Rapid UTI Screening Test
Support Book May 2007
Confidential
Dear Distributor,
This book is meant to give you comprehensive information about our products, so that you will be able to understand their characteristics with respect to the competition and allows you to build the proper argumentation to make your customers choose us. You will find, besides the clinical background and technical information on the product, reports from different studies showing the strong, but in some instances also the weak points of our system. Some material should be used for your knowledge only, in order to handle objections properly (this is why the whole book is marked “confidential”).
We strongly suggest that you carefully read all the chapters and select only the suitable ones when you need to hand copies to customers.
This support book will be periodically updated. Please let us have your comments and we will try to include the information requested in the next versions.
Thank you for your cooperation.
Best regards,
Savyon Marketing Team
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Table of contents:
1. Urinary Tract Infections (UTI) – Overview ...... 4
General Background ...... 4 Epidemiology ...... 4 Urinary Pathogens...... 5 URISCREEN™ – Rapid UTI screening test ...... 7 2. URISCREEN TM Product ...... 8
Assay Procedure...... 11 3. Performance Characteristics...... 13
Preface...... 13 Clinical Studies...... 14 Interference Studies...... 21 4. Competition ...... 25
5. Positioning and Strategy ...... 26
Marketing Guide...... 28
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1. Urinary Tract Infections (UTI) – Overview
1. 0 General Background
What is a UTI?
• Bacterial Infection of the Urinary Tract
• Occurs predominantly in women and elderly
• The major causative pathogen - bacteria
• Traditionally diagnosed by clinical laboratory in culture (24-hour turnaround)
Urinary tract infections are among the most common infections in humans. The majority of cases are caused by a limited number of bacterial genera. The presence of these bacteria in urine is termed bacteriuria . Significant bacteriuria ( ≥10 5 cells/ml of urine) defines the number of bacteria in midstream, clean voided urine that exceed the numbers usually caused by contamination.
Urinary tract infection implies a bacterial attack on tissue located anywhere from the renal cortex in the kidney (upper tract infections), to the bladder (lower tract infections). It is generally accepted that urinary tract infections are usually a consequence of ascending infection by microorganisms from the lower tract into the upper tract. Reflux of urine into the urethra and up into the renal pelvis is probably an important mechanism for introducing organisms into the upper tract. Differentiation between lower and upper infections is difficult. Most urinary tract infections are asymptomatic. One third of the patients with asymptomatic bacteriuria have an upper tract infection.
Clinical symptoms include:
• Urgency and/or frequency in urinating • Fever • Increased Erythrocyte sedimentation rate • Urine sediment of Leukocytes, Bacteria and Erythrocytes
1. 1 Epidemiology
Frequency of bacteriuria in neonates is about 1% and more common in boys than in girls.
Frequency of bacteriuria in adult men is less than 1%. 4 03-05/07
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After age of 65, bacteriuria frequency increases and reaches 5-10% at the age of 80. This increase is attributed at least in part to the development of prostatic hypertrophy and obstruction of the bladder outlet. Frequency of bacteriuria in women increases with the increasing of age. In school girls infectious rate is about 1%, and in young women the range is between 1-3% with at least 10-20% of adult females experiencing a symptomatic infection at some time during their life. In elderly woman the frequency increases to about 20%.
1. 2 Urinary Pathogens
Urinary pathogen microorganisms have been well recognized. The following list includes those known to cause infection by the ascending route (by the urethra):
Gram-Positive and Gram-Negative Bacteria
Gram-negative bacilli Enterobateriaceae Escherichia coli Proteus spp. Klebsiella spp. Citrobacter spp. Serratia spp. Enterobacter spp. Providencia spp. Pseudomonaceae Pseudomonas spp. Alcaligenes spp.
Gram-negative coccobacilli Acinetobacter spp.
Gram-Positive cocci Micrococcaceae Staphylococcus aureus Staphylococcus saprophyticus Staphylococcus epidermidis
Streptoccaceae Streptococcus faecalis Staphylococcus agalactiae
Fungi Candida spp. Torulopsis glabrata
The majority of these organisms are facultative anaerobes - they can grow either in the presence or absence of molecular oxygen. Most of them originate in the commensal flora of the bowel. Some, including Staphylococcus epidermidis, group B Streptococci, Candida and Torulopsis 5 03-05/07
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probably originate in the flora of the vagina or perineal skin in females, or the perpetual sac in males.
