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1.  Validating the prediction of lower urinary tract infection in primary care: sensitivity and specificity of urinary dipsticks and clinical scores in women 
Background
Dipsticks are one of the most commonly used near-patient tests in primary care, but few clinical or dipstick algorithms have been rigorously developed.
Aim
To confirm whether previously documented clinical and dipstick variables and algorithms predict laboratory diagnosis of urinary tract infection (UTI).
Design of study
Validation study.
Setting
Primary care.
Method
A total of 434 adult females with suspected lower UTI had bacteriuria assessed using the European Urinalysis Guidelines.
Results
Sixty-six per cent of patients had confirmed UTI. The predictive values of nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) were confirmed (independent multivariate odds ratios = 5.6, 3.5, and 2.1 respectively). The previously developed dipstick rule — based on presence of nitrite, or both leucocytes and blood — was moderately sensitive (75%) but less specific (66%; positive predictive value [PPV] 81%, negative predictive value [NPV] 57%). Predictive values were improved by varying the cut-off point: NPV was 76% for all three dipstick results being negative; the PPV was 92% for having nitrite and either blood or leucocyte esterase. Urine offensive smell was not found to be predictive in this sample; for a clinical score using the remaining three predictive clinical features (urine cloudiness, dysuria, and nocturia), NPV was 67% for none of the features, and PPV was 82% for three features.
Conclusion
A clinical score is of limited value in increasing diagnostic precision. Dipstick results can modestly improve diagnostic precision but poorly rule out infection. Clinicians need strategies to take account of poor NPVs.
doi:10.3399/bjgp10X514747
PMCID: PMC2894378  PMID: 20594439
algorithms, clinical scoring; diagnosis, urinary tract infection; primary care; urinalysis
2.  Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores 
Background
Suspected urinary tract infection (UTI) is one of the most common presentations in primary care. Systematic reviews have not documented any adequately powered studies in primary care that assess independent predictors of laboratory diagnosis.
Aim
To estimate independent clinical and dipstick predictors of infection and to develop clinical decision rules.
Design of study
Validation study of clinical and dipstick findings compared with laboratory testing.
Setting
General practices in the south of England.
Method
Laboratory diagnosis of 427 women with suspected UTI was assessed using European urinalysis guidelines. Independent clinical and dipstick predictors of diagnosis were estimated.
Results
UTI was confirmed in 62.5% of women with suspected UTI. Only nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) independently predicted diagnosis (adjusted odds ratios 6.36, 4.52, 2.23 respectively). A dipstick decision rule, based on having nitrite, or both leucocytes and blood, was moderately sensitive (77%) and specific (70%); positive predictive value (PPV) was 81% and negative predictive value (NPV) was 65%. Predictive values were improved by varying the cut-off point: NPV was 73% for all three dipstick results being negative, and PPV was 92% for having nitrite and either blood or leucocyte esterase. A clinical decision rule, based on having two of the following: urine cloudiness, offensive smell, and dysuria and/or nocturia of moderate severity, was less sensitive (65%) (specificity 69%; PPV 77%, NPV 54%). NPV was 71% for none of the four clinical features, and the PPV was 84% for three or more features.
Conclusions
Simple decision rules could improve targeting of investigation and treatment. Strategies to use such rules need to take into account limited negative predictive value, which is lower than expected from previous research.
PMCID: PMC1874525  PMID: 16882379
clinical scoring algorithms; diagnosis, urinary tract infection; dipsticks
3.  Diagnostic accuracy of rapid urine dipstick test to predict urinary tract infection among pregnant women in Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia 
BMC Research Notes  2014;7:481.
Background
Untreated bacteriuria during pregnancy has been shown to be associated with low birth-weight and premature delivery. Therefore, routine screening for bacteriuria is advocated. The decision about how to screen pregnant women for bacteriuria has always been a balance between the cost of screening versus the sensitivity and specificity. This study was designed to evaluate the diagnostic accuracy of the rapid dipstick test to predict urinary tract infection in pregnancy against the gold standard urine culture.
Method
A total of 367 mid stream urine samples were collected, inoculated on MacConkey, Manitol salt agar (MSA) and blood agar and incubated aerobically at 37°C for overnight. Specimens were classified as “positive” for urinary tract infection (UTI) if the growth of the pathogen(s) was at a count ≥ 105 colony-forming units per milliliter (cfu/mL) of urine and classified as “negative” with growth of <105 cfu/mL. Urine samples were tested for the presence of nitrite and leukocyte esterase using dipstick rapid test in accordance to the manufacturer’s instructions.
Results
From the total study participants, 37 pregnant women were symptomatic and the remaining 330 pregnant women were asymptomatic. The sensitivity and specificity of dipstick tests of leukocyte esterase was 50% and 89.1% for pregnant women with asymptomatic UTI(ABU) and 71.4% and 86.7% for symptomatic UTI respectively and for nitrite 35.7% and 98.0% for ABU and 57.1% and 96.7% symptomatic UTI.
