]. / Évaluation du milieu chromogène Uriselect4 au cours des urocultures.

We evaluated the performance and the cost of chromogenic medium Uriselect4 agar with regard to the standard medium for the detection and identification of urinary tract pathogens. A total of 503 clinical urine specimens containing leucocytes greater or equal to 104/mL were analysed prospectively, in parallel by two different persons on blood agar (GS) and Uriselect4 according to the manufacturers' instructions. Of the 503 urine specimens tested, 210 gave a positive culture on Uriselect4 versus 181 on GS. The majority of bacterial species grew on both media; enterobacteria grew on Uriselect4 better than GS. The identification of Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), KES group and Enterococcus faecalis (E. faecalis) did not require the use of galleries Api and has a gain of 24  h. Positive pure cultures on Uriselect4 corresponding to negative cultures of GS were noted in 17 ases. Conversely, in seven cases a positive pure culture on GS was noted while the corresponding Uriselect4 cultures were negative. The cost of identification on GS (including the cost of galleries Api), was about two times higher than Uriselect4. Uriselect4 medium isolates the most frequent urinary tract pathogens and identify them so almost immediately, with a lower cost.

Adolescent female with urinary symptoms: a diagnostic challenge for the pediatrician.

OBJECTIVES: The objective of this study was to determine the accuracy with which physicians diagnose sexually transmitted infections (STIs) and urinary tract infections (UTIs) in adolescent females with urinary symptoms. Secondary aims were to determine the prevalence of STIs and UTIs in this subset of patients and to identify variables associated with a physician diagnosis of STI or UTI. METHODS: We performed a prospective cross-sectional study of females aged 13 to 21 years who presented to an urban pediatric emergency department with urinary symptoms. Pediatric emergency medicine physicians' diagnoses of STI or UTI were compared with the criterion standard of diagnosis. RESULTS: Of the 233 patients enrolled, 211 had complete data sets and were included for analysis. Nineteen patients (9%) had STIs. Physicians predicted STIs in 35 patients (17%), of which 9 (25%) had true infections. Sexually transmitted infections in 10 patients (53%) were underdiagnosed, in 26 patients (74%) were overdiagnosed, and in 9 patients (26%) were correctly diagnosed. One hundred twenty patients (57%) had UTIs. Physicians predicted UTIs in 156 patients (74%), of which 107 (69%) had culture-confirmed UTIs. Urinary tract infections in 13 patients (11%) were underdiagnosed, in 49 patients (31%) were overdiagnosed, and in 107 patients (66%) were correctly diagnosed. Thirteen patients (6%) had a coinfection with both an STI and a UTI. CONCLUSIONS: Pediatric emergency medicine physicians both underdiagnose and overdiagnose STIs and UTIs in patients with urinary symptoms. This diagnostic challenge necessitates that all adolescent patients presenting with urinary symptoms should be tested for STIs and UTIs and have adequate follow-up means established to ensure timely treatment.

[Comparison of two protocols of febrile urinary tract infection management in children]. / Comparaison de deux protocoles de prise en charge des infections urinaires fébriles de l'enfant.

PURPOSE: To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost. METHODS: This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts. RESULTS: A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (€2235 in 2005, €2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (€1292 versus €1882 in 2005; P=0.0042). CONCLUSION: Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.

Assessment of urine solute and matrix effects on the performance of an enzyme-linked immunosorbent assay for measurement of interleukin-6 in dog urine.