Escherichia coli is the most common urinary pathogen.
Much less common infections outside hospitals are due to Proteus spp ., Staphylococcus saprophyticus , Klebsiella spp ., Staphylococcus faecalis and Lancefield group-B hemolytic streptococci.
Different Pathogens infect different age and sex groups
While E. coli is undoubtedly the most common urinary pathogen over all, it is not surprising, in view of the anatomical and physiological differences between males and females, that there are differences in the infecting organisms in particular age and sex groups. In neonatal infection, when the route of infection may be haematogenous, the most common infecting organism in both sexes is E.Coli. During childhood, however, there are marked differences: The frequency with which Proteus spp . causes infection in boys is striking. This is possibly due to the presence of this pathogen in the perpetual sac, the urethra, or even the prostatic ducts. Proteus becomes much less common in adult males, only to reappear in old age, suggesting that prostatic function may play a part in maintaining an environment in the urethra, which is unfavorable to this species. E.Coli infection occurs throughout all age groups. Staphylococcus saprophyticus is the second most common urinary pathogen in young women between 15 and 35 years of age, and may be associated with sexual intercourse. It has been demonstrated in the rectal flora of adult women, and infection may therefore arise in the same way as E. coli infections. Strains of Staphylococcus epidermidis , which are usually commensal in the urethra, may colonize in the bladder, sometimes causing urinary symptoms and systemic upset, in patients who are catheterized. These incidents are very common in elderly patients undergoing urological procedures, or in patients of both sexes who are catheterized for relief of obstruction or incontinence. Staphylococcus epidermidis may also cause infection in patients with renal scars or stones, who have been subjected to repeated courses of antibacterial treatment.
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In Summary:
Different pathogens infect different age and sex groups, as a result of a combination of factors:
• The comensal flora of the anatomical areas from which ascending infection may occur. • The presence of antibacterial factors in, for instance, prostatic fluid, or produced by uroupithelium and probably influences of different sexual hormones. Mechanical factors such as catheterization.
1. 3 URISCREEN™ – Rapid UTI screening test
URISCREEN is a rapid screening test for the detection of bacteriuria and somatic cells in urine. It is simple, highly sensitive and conclusive. This makes it ideally suited for routine testing in schools, industrial plants hospitals, clinics and physicians’ offices. Independent clinical studies have demonstrated that URISCREEN is exceptionally sensitive and will indicate positive at concentrations of 5 x 10 4 CFU/ml with at least 95% negative predictive value.
URISCREEN meets the need for faster and less costly screening procedures by providing both physicians and laboratories with a quick, efficient tool. As the URISCREEN test can be conducted on the spot, therapy may be initiated without delay, or the patient referred for further testing.
These features now give physicians an efficient tool for the routine testing of asymptomatic populations, particularly pregnant women and elderly patients.
Laboratories now have precise and rapid procedure to screen out the negatives. This increases throughout, enabling immediate evaluation, where indicated. URISCREEN is therefore highly cost-effective.
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2. URISCREEN TM Product
Ordering Information:
101-01 URISCREEN TM test kit for 20 determinations
URISCREEN is a rapid UTI screen test for bacteriuria and presence of somatic cells in urine.
Kit design:
20 Stoppered test tubes, each containing 35-50 mg URISCREEN TM reagent powder
1 Dropper bottle containing 10 ml of hydrogen peroxide solution
20 Disposable 2 ml pipettes or no pipettes
1 Instruction manual
Intended use:
URISCREEN is a rapid screening test for UTI. The test is primarily intended for the screening of asymptomatic populations (e.g., routine testing in schools, industrial plants, institutions, hospitals, clinics, physicians’ offices, etc.) for significant bacteriuria, hematuria, pyuria, and the presence of other somatic cells in urine. The URISCREEN is intended for both professional and over the counter use. A POSITIVE RESULT INDICATES THAT THE URINE REQUIRES FURTHER LABORATORY EXAMINATION FOR MORE DETAILED DIAGNOSIS. The URISCREEN ™ kit has been granted the waiver status by the FDA, therefore a QC negative and positive control should be run only once a new lot is opened. The URISCREEN ™ kit has been approved by FDA as an over the counter (OTC) product.