Conclusion
This study revealed that the use of dipstick leukocyte esterase and nitrite for screening UTI particularly asymptomatic bacteriuria was associated with many false positive and negative results when it was compared against the gold standard culture method. The low sensitivity and positive predictive value of urine dipstick test proved that culture should be used for the diagnosis of UTI.
doi:10.1186/1756-0500-7-481
PMCID: PMC4118157  PMID: 25073620
Dipstick test; Pregnant women; UTI; Asymptomatic bacteriuria
4.  Disappointing dipstick screening for urinary tract infection in hospital inpatients. 
Journal of Clinical Pathology  1998;51(6):471-472.
AIM: To compare the performance of leucocyte esterase and nitrite dipstick tests with microscopic examination and culture of first morning urines (n = 420) of hospital inpatients. RESULTS: The sensitivity, specificity, and negative predictive value of the leucocyte esterase test for the cutoff of > 10 WBC/microliter were 57%, 94%, and 68%, respectively. For > 5 WBC per high power field (HPF) these variables were 84%, 90%, and 93%. For > 10(5) colony counts/ml, the sensitivity of the nitrite test was 27%, specificity 94%, and negative predictive value 87%. When either leucocyte esterase or nitrite positivity was accepted as a marker of urinary tract infection, the sensitivity was 78%, specificity 75%, and negative predictive value 94%, and there were 22% false negative results. Semiquantitative microscopic estimation of bacteria per HPF yielded 40% false positives. CONCLUSIONS: Leucocyte esterase and nitrite dipstick tests are not suitable for screening for urinary tract infections.
PMCID: PMC500752  PMID: 9771448
5.  Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial 
Objective To assess the impact of different management strategies in urinary tract infections.
Design Randomised controlled trial.
Setting Primary care.
Participants 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection.
Intervention Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group.
Main outcome measures Symptom severity (days 2 to 4) and duration, and use of antibiotics.
Results Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57 (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for 37% longer than those taking immediate antibiotics (incident rate ratio 1.37 (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22% to 140%; none of the other groups had more than 22% longer duration).
Conclusion All management strategies achieve similar symptom control. There is no advantage in routinely sending midstream urine samples for testing, and antibiotics targeted with dipstick tests with a delayed prescription as backup, or empirical delayed prescription, can help to reduce antibiotic use.
Study registration National Research Register N0484094184 ISRCTN: 03525333.
doi:10.1136/bmj.c199
PMCID: PMC2817051  PMID: 20139214
6.  The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy 
BMC Urology  2004;4:4.
Background
Many studies have evaluated the accuracy of dipstick tests as rapid detectors of bacteriuria and urinary tract infections (UTI). The lack of an adequate explanation for the heterogeneity of the dipstick accuracy stimulates an ongoing debate. The objective of the present meta-analysis was to summarise the available evidence on the diagnostic accuracy of the urine dipstick test, taking into account various pre-defined potential sources of heterogeneity.
Methods
Literature from 1990 through 1999 was searched in Medline and Embase, and by reference tracking. Selected publications should be concerned with the diagnosis of bacteriuria or urinary tract infections, investigate the use of dipstick tests for nitrites and/or leukocyte esterase, and present empirical data. A checklist was used to assess methodological quality.
Results
70 publications were included. Accuracy of nitrites was high in pregnant women (Diagnostic Odds Ratio = 165) and elderly people (DOR = 108). Positive predictive values were ≥80% in elderly and in family medicine. Accuracy of leukocyte-esterase was high in studies in urology patients (DOR = 276). Sensitivities were highest in family medicine (86%). Negative predictive values were high in both tests in all patient groups and settings, except for in family medicine. The combination of both test results showed an important increase in sensitivity. Accuracy was high in studies in urology patients (DOR = 52), in children (DOR = 46), and if clinical information was present (DOR = 28). Sensitivity was highest in studies carried out in family medicine (90%). Predictive values of combinations of positive test results were low in all other situations.
Conclusions
Overall, this review demonstrates that the urine dipstick test alone seems to be useful in all populations to exclude the presence of infection if the results of both nitrites and leukocyte-esterase are negative. Sensitivities of the combination of both tests vary between 68 and 88% in different patient groups, but positive test results have to be confirmed. Although the combination of positive test results is very sensitive in family practice, the usefulness of the dipstick test alone to rule in infection remains doubtful, even with high pre-test probabilities.
doi:10.1186/1471-2490-4-4
PMCID: PMC434513  PMID: 15175113
7.  A urine analysis method suitable for children's nappies. 
Journal of Clinical Pathology  1997;50(7):569-572.