Measurement of cytokine concentrations within body fluids is a means of recognizing subclinical and/or unresolved, infectious and inflammatory states in patients. In the urinary tract, such information may be useful for identifying patients with pyelonephritis, asymptomatic bacteriuria, recurrent infections, and cystitis. One such cytokine, interleukin-6 (IL-6), is recognized as a primary cytokine that is produced following exposure of the urothelium to bacterial virulence factors. Complicating reliable testing for this and other cytokines is the nature of urine itself. Urine varies widely in its composition as indicated by the range of pH and urine specific gravity (USG) observed in healthy patients. An additional variable is the protein and carbohydrate matrix capable of hindering immunologic testing modalities, such as enzyme-linked immunosorbent assays (ELISAs). The purpose of the current study was to examine the role of urine pH, USG, and matrix while optimizing a canine-specific chemiluminescent ELISA for the measurement of IL-6 in the urine of dogs. Urine spiked with IL-6 obtained maximal IL-6 quantitative recoveries of only 55 ± 10% (mean ± 1 standard deviation) when an ELISA optimized for cell culture supernatants was used. The urine matrix and variations in USG were determined to by contributing to this poor IL-6 recovery. Using specific matrix inhibitors and optimal dilutions improved the IL-6 quantitative recovery to 91 ± 5%. Urine pH (5.5-9.5) had no effect. The current work underscores the importance of critically optimizing testing modalities for biomarkers, particularly if they are immunologic in origin.

Irrigation of continent catheterizable ileal pouches: tap water can replace sterile solutions because it is safe, easy, and economical.

BACKGROUND: Continent catheterizable ileal pouches require regular irrigations to reduce the risk of bacteriuria and urinary tract infections (UTIs). OBJECTIVE: Our aim was to compare the UTI rate, patient friendliness, and costs of standard sterile irrigation versus irrigation with tap water. DESIGN, SETTING, AND PARTICIPANTS: Twenty-three patients participated in a prospective randomized two-arm crossover single-center trial. Aseptic intermittent self-catheterization (ISC) combined with sterile sodium chloride (NaCl) 0.9% irrigation was compared with clean ISC and irrigation with tap water (H(2)O) during two study periods of 90 d each. INTERVENTION: Patients underwent daily pouch irrigations with NaCl 0.9% solution or tap water. MEASUREMENTS: Urine nitrite dipstick tests were evaluated daily; urine culture (UC) and patient friendliness were evaluated monthly. Costs were documented. RESULTS AND LIMITATIONS: A total of 3916 study days with nitrite testing and irrigation were analyzed, 1876 (48%) in the NaCl arm and 2040 (52%) in the H(2)O arm. In the NaCl arm, 418 study days (22%) with nitrite-positive dipsticks were recorded, 219 d (11%) in the H(2)O arm, significantly fewer (p=0.01). Of the 149 UCs, 96 (64%) were positive, 48 in each arm, revealing a total of 16 different germs. All patients preferred the H(2)O method. Monthly costs were up to 20 times lower in the H(2)O arm. CONCLUSIONS: Pouch irrigation with sterile NaCl 0.9% solution and tap water had comparable rates of positive UC. Irrigation with tap water significantly lowered the incidence of nitrite-positive study days and was substantially less costly and more patient friendly than NaCl irrigation. We therefore recommend the use of tap water (or bottled water) instead of sterile NaCl 0.9% solution for daily irrigation of continent catheterizable ileal pouches. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12610000618055, http://www.ANZCTR.org.au/ACTRN12610000618055.aspx.

Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

OBJECTIVES: To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management. DESIGN: There were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT. SETTING: Primary care. PARTICIPANTS: Women aged 17-70 with suspected UTI. INTERVENTIONS: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU). MAIN OUTCOME MEASURES: Antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms. RESULTS: (1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear. CONCLUSIONS: To achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.

Comparison of sampling methods for urine cultures.

PURPOSE: To compare efficacy and cost of conventional and alternative sampling methods concerning urine cultures. DESIGN AND METHODS: An experimental study with two replications was carried out in a 900-bed university hospital in Ankara, Turkey. The sample was 160 hospitalized female patients, who were asked to give urine specimens, September 10,2000 and September 1,2001. They were patients on urology and obstetrics and gynaecology wards. The authors informed the patients about the study first and then obtained two samples from each patient under their observation. The number of specimens was 320. Statistical methods were descriptive. FINDINGS: The rates of contamination and significant growth, respectively, were 4.4% and 7.5% for the conventional method and 5.6% and 10% for the alternative method. The cost per culture was 2.588.257 TL (2.10 USD) for the conventional method and 57.021 TL (0.05 USD) for the alternative method. The cost difference was statistically significant. CONCLUSIONS: The two methods yielded similar results but the alternative method was less expensive.