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How does the test work?
URISCREEN detects Catalase. The presence of catalase in the urine serves as an indication for bacteria and/or white blood cells present in your urine. Both white blood cells and bacteria are commonly found in urine during a Urinary Tract Infection.
To test, collect a urine sample in a collection cup, add urine to a URISCREEN Test Tube. Urine is added up to the line that is printed on the stand. Add four drops of hydrogen peroxide solution to the Test Tube. Mix gently. Read the results in 2 minutes.
If foam is seen the test is positive for Catalase. A positive test means there may be bacteria and/or white blood cells in the urine and that you may have a Urinary Tract Infection.
If there is no foam the test is negative for Catalase. Normally, there should not be any bacteria or white cells in urine.
Shelf life and correct storage
Shelf life of URISCREEN is 36 months at room temperature.
URISCREEN is stored at room temperature (15-28°).
URISCREEN should not be exposed to high temperature (above 37°C).
Sample Collection
Urine is normally a sterile body fluid. Urine that is not properly collected may become contamined with flora from the urethra, vagina, prostate or perineum.
Routinely, urine samples must be collected by obtaining the mid-stream urine flow by the clean-catch technique:
• The priuretheral area and the perineum are first cleaned. • The first volume of urine is discarded and washes away the surface commensals from the distal urethra.
The midstream specimen is collected for examination (this specimen is assumed to represent the true microbiological situation in the bladder).
Whenever possible, first voided morning urine should be collected.
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If not possible, urine should be allowed to incubate in the bladder for as long as possible before collection to increase the number of organism in the sample.
Urine collection from babies is performed by adhering a special sterile urine collection bag to the genitals.
Special collection techniques like suprapubic aspiration (using a needle for direct aspiration from the bladder), and catheterization are reserved to those patients who are unable to produce a midstream samples.
Transportation of urine specimens to the laboratory
Urinary tract pathogens grow in urine; therefore, collected specimens should be processed within 2 hours after collection to achieve accurate results. In case of delayed transportation to the laboratory, special urine collection kits were designed to maintain the bacterial population in urine at room temperature for 24 hours, however, refrigeration at 4°C is widely accepted as satisfactory for this purpose.
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Assay Procedure
1. Transfer urine from a collection cup into the URISCREEN test tube, filling it up to the line on the stand (approximately 1.5-2ml). Mix gently URISCREEN test tube for few seconds so that powder dissolved and solution turned blue.
2. Add 4 drops of hydrogen peroxide solution, using the dropper bottle included. Shake to tube.
3. Read the result after 2 minutes.
Reading Results
Positive Result: If white foam appears on top of the blue liquid after 2 minutes, the test is positive. You may have bacteria and/or white blood cells in your urine.
Negative result: If no white foam appears on top of the blue liquid after 2 minutes, the test is negative. It is not likely to have bacteria and/or white blood cells in urine.
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When to use the test:
Symptoms for possible UTI infection include:
• Burning • Frequent urination • Cloudy urine • Abdominal pain or discomfort • Fever • Lower back pain
Limitations
1. False negative results could occur if bacteria are Catalase negative.
2. False negative results could be related to frequent urination (urine not held in the bladder for at least four hours). There may not be enough bacteria in the urine to produce Catalase activity.
3. Other cells present in urine could cause false positive results.
4. Women should not perform the test during their menstrual cycle. Blood in urine may cause false positive results.
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3. Performance Characteristics
3. 0 Preface
In order to compare the performance of a new test to that of a reference test, sensitivity and specificity should be calculated.
Sensitivity is the ability of a test to detect the positive population as determined by a reference method.
Sensitivity = True positives x 100 (True positives + false negatives)
Specificity is the ability of a test to detect the negative population as determined by a reference method.