BACKGROUND: Urinary tract infection in infancy continues to be underdiagnosed, despite its association with renal scarring and thus hypertension, renal failure, and other sequelae. Low ascertainment of urinary tract infections reflects the many difficulties in establishing a diagnosis, some of which could be eliminated by a simple, reliable method for preliminary investigation of children's urine. AIM: To assess the accuracy of a new, simple method for testing urine for nitrite and leucocyte esterase, which could be applied to children in primary care. METHODS: An in vitro study was carried out to compare the results of conventional urine analysis with urine analysis on urine soaked on to panty-liners, and with the laboratory investigation. Two urine analysis stick types were used (Boehringer Mannheim Nephur sticks and Bayer Multistix 8SG) and two brands of panty-liners. Analysis examined evidence of agreement and bias for different methods in addition to sensitivity, specificity, and negative predictive values for urine analysis. RESULTS: Pressing urine analysis test sticks on to panty-liners soaked with urine achieved consistent results compared with the results of conventional dipstick urine analysis. At a prevalence of 21.8%, sensitivity and negative predictive values of urine analysis for laboratory confirmed urinary tract infection were 94% and 98%, respectively, for Boehringer sticks, and 76% and 93%, respectively, for Bayer sticks. At prevalences of 5% and 1% (prevalences that could be expected in primary care) Bayer sticks had negative predictive values of 98.7% and 99.7%, respectively, and Boehringer sticks had values of 99.6% and 99.9%, respectively. CONCLUSIONS: Testing urine on panty-liners is accurate compared with conventional urine analysis. It may be possible to apply this method to testing unwell children presenting in primary care to identify those who require microbiological urine culture to confirm or eliminate a diagnosis of urinary tract infection.
PMCID: PMC500054  PMID: 9306937
8.  Evaluation of a screening test for detecting urinary tract infection in newborns and infants. 
Journal of Clinical Pathology  1991;44(12):1029-1030.
The results of a study of a screening test for urinary tract infection (UTI) in infants under 18 months is reported. Two hundred and forty three urine specimens were tested in the laboratory using AMES Multistix 8SG reagent strips read by photometer. The strips included three potential markers for urinary tract infection: leucocyte esterase, nitrite, and protein. The predictive value of a positive result (PPV) was low. The predictive value of negative test (NPV) when combining the screen of leucocyte esterase, nitrite, and protein was 99.4% with no difference between boys and girls. The test for leucocyte esterase had a 97.6% negative predictive value. An examination of the results by age confirms the good NPV in all age groups. Paediatricians should find Multistix 8SG strips a useful aid in the diagnosis of urinary tract infection in infants, and that costly culture of samples with negative strip tests can be avoided.
PMCID: PMC494975  PMID: 1791205
9.  Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection 
PLoS Medicine  2007;4(12):e329.
Background
Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI.
Methods and Findings
We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria.
Conclusions
The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.
Analyzing urine specimens from women with bladder infections, Scott Hultgren and colleagues find evidence for intracellular bacterial communities, which have been associated with recurrent urinary tract infections in mice.
Editors' Summary
Background.
Every year, nearly 10 million people in the United States—mainly women—consult their doctors because of a urinary tract infection (UTI). UTIs occur when bacteria living in the gut—usually Escherichia coli—get transferred to the opening of the urethra (the tube through which urine leaves the body), as may occur during sexual intercourse. From here, the bacteria can move into the bladder (the muscular sac that stores urine until it is excreted) where they can multiply and cause cystitis (inflammation of the bladder). If cystitis is untreated, the bacteria can move further up the urinary tract and infect the kidneys (which make urine). Symptoms of UTIs include pain when urinating, frequent and intense urges to urinate, and cloudy urine. UTIs are diagnosed by looking for bacteria and white blood cells (that fight infection) in the urine; the usual treatment is a short course of antibiotics.
Why Was This Study Done?
Half the women who get a UTI will have another attack within a year, often caused by the same bacterial strain. It is generally thought that these strains persist in the gut and reinfect the urinary tract, but recent animal studies suggest an additional explanation. In mice, E. coli strains that cause UTIs can invade the cells lining the bladder. Here, they replicate and form so-called intracellular bacterial communities (IBCs). Many of the infected cells fall off the bladder's surface into the urine, but IBCs also release bacteria, many of which have a long, slender filamentous appearance (E. coli usually have a simple rod-like shape). Immune system cells normally kill bacteria in the urine but cannot deal with filamentous bacteria. In mice, these bacteria can then reinfect the lining of the bladder and establish long-lasting intracellular reservoirs of bacteria that are protected from antibiotics and probably from the host immune system. If this IBC cycle occurs in people, it might explain why some UTIs recur and might suggest ways to manage these recurrences. In this study, therefore, the researchers have investigated whether there is an IBC cycle in women.
What Did the Researchers Do and Find?
The researchers collected urine from 80 young women with cystitis and from 20 women with no symptoms who had had cystitis previously. They identified the type of bacteria in each sample and looked for IBCs and filamentous bacteria using light microscopy, electron microscopy, and a technique called immunofluorescence. None of the women without cystitis had IBCs or filamentous bacteria in their urine, but IBCs were found in nearly 1 in 5, and filamentous bacteria were in nearly half, of urine samples from the women with cystitis. All the urine samples that contained IBCs also contained filamentous bacteria. All of the women with IBCs and most of them with filamentous bacteria had E coli infections. Finally, the women with IBCs and filamentous bacteria in their urine had higher bacterial counts in their urine and had symptoms of cystitis for slightly longer than those without.
What Do These Findings Mean?
These findings suggest that the IBC cycle identified in mice occurs in at least some women with UTIs and may be associated with infections caused by E. coli. Because only one urine sample was collected from each woman, the cycle may be more common than these findings suggest. That is, in some cases the sample may have been taken at a time when there were no IBCs or filamentous bacteria in the urine. Also, because samples were taken at only one point in time, this study does not show whether intracellular bacteria persist and contribute to recurrent UTIs in women, as they appear to do in mice. To provide more information about the IBC cycle in people and its clinical relevance, additional studies are needed to examine whether there are any associations between the presence of IBCs and filamentous bacteria and treatment responses and recurrence, and to examine what is actually happening in the bladder during UTI. Until such studies are done, the clinical implications of the current findings remain uncertain. However, one possibility is that the presence of IBCs and filamentous bacteria in urine might identify people who would benefit from longer treatment with antibiotics or treatment with antibiotics that kill bacteria inside human cells.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040329.
The MedlinePlus encyclopedia contains pages on urinary tract infection, on cystitis, and on recurrent cystitis (in English and Spanish)
Information is available from the UK National Health Service Direct health encyclopedia on urinary tract infections and on cystitis
The US National Kidney and Urologic Diseases Information Clearinghouse provides information on urinary tract infections (in English and Spanish)
Information is available from the American Urological Association on urinary tract infections in adults
doi:10.1371/journal.pmed.0040329
PMCID: PMC2140087  PMID: 18092884
10.  Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial 
Objective To assess the cost effectiveness of different management strategies for urinary tract infections.
Design Cost effectiveness analysis alongside a randomised controlled trial with a one month follow-up.
Setting Primary care.
Participants 309 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection.
Interventions Patients were randomised to five basic management approaches: empirical antibiotics, empirical delayed (by 48 hours) antibiotics, or targeted antibiotics based on either a high symptom score (two or more of urine cloudiness, smell, nocturia, dysuria), dipstick results (nitrite or leucocytes and blood), or receipt of a positive result on midstream urine analysis.
Main outcome measure Duration of symptoms and cost of care.
Results Management with targeted antibiotics with midstream urine analysis was more costly over the period of one month. Costs for the midstream urine analysis and dipstick management groups were £37 and £35, respectively; these compared with £31 for immediate antibiotics. Cost effectiveness acceptability curves suggested that if avoiding a day of moderately bad symptoms was valued at less than £10, then immediate antibiotics is likely to be the most cost effective strategy. For values over £10, targeted antibiotics with dipstick testing becomes the most cost effective strategy, though because of the uncertainty we can never be more than 70% certain that this strategy truly is the most cost effective.
Conclusion Dipstick testing with targeted antibiotics is likely to be cost effective if the value of saving a day of moderately bad symptoms is £10 or more, but caution is required given the considerable uncertainty surrounding the estimates.
doi:10.1136/bmj.c346
PMCID: PMC2817048  PMID: 20139218
11.  Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients? 
SpringerPlus  2014;3:200.
Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.
Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 μl), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.
Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.
It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs.
doi:10.1186/2193-1801-3-200
PMCID: PMC4022969  PMID: 24839587
Intracellular bacteria; IBC; Pyuria; Urinary ATP; Bladder; Acridine orange stain
12.  Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review 
BMC Pediatrics  2005;5:4.
Background
Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture.
Methods
We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age.
Results
The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful.
Conclusion
Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation.
doi:10.1186/1471-2431-5-4
PMCID: PMC1084351  PMID: 15811182
13.  Can urine dipstick testing for urinary tract infection at point of care reduce laboratory workload? 
Journal of Clinical Pathology  2005;58(9):951-954.
Aim: The University Hospitals of Leicester NHS Trust microbiology laboratory receives 150 000 urine samples each year, approximately 80% of which prove to be culture negative. The aim of this study was to reduce the proportion of culture negative urines arriving in the laboratory, by producing local evidence based guidelines for the use of urine dipstick testing at point of care within the trust’s three acute hospitals.
Methods: One thousand and seventy six unborated urine samples were dipstick tested at the point of care using an automatic strip reader. Quantitative results for the four infection associated markers—leucocyte esterase, nitrite, blood, and protein—were compared with the results of conventional laboratory microscopy and culture.
Results: The performance of different marker combinations was calculated against the routine laboratory methods. One hundred and seventy five (16.3%) samples were negative for all four markers. Of these dipstick negative samples, only three (1.7% of all true positives) were positive by culture. The absence of all four infection associated markers was found to have a greater than 98% negative predictive value and a sensitivity and specificity of 98.3% and 19.2%, respectively.
Conclusions: A urinary dipstick testing algorithm for infection associated markers was derived for use in hospital patients to screen out negative urines. Two years after distributing the algorithm and promoting access to reagent strips and strip readers, a reduction in the urine workload has been seen against an otherwise increasing laboratory specimen load.
doi:10.1136/jcp.2004.025429
PMCID: PMC1770822  PMID: 16126876
algorithm; infection associated markers; urinary tract infection; urine dipstick testing; workload
14.  Urinary Tract Infections in Older Women 
JAMA  2014;311(8):844-854.
IMPORTANCE
Asymptomatic bacteriuria and symptomatic urinary tract infections (UTIs) in older women are commonly encountered in outpatient practice.
OBJECTIVE
To review management of asymptomatic bacteriuria and symptomatic UTI and review prevention of recurrent UTIs in older community-dwelling women.
EVIDENCE REVIEW
A search of Ovid (Medline, PsycINFO, Embase) for English-language human studies conducted among adults aged 65 years and older and published in peer-reviewed journals from 1946 to November 20, 2013.