Specificity = True negatives x 100 (True negatives + false positives)
Accuracy = Is the ability of a test to correctly detect the test population as determined by a reference method
Accuracy = True positives + True negatives x 100 (Total no. of specimens)
True Positive = Those samples which are positive by the tested method and by the reference method.
True Negative = Those samples which are negative by the tested method and by the reference method.
False Positive = Those samples which are positive by the tested method and negative by the reference method.
False Negative = Those samples which are negative by the tested method and positive by the reference method.
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3. 1 Clinical Studies
Studies have been done to confirm the performance of the URISCREEN ™ either by professional or by consumers. The performance of URISCREEN kits were evaluated as compared to Culture use for the determination of bacterial colony (bacteriuria) together with counting of somatic cells by microscopic method (pyruria), to Nitrite test and to Leukocyte esterase which are commonly used for the detection of UTI.
3.2.1 Studies conducted by laboratory technician (Professional):
••• Comparison between URISCREEN and the common techniques based on bacterial colony counting on agar plates and counting of somatic cells by microscopy.
A. In a comparative study 2369 urine specimens were randomly collected in a period of six months. Bacterial counts were determined by plating on MacConkey and blood agar plates. Somatic cells were counted microscopically. In parallel the specimens were also tested by the URISCREEN test. The results are given in the following table:
Table No. 1:
Results with URISCREEN Bacterial counts Somatic cells (CFU/ ml) POSITIVE NEGATIVE
<10,000 - 170 913 + 438 262
10,000-50,000 - 43 33 + 63 10
>50,000 - 98 33 + 289 17
Specificity and sensitivity were calculated for two cutoff levels of bacterial counts: >10,000 CFU/ml and >50,000 CFU/ml. Since it has been well recognized that evaluation of asymtomatic urine specimens for infection should include both bacteriuria and pyuria , specimens with significant number of Somatic cells (>10 cells per high power field), as determined by microscopic counting, were considered as true positives even if bacterial counting showed less than 10,000 CFU/ml. Specimens containing
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<10,000 or <50,000 (depending on the cutoff level considered) CFU/ml without somatic cells were considered true negatives.
The sensitivity and specificity obtained are:
1. For bacteriuria cutoff level at >10,000;
Sensitivity = 90% Specificity = 87% Accuracy = 88%
1. For bacteriuria cutoff level at >50,000:
Sensitivity = 94% Specificity = 86% Accuracy = 89%
B. In another comparative study 976 urine specimens from asymptomatic population were collected. Bacterial counts were determined by colony counting on MacConkey and Cled agar plates on dip slides. Somatic cells were counted microscopically.
The results in comparison with those obtained by the URISCREEN test, are depicted in the following table:
Table No. 2:
Results with URISCREEN Bacterial counts Somatic cells (CFU/ ml) (*) POSITIVE NEGATIVE
<50,000 - 95 462 + 236 8 >50,000 + and - 160 15
(*) Consider negative if sample contains less than 10 Somatic cells per high power field.
In calculating specificity, sensitivity and accuracy, specimens are considered positive if they contain more than 50,000 CFU/ml and/or >10 Somatic cells per high power field.
The results obtained are: Sensitivity = 94% Specificity = 83% Accuracy = 88%
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Conclusions:
The results of the comparative studies depicted above show that high sensitivity, specificity and diagnostic efficiency values were obtained with URISCREEN for the two cutoff levels of bacterial counts taken: >10,000 and >50,000 CFU/ml. These high values partly result from the fact that URISCREEN is a test for both bacteriuria and presence of somatic cells in urine. In the comparative studies conducted URISCREEN was evaluated relative to the common and fundamental techniques for determination of bacterial counts by colony counting on agar plates and counting of somatic cells by microscopy.
The results obtained support our claim that URISCREEN is substantially equivalent to these routine techniques that have been most widely used in clinical laboratories for the detection of significant bacteriuria, pyuria, hematuria and presence of somatic cells in urine.
••• Comparison of URISCREEN to reference culture results
To demonstrate the performance of the URISCREEN , results were compared to reference culture results. The same samples were tested by both LE and by Nitrate methods. 139 patients with symptoms of Urinary Tract Infection or those suspected of having a Urinary Tract Infection were screened in this study. This study was performed in the USA.
URISCREEN results were compared to culture results. A positive culture is defined as having a colony count of 100,000 CFU/ml
Table No. 3:
Culture Positive Culture Negative Total URISCREEN Positive 41 26 67 URISCREEN Negative 2 70 72 Total 43 96 139
Sensitivity = 95.35% Specificity = 72.92% Accuracy = 79.86%
These data confirm that URISCREEN is a reliable system for the screening of patients for Urinary Tract Infection.
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Comparison of competitive methods to urine culture
••• Comparison of Leukocyte esterase (LE) to reference culture results.
Table No. 4:
Culture Positive Culture Negative Total LE Positive 38 43 81 LE Negative 4 54 58 Total 42 97 139
Sensitivity = 90.48% Specificity = 55.67% Accuracy = 66.19%
Comparison of Nitrite to reference culture results
Table No. 5:
Culture Positive Culture Negative Total Nitrite Positive 16 2 18 Nitrite Negative 27 94 121 Total 43 96 139
Sensitivity = 37.21% Specificity = 97.92% Accuracy = 79.14%
Conclusions:
Based on our protocol, a positive culture was defined as having a colonies count of ( ≥ 100,000) CFU/ml.
URISCREEN demonstrated 95% Sensitivity when compared to culture.
Leukocyte esterase demonstrates only 90% Sensitivity when compared to culture and Nitrite sensitivity was only 37%.
If a positive culture is considered to be ≥10 3 CFU/ml, URISCREEN demonstrates improved specificity of 87%, with a sensitivity of 82%.
Two specimens were URISCREEN negative and Culture positive. These specimens are likely to be false negative results. 17 03-05/07
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Based on the data provided, URISCREEN is a better indicator of UTI than either Leukocyte esterase (Sensitivity 90%) or Nitrite (Sensitivity 37%) based on positive culture results ( ≥ 100,000 CFU/ml).
False negative results are rarely observed (only 2 of the 139 specimens tested were confirmed to be culture positive and URISCREEN negative).
URISCREEN is a reliable system for screening patients for Urinary Tract Infection.
3.2.3 Studies conducted by consumers:
All studies were conducted in USA.
Consumer URISCREEN results were compared to reference culture results. A positive culture result was defined as having a colonies count ≥≥≥ 100,000 CFU/ml.
Culture vs. URISCREEN (performed and read by Consumer)
Table No. 6:
Culture Positive Culture Negative Total URISCREEN Positive 11 12 23 URISCREEN Negative 0 69 69 Total 11 81 92
Sensitivity = 100% Specificity = 85.19% Accuracy = 86.96%
It should be noted of the 12 false positive URISCREEN results, 6 had urine colonies counts of >10,000 and <100,000 CFU/ml. Based on our protocol criteria these urine samples were considered negative. The test is meant to be used for screening only and is meant to alert the consumer of a potential infection.
The product alerts a patient of a potential problem, which has to be investigated by a physician.
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Culture vs. URISCREEN (performed and read by Medical Technician)
Table No. 7:
Culture Positive Culture Negative Total URISCREEN Positive 11 8 19 URISCREEN Negative 0 73 73 Total 11 81 92
Sensitivity = 100% Specificity = 90.12% Accuracy = 91.30%
URISCREEN test results were compared to Bayer Multistix Nitrite/LE test results. Multistix result was considered positive if either the Nitrite or LE were positive.
Multistix Nitrite /LE vs. URISCREEN (performed and read by Consumer)
Table No. 8:
Mutistix Positive Multistix Negative Total URISCREEN Positive 13 10 23 URISCREEN Negative 0 69 69 Total 13 79 92
Sensitivity = 100% Specificity = 87.34% Accuracy = 89.13%
Multistix Nitrite /LE vs. URISCREEN (performed and read by Med Tech)
Table No. 9:
Mutistix Positive Multistix Negative Total URISCREEN Positive 13 6 19 URISCREEN Negative 0 73 73 Total 13 79 92
Sensitivity = 100% Specificity = 92.41% Accuracy = 93.48% 19 03-05/07
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URISCREEN was compared to Uri-Test a Nitrite test, manufactured by TCPI. Uri-Test is approved for OTC sales as a rapid test for Urinary Tract Infection.