RESULTS
The clinical spectrum of UTIs ranges from asymptomatic bacteriuria, to symptomatic and recurrent UTIs, to sepsis associated with UTI requiring hospitalization. Recent evidence helps differentiate asymptomatic bacteriuria from symptomatic UTI. Asymptomatic bacteriuria is transient in older women, often resolves without any treatment, and is not associated with morbidity or mortality. The diagnosis of symptomatic UTI is made when a patient has both clinical features and laboratory evidence of a urinary infection. Absent other causes, patients presenting with any 2 of the following meet the clinical diagnostic criteria for symptomatic UTI: fever, worsened urinary urgency or frequency, acute dysuria, suprapubic tenderness, or costovertebral angle pain or tenderness. A positive urine culture (≥105 CFU/mL) with no more than 2 uropathogens and pyuria confirms the diagnosis of UTI. Risk factors for recurrent symptomatic UTI include diabetes, functional disability, recent sexual intercourse, prior history of urogynecologic surgery, urinary retention, and urinary incontinence. Testing for UTI is easily performed in the clinic using dipstick tests. When there is a low pretest probability of UTI, a negative dipstick result for leukocyte esterase and nitrites excludes infection. Antibiotics are selected by identifying the uropathogen, knowing local resistance rates, and considering adverse effect profiles. Chronic suppressive antibiotics for 6 to 12 months and vaginal estrogen therapy effectively reduce symptomatic UTI episodes and should be considered in patients with recurrent UTIs.
CONCLUSIONS AND RELEVANCE
Establishing a diagnosis of symptomatic UTI in older women requires careful clinical evaluation with possible laboratory assessment using urinalysis and urine culture. Asymptomatic bacteriuria should be differentiated from symptomatic UTI. Asymptomatic bacteriuria in older women should not be treated.
doi:10.1001/jama.2014.303
PMCID: PMC4194886  PMID: 24570248
15.  A simple scoring system for evaluating symptoms, history and urine dipstick testing in the diagnosis of urinary tract infection 
Patients presenting with symptoms suggestive of urinary tract infection were recruited in a general practice survey aimed at measuring the predictive value of symptoms, history and urine dipstick testing for diagnosing the presence of bacterial infection. Urine specimens were obtained from 87% of the 521 patients recruited. A diagnosis of infection was established by urine culture producing a colony count in a pure culture exceeding 100 000 organisms per ml or between 10 000 and 100 000 organisms per ml plus a minimum of 100 leucocytes per mm3.
Occurrence rates for symptoms and other items of information in infected and non-infected groups were used to derive their positive and negative predictive values in making the diagnosis. The predictive value of volunteered symptoms was compared with that of elicited and volunteered symptoms combined. The positive predictive value of symptoms was increased where elicited symptoms were included but this was achieved at the cost of diminishing the negative predictive value. The occurrence rates were used to derive a mathematical model for diagnosing infection. The symptoms-history-urinalysis (SHU) score generated in this model compared well with a computer predicted probability. Both were substantially better than the assessment and action (decision to prescribe an antibiotic) of the recording doctor.
The scoring method described has been demonstrated in urinary tract infection but may be applied to any symptom combination related to a diagnosis for which there is an agreed definition.
PMCID: PMC1710747  PMID: 3316637
16.  Management of acute uncomplicated urinary tract infections in general practice in the south of The Netherlands. 
There is debate about the ideal diagnostic procedure for urinary tract infections (UTIs) in general practice. The aim of this study was to evaluate nitrite and leucocyte esterase strip test procedures in general practice patients, and to relate the results to the decision of the general practitioner to prescribe antibiotic therapy. A total of 292 female patients from eight general practices in the Maastricht area, who were aged 12 years or over with complaints suggesting UTI, were included in the study. All eight practices tested fresh urine samples using the nitrite strip test, and seven also used the leucocyte esterase strip test. The positive predictive value of the nitrite test was greater than the leucocyte test. Antibiotic therapy was nearly always prescribed when either or both of these tests were positive. Bacterial culture was positive in 159 (59%) cases, although treatment was started in 70 (27%) cases where there was an absence of significant bacteruria. It was found that the choice of agent used to treat the patient was related to the antibiotic susceptibility of the uropathogens that were isolated.
PMCID: PMC1313681  PMID: 10897517
17.  Response to antibiotics of women with symptoms of urinary tract infection but negative dipstick urine test results: double blind randomised controlled trial 
BMJ : British Medical Journal  2005;331(7509):143.
Objective To assess the effectiveness of antibiotic treatment of women with symptoms of urinary tract infection but negative urine dipstick testing.
Design Prospective, double blind, randomised, placebo controlled trial.
Setting Primary care, among a randomly selected group of general practitioners in Christchurch, New Zealand.
Participants 59 women aged 16-50 years presenting with a history of dysuria and frequency in whom a dipstick test of midstream urine was negative for both nitrites and leucocytes. Participants with complicated urinary tract infection were excluded.
Intervention Trimethoprim 300 mg daily for three days or placebo.