Uri-Test Nitrite in Urine vs. URISCREEN (performed and read by Consumer)
Table No. 10:
Uri-Test Positive Uri-Test Negative Total URISCREEN Positive 12 9 21 URISCREEN Negative 3 68 71 Total 15 77 92
Sensitivity = 80% Specificity = 88.31% Accuracy = 86.96%
Conclusions:
URISCREEN ™ is a good method for screening for UTI. The product provides an effective and safe method for home testing Urinary Tract Infection. Consumers found the product easy to use and had almost no difficulties in performing the test. Data clearly demonstrates that the product can be used as a screening test to alert consumers of potential infection. Although white and/or red blood cells can cause a false positive URISCREEN ™ results, blood in the urine is not normal (except possibly during menstruation). Therefore customers should be alerted to a potential abnormality and should seek medical attention.
3.2.3 Summary of studies for both professionals and consumers
All the studies clearly demonstrate that URISCREEN is an easy-to-use, accurate method for screening urine for the detection of urinary tract infection. The method is safe and effective and can be used satisfactorily by medical technicians and by consumers.
The studies confirm the performance of URISCREEN and demonstrate that URISCREEN is more sensitive than Nitrite and Leukocyte esterase (LE) tests.
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3. 2 Interference Studies
To demonstrate that commonly encountered substances do not interfere with the performance of the URISCREEN test a variety of interference studies were completed. The following is a summary of the interference studies done.
Table No. 11:
Potentially Interfering Catalase IU/ml Substance 0 0.2 0.4 0.8 1.6 Acetaminophen 20m/dl - - + + + Ascorbic Acid 20/mg/dl - - + + + Caffeine 20mg/dl - - + + + Glucose 2g/dl - - + + + Ampicilin 20mg/dl - - + + + Acetylsalicylic Acid 20mg/dl - - + + + Atropine 20mg/dl - - + + + Gentisic Acid 20mg/dl - - + + + Hemoglobin 1mg/dl - - + + + Tetracycline 20mg/dl - - + + +
Conclusions :
Commonly encountered substances that potentially could interfere with the URISCREEN do not affect the final test result.
In each case, no interference with the expected URISCREEN result was observed.
The level of interfering substances tested was determined to be in excess of what would be excreted after 8 hours by the human kidney.
Additional interference studies were done to demonstrate that substances commonly found in urine do not interfere with URISCREEN performance:
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Potential Interference of Protein in Catalase Positive and Negative Urine
Table No. 12:
Catalase Concentration Protein Protein Protein Protein IU/ml 0 mg/dl 0.5 mg/dl 15 mg/dl 30 mg/dl 0 - - - - 0.2 U/ml - - - - 0.4 U/ml - - - - 0.8 U/ml + + + + 1.6 U/ml + + + +
Conclusion: Proteins at levels of 30 mg/dl or below, do not affect URISCREEN test results.
Potential Interference of pH Variance in Catalase Positive and Negative Urine
Table No. 13:
Catalase Concentration pH pH pH pH pH IU/ml 5.0 6.0 7.0 8.0 9.0 0 - - - - - 0.2 U/ml - - - - - 0.4 U/ml + + + + + 0.8 U/ml + + + + + 1.6 U/ml + + + + +
Conclusion : pH range of 5.0-9.0 does not affect the URISCREEN results.
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Potential Interference of Specific Gravity Variance in Catalase Positive and Negative Urine
Table No. 14:
Catalase Concentration Specific Specific IU/ml Gravity Gravity 1.005 - 1.030 1.140 0 - - 0.2 U/ml - - 0.4 U/ml + + 0.8 U/ml + + 1.6 U/ml + +
Conclusions:
Specific gravity of 1.005 - 1.140 does not affect URISCREEN test results.
Potential Interference of Hemoglobin in Catalase Positive and Negative urine
Table No. 15:
Catalase Concentration Hemoglobin Hemoglobin Hemoglobin IU/ml 5 mg/dl 1.5 mg/dl 30 mg/dl 0 - - - 0.2 U/ml - - - 0.4 U/ml + + + 0.8 U/ml + + + 1.6 U/ml + + +
Conclusions:
There is no effect of Hemoglobin at levels of 30 mg/dl on the URISCREEN results.
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Potential interference of Ascorbic Acid on Catalase Positive and Negative Urine
Table No. 16:
Catalase Concentration Ascorbic Acid Ascorbic Acid IU/ml 0 mg/dl 25 mg/dl 0 - - 0.2 U/ml - - 0.4 U/ml + + 0.8 U/ml + + 1.6 U/ml + +
Conclusions:
There is no effect of Ascorbic Acid at levels of 25 mg/dl on the URISCREEN test results.
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4. Competition
URISCREEN and other UTI rapid tests are being used both professionally and over-the-counter for the detection of bacteria and/or white blood cells in urine. URISCREEN determines Catalase activity while other rapid tests technologies are based on the detection of Nitrite or Leukocyte esterase in the urine.
Manufacturer: Technical Chemical and Product, Inc. (TCPI) Product: Uri-Test TM Nitrite in Urine-Urine Nitrite Test strip for the detection of urinary tract infection
Uri-Test Nitrite in Urine is a rapid test for the detection of Urinary Tract Infection. Uri-Test Nitrite in Urine is approved also for over- the- counter sale to the lay consumer.
Manufacturer: Bayer Diagnostics Product: MultiStix TM -Urine Test Strip that includes a test for the detection of Nitrite and Leukocyte esterase. Nitrite is an indicator of bacteria in urine, while Leukocyte esterase is indicator of white blood cells in urine.
Filtracheck (Meridian)
Dipstick Urinalysis (Bayer, etc)
Method Comparison
Product Method Accuracy % URISCREEN Catalase 92-95 Filtracheck Filtration 92-95 Urine Dipstick Biochemical 65-70
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5. Positioning and Strategy
5. 0 UTI Testing Market
• ~ 300 million UTI dipstick tests are performed each year
- $ 100 million market
• Over 65 million UTI culture tests are performed each year.
- $ 40 million market
The Screening Concept
~ 70% of urine samples are negative
Screening allows immediate determination of negatives
• saves time • reduces overall treatment cost • prevents unnecessary medication
URISCREEN Detects enzymes present during UTI term present in urine bacteriuria bacteria pyuria leukocytes (WBC) hematuria erythrocytes (RBC)
UTI Markets
Clinical Laboratories
Alternate Testing Sites (ATS)
Consumer Market - Over the Counter (OTC)
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ATS: Target Markets
Target Population Target Market ------Elderly Nursing Homes (age >65) Home Care (VNA, etc) Primary Care/General Practice
Women OB/GYN (age 18-45) Doctors’ Offices Primary Care/General Practice
ATS: Market Population UTI tests Target Incidence per year Population (est. million) ------
Elderly 10-20% 10 (age >65)
Women 25-30% 39 (age 18-45)
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5. 1 URISCREEN™ Advantages
Accurate
Easy-to-use
Rapid, Visual results
Cost-effective
Broad market potential
5. 2 Patent Status
Savyon Diagnostics Ltd. has exclusive worldwide rights to the patented technology.
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5. 3 Marketing Guide
1. Describe the four steps of the procedure a. Add urine to the tube b. Add 4 drops of H 2O2 c. Mix gently d. Read
2. What are the four most important features of the system? • Rapid: 1-2 minutes • High sensitivity and high negative predictive value (NPV) • Detects both bacteriuria and pyuria (presence of WBC) = true infections • No instrumentation needed • Inexpensive • User friendly
3. Name five competitive systems: • Standard culture • Dipslides • Dipsticks • Filtracheck • Bac-T-Screen • UID/Vitek • LAD • Gen Probe
4. List three disadvantages of Bac-T-Screen and three disadvantages of dipsticks:
Bac-T-Screen: • Non-specific particles cause false positives • Antibiotics, dyes or medications can cause false positive reactions • Instrument needed • Only 2 tests can be processed at one time
Dipsticks: • Colors hard to read • Yeasts and enterococci do not reduce nitrate • Antimicrobials, other medications and nitrite in diet can cause false positive reactions. • Preservatives can not be used in transportation
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5. What does a positive URISCREEN result indicate?