Main outcome measures Self reported diary of symptoms for seven days, recording the presence or absence of individual symptoms each day, followed by a structured telephone questionnaire after seven days. The main clinical outcome was resolution of dysuria at three and seven days and median time to resolution. Secondary outcomes were resolution of other symptoms.
Results The median time for resolution of dysuria was three days for trimethoprim compared with five days for placebo (P = 0.002). At day 3, five (24%) of patients in the treatment group had ongoing dysuria compared with 20 (74%) in the placebo group (P = 0.005). This difference persisted until day 7: two patients (10%) in the treatment group v 11 (41%) in the placebo group; P = 0.02). The number needed to treat was 4. The median duration of constitutional symptoms (feverishness, shivers) was reduced by four days.
Conclusions Although a negative dipstick test for leucocytes and nitrites accurately predicted absence of infection when standard microbiological definitions were used (negative predictive value 92%), it did not predict response to antibiotic treatment. Three days' treatment with trimethoprim significantly reduced dysuria in women whose urine dipstick test was negative. These results support the practice of empirical antibiotic use guided by symptoms. Balancing the competing interests of symptom relief and the minimisation of antibiotic use remains a dilemma—further research is needed to determine clinical predictors of response to antibiotics.
doi:10.1136/bmj.38496.452581.8F
PMCID: PMC558702  PMID: 15972728
18.  Does clinical examination aid in the diagnosis of urinary tract infections in women? A systematic review and meta-analysis 
BMC Family Practice  2011;12:111.
Background
Clinicians should be aware of the diagnostic values of various symptoms, signs and antecedents. This information is particularly important in primary care settings, where sophisticated diagnostic approaches are not always feasible. The aim of the study is to determine the probability that various symptoms, signs, antecedents and tests predict urinary tract infection (UTI) in women.
Methods
We conducted a systematic search of the MEDLINE and EMBASE databases to identify articles published in all languages through until December 2008. We particularly focused on studies that examined the diagnostic accuracy of at least one symptom, sign or patient antecedent related to the urinary tract. We included studies where urine culture, a gold standard, was preformed by primary care providers on female subjects aged at least 14 years. A meta-analysis of the likelihood ratio was performed to assess variables related to the urinary tract symptoms.
Results
Of the 1, 212 articles identified, 11 met the selection criteria. Dysuria, urgency, nocturia, sexual activity and urgency with dysuria were weak predictors of urinary tract infection, whereas increases in vaginal discharge and suprapubic pain were weak predictors of the absence of infection. Nitrites or leukocytes in the dipstick test are the only findings that clearly favored a diagnosis of UTI.
Conclusions
Clinical findings do not aid in the diagnosis of UTI among women who present with urinary symptoms. Vaginal discharge is a weak indicator of the absence of infection. The urine dipstick test was the most reliable tool for detecting UTI.
doi:10.1186/1471-2296-12-111
PMCID: PMC3207883  PMID: 21985418
19.  Leucocyte esterase test as rapid screen for non-gonococcal urethritis. 
Genitourinary Medicine  1987;63(6):380-383.
The two standard tests for the initial diagnosis of non-gonococcal urethritis (NGU), microscopic examination of gram stained urethral smears and the two glass urine test, have the disadvantage of being insensitive and subjective. The leucocyte esterase test detects enzymes specific to polymorphonuclear leucocytes and can therefore be used as a sensitive indicator of pyuria. This study sought to evaluate its use as a rapid, sensitive, and non-subjective method of screening for NGU. Of the 81 men with urethral symptoms in the study group, 26 had more than 5 polymorphonuclear leucocytes per high power field (x 1000) and all 26 were leucocyte esterase test positive; whereas 55 had fewer than 5 polymorphonuclear leucocytes per high power field, but 29 (53%) of them had a positive leucocyte esterase test result. In addition, 25 patients in the study group yielded Chlamydia trachomatis on culture. Of these 25, 24 (96%) were leucocyte esterase test positive, whereas only 11 (44%) were Gram stain positive. All 40 patients in the control group (without urethral symptoms or signs) were leucocyte esterase test negative. The leucocyte esterase test is thus a rapid, sensitive, and non-subjective screening aid in the diagnosis of NGU.
PMCID: PMC1194120  PMID: 3428895
20.  Parental reporting of smelly urine and urinary tract infection 
Archives of Disease in Childhood  2003;88(3):250-252.
Background: Parents often report that young children have "smelly urine" or a particular urinary odour. There is little evidence that these observations are relevant to the diagnosis of urinary tract infection (UTI).
Aims: To determine whether parental reporting of smelly urine is of any relevance to the diagnosis of UTI in children less than 6 years of age.
Methods: Parents whose children were having urine collected as part of their admission to a large district hospital were given a simple questionnaire to complete regarding the current smell of their child‘s urine. Parents were asked whether their child‘s urine smelled different from usual or had a particular smell. Microscopy and culture results of the child‘s urine were compared to their parent‘s questionnaire answers to see if there was a association between parental reporting of a different or particular urine smell and a diagnosis of UTI.
Results: One hundred and ten questionnaires and urine samples were obtained. Fifty two per cent of parents thought that their child‘s urine smelled different from usual or had a particular smell. Only 6.4% of children were diagnosed as having a UTI. There was no statistically significant association between parental reporting of abnormal urine smell and diagnosis of UTI.
Conclusion: In determining whether a young child has a UTI, asking parents about urine smell is unlikely to be of benefit.
doi:10.1136/adc.88.3.250
PMCID: PMC1719470  PMID: 12598394
21.  Urinalysis and Urinary Tract Infection: Update for Clinicians 
Dysuria is a common presenting complaint of women and urinalysis is a valuable tool in the initial evaluation of this presentation. Clinicians need to be aware that pyuria is the best determinate of bacteriuria requiring therapy and that values significant for infection differ depending on the method of analysis. A hemocytometer yields a value of ≥ 10 WBC/ mm3 significant for bacteriuria, while manual microscopy studies show ≥ 8 WBC/high-power field reliably predicts a positive urine culture. In cases of uncomplicated symptomatic urinary tract infection, a positive value for nitrites and leukocyte esterase by urine dipstick can be treated without the need for a urine culture. Automated urinalysis used widely in large volume laboratories provides more sensitive detection of leukocytes and bacteria in the urine.With automated microscopy, a value of > 2 WBC/hpf is significant pyuria indicative of inflammation of the urinary tract. In complicated cases such as pregnancy, recurrent infection or renal involvement, further evaluation is necessary including manual microscopy and urine culture with sensitivities.
doi:10.1155/S1064744901000412
PMCID: PMC1784655  PMID: 11916184
22.  Can the Griess Nitrite Test and a Urinary Pus Cell Count of ≥5 Cells Per Micro Litre of Urine in Pregnant Women be Used for the Screening or the Early Detection of Urinary Tract Infections in Rural India? 
Objectives
Urinary Tract Infection (UTI) is a common problem in pregnancy due to the morphological and the physiological changes that take place in the genitourinary tract during pregnancy. Screening methods may be useful, because a full bacteriological analysis could be reserved for those patients who are symptomatic or those who have positive screening test results. The exact prevalence of UTI in rural, pregnant women is unknown. The present study was undertaken to estimate the prevalence of UTI in pregnant women and for ascertaining the utility of the Griess Nitrite test and the Urinary Pus Cell Count of ≥5 cells per micro litre test for the screening or the early detection of UTI in them at primary health care clinics. Occurrence of urinary complaints was compared in UTI and non UTI women.
Method
We conducted a study on 300 randomly selected, pregnant women from rural areas. Urine cultures, pus-cell counts and the Griess nitrite test were used for diagnosis of UTI. The screening tests for UTI were evaluated in terms of their sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and the percentage of correctly classified.
Results
In the present study, the prevalence of UTI was found to be 29/300 (9.6%, 95% confidence interval 9.57-9.63). The specificities of the two screening tests were comparable (97.05% and 94.47%). Also, the negative predictive values of the two tests were almost similar (97.77% and 96.96%). The percentage of correctly classified by the Griess nitrite test and the urine pus cell count were found to be 95.33% and 92.33% respectively. The proportion of the women with various urinary complaints was significantly higher (P<0.00) in the UTI subjects as compared to that in the non-UTI subjects.
Conclusion
Urine culture remains the gold standard for the detection of asymptomatic bacteriuria. The Nitrite test of uncentrifuged urine was observed to be the best among the screening tests which were evaluated in terms of their efficiency and validity.
doi:10.7860/JCDR/2012/4565.2547
PMCID: PMC3527784  PMID: 23285444
UTI; Pregnancy; Rural; Urine Culture; Griess Nitrite test; Screening tests; Urinary Pus cell Test
23.  The value of urine specimens in screening for male urethritis and its microbial aetiologies in Tanzania. 
Genitourinary Medicine  1992;68(6):361-365.
OBJECTIVE--To evaluate the first void urine (FVU) specimen in screening for urethritis and its microbial aetiologies in a male African population in which urinary schistosomiasis is also prevalent. PATIENTS AND METHODS--Two hundred and forty eight males aged 15-54 years provided FVU specimens: 55 patients from a clinic for sexually transmitted diseases (STD), 151 patients from a medical outpatient clinic and 42 villagers from an area of high endemicity for S haematobium. Specimens were tested for leucocyte esterase (LE) using a dipstick (Nephur-Test+Leuco, Boehringer-Mannheim France SA). Ova of S haematobium were sought in terminal urine samples from all subjects. For all STD patients, and all medical outpatients with a positive LE test, urine and urethral swabs were tested for Chlamydia trachomatis antigen, and urethral swabs were tested for Neisseria gonorrhoeae by gram stain and isolation. RESULTS--The prevalence of LE positivity was 38/41 in STD patients with urethral signs or symptoms (93%), 5/14 among other STD patients (36%), 21/151 among medical outpatients (15%) and 13/42 among villagers (31%). As a screening test for urethral infection (detection of gonorrhoea or chlamydia and/or > or = 5 polymorphs per high power field on gram stain) the LE test had a sensitivity of 94% and a specificity of 53% among STD patients. Of 24 STD patients with gonococcal or chlamydial infection, 23 had a positive LE test (96%). Among general medical outpatients, 12 of 22 with a positive LE test had either conventionally defined urethritis or gonococcal or chlamydial infection, giving a positive predictive value of 55% for the LE test in this group. Of 18 subjects in all groups with urinary schistosomiasis nine had a positive LE test (50%), although three of these also had gonorrhoea. Chlamydial antigen was detected in the FVU specimen of all six subjects in whom it was detected in a urethral swab, and in an additional three subjects in the outpatient group. CONCLUSIONS--The FVU, which is an easily collected and non-invasive specimen, can provide valuable information on the prevalence of urethritis and on its microbial aetiology among the general male population in African countries.
PMCID: PMC1194970  PMID: 1487256
24.  Meta-analysis of Urine Heme Dipstick Diagnosis of Schistosoma haematobium Infection, Including Low-Prevalence and Previously-Treated Populations 
Background
Urogenital schistosomiasis remains highly endemic in Africa. Current control is based on drug administration, targeted either to school-age children or to high-risk communities at-large. Urine dipsticks for detection of microhematuria offer an inexpensive means for estimating infection prevalence. However, their diagnostic performance has not been systematically evaluated after community treatment, or in areas with continuing low prevalence. The objective of the present study was to perform meta-analysis of dipstick accuracy for S. haematobium infection in endemic regions, with special attention to performance where infection intensity or prevalence was low.
Methodology/Principal Findings
This review was registered at inception with PROSPERO (CRD42012002165). Included studies were identified by computerized search of online databases and hand search of bibliographies and existing study archives. Eligible studies included published or unpublished population surveys irrespective of date, location, or language that compared dipstick diagnosis of S. haematobium infection to standard egg-count parasitology. For 95 included surveys, variation in dipstick sensitivity and specificity were evaluated according to study size, age- and sex-specific participation, region, local prevalence, treatment status, and other factors potentially affecting test performance. Independent of prevalence, accuracy was greater in surveys of school-age children (vs. adults), whereas performance was less good in North Africa, as compared to other regions. By hierarchical ROC analysis, overall dipstick sensitivity and specificity for detection of egg-positive urine were estimated at 81% and 89%, respectively. Sensitivity was lower among treated populations (72%) and in population subgroups having lower intensity infection (65%). When the insensitivity of egg count testing was considered (and diagnosis inferred instead from combined hematuria and egg-count findings), overall dipstick sensitivity/specificity were 82%/97%, with significantly better sensitivity (92%) in high prevalence settings.
Conclusions/Significance
This analysis suggests that dipsticks will continue to serve as very useful adjuncts for monitoring community prevalence following implementation of population-based control of urogenital schistosomiasis.
Author Summary
Schistosomiasis is a chronic human disease caused by infection with multicellular trematode parasites of Schistosoma species. In particular, Schistosoma haematobium colonizes the veins in the pelvis, in and around the urinary tract, and causes inflammation that leads to ulceration and bleeding into the urine. One low-tech, inexpensive means of quickly identifying blood in the urine (hematuria) is to use a chemical reagent strip (dipstick) to test a patient's urine. While many studies have confirmed the usefulness of dipstick-detected hematuria as a proxy for infection in diagnosing infected people before treatment is given, their diagnostic performance after treatment has been uncertain. The current study systematically reviewed 95 available reports of dipstick performance in S. haematobium-endemic areas of Africa and determined, based on a meta-analysis of the primary data, that dipsticks appear to retain their diagnostic accuracy in low prevalence areas and after one or more rounds of treatment. This suggests that dipsticks will continue to be very useful tools in tracking and targeting regional requirements for treatment and prevention of S. haematobium infection as current school- and community-based programs go forward.
doi:10.1371/journal.pntd.0002431
PMCID: PMC3772022  PMID: 24069486
25.  Problems of basing patient recruitment for primary care studies on routine laboratory submissions 
Journal of Clinical Pathology  2007;60(11):1290-1293.
Background
Use of routine urine submission rates for estimation of patient enrolment in primary care studies of acute urinary symptoms may overestimate patient recruitment rate.
Aims
To compare the rates of submission of urines and significant bacteriuria from patients presenting with acute urinary symptoms in study general practices to routine microbiology laboratory urines.
Methods
Routine laboratory urine submissions were determined by counting all mid‐stream urine specimens submitted to the laboratory from 12 large general practitioner (GP) practices served by Gloucester and Southmead microbiology departments over two years (2000–02). Urine specimens were requested from all patients with acute urinary symptoms referred at research nurse practice visits over the same time period. The annual study urine submission was calculated using the ratio of the number of nurse practice visits to the annual number of possible consulting sessions. Significant bacteriuria was defined as a urine growing a single organism reported as >105 colony forming units/ml. Rates per 1000 patients were calculated using practice population data.
Results
The urine submission rate from study patients with acute urinary symptoms was one‐third the routine urine submission rate from the same practices. The significant bacteriuria rate attained from the study was less than half the routine significant bacteriuria rate.
Conclusion
Two‐thirds of routine urine samples submitted by GPs are probably not for the investigation of acute urinary symptoms. Basing consultation sample size power calculations for primary care studies or sentinel practice‐based surveillance in urinary tract infection on routine laboratory submissions is unreliable and will lead to significant overestimation of recruitment rate.
doi:10.1136/jcp.2007.046854
PMCID: PMC2095479  PMID: 17337588

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