Presence of bacteria and/or somatic cells in urine.
0. What bacteria are catalase negative and how does URISCREEN perform with them?
Streptococci, most notably enterococci, are catalase negative. URISCREEN will be positive if these bacteria cause true infections and white cells are present in the specimen.
7. How do you explain a culture negative, URISCREEN positive result? • Fastidious organisms, such as Chlamydia, Trichomonas, Ureaplasma, which do not grow on culture plates, may have caused the infection and white cells are present in urine. • Bacterial count might be low because of current or prior antibiotic therapy, but white cells are still present. • Contamination of specimen with RBC (red blood cells) because of trauma or menstrual cycle in females. • Presence of Epitelial cells (EPC) due to poor collection technique
8. How long can you store a urine specimen before doing the URISCREEN test? • 2 h without refrigeration • Up to 6 h when kept in the refrigerator • Up to 12 h at RT in boric acid transport tubes
0. How about URISCREEN with immunocompromised patients? • immunocompromised patients have lower levels of white cells, less then 5,000/ l as compared to 5,000-10,000 cells/ l in normal people. Their immunoresponse is less aggressive, low levels of white cells still may be present in urine and turn the URISCREEN test positive. On the other hand, significant levels of bacteria in urine will cause a positive reaction. A few cases where white cell level is not high enough and catalase negative bacteria are causing the infection may be missed.
1. What does a culture positive result mean? • It means that bacteria were present in urine at the time of specimen collection. It does not necessarily mean that true infection is going on, bacteria can be present because of contamination or colonization. Only presence of white cells
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and clinical symptoms can confirm that a true infection is going on.
11. What kinds of components are included in the reagent powder? • Buffering agents to bring the pH of urine to an optimal range, for maximum catalase activity. • Components that affect the cell wall releasing the catalase enzyme for reaction with H 2O2 . • Detergents to trap the oxygen and form a stable foam • A dye to visualize that mixing was done properly and to make reading easier
12. Is the quantity of foam indicative of bacterial concentration? • No, since the quantity of foam produced does not reflect the presence of bacteria only, but also presence of somatic cells. Also, the catalase activity varies between different bacterial species and between metabolic stages of bacteria.
13. List three reasons why culture is not a 100% gold standard for UTI: • Some organisms do not grow in culture • Culture does not differentiate between true infection and contamination or colonization. • Volume delivered by a calibrated loop might vary between 50-150% • One positive culture predicts presence of infection in 80% of patients only, two in 96%.
14. What does Predictive Negative Value (PNV) mean? • It describes the confidence level for reporting negative results: What percentage of URISCREEN negative results were true negatives.
15. Why should urine, seeded with bacteria not be used to monitor 5 URISCREEN performance at 10 CFU/µl level? • Only small proportions of the cells, in an overnight colony are in a metabolically active stage. So, if the turbidity of the suspension is adjusted to 10 5 CFU/ /µl level, the metabolically active population is much
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lower in number and a negative result might be obtained. However, if the organisms are grown in broth and harvested in the logarithmic growth phase, they are metabolically active and will give a positive result at the cutoff level.
16. What conclusions can we draw from the URISCREEN evaluations presented at the 1991 ASM and ICAAC meetings: • URISCREEN detects true infections with high sensitivity and high NPV. • URISCREEN is as good as or better than any of the other screening methods on the market.
17. Why is necessary to have a method to detect somatic cells during clinical evaluations? • Somatic cells, WBC and RBC are catalase positive. In case of fastidious organisms which don’t grow in culture. URISCREEN is positive because of presence of WBC. RBC might be present in catheterized urine or specimens taken during menstruation. EPC might be present because of poor specimen collection technique. All these might be regarded as false positives if only compared against culture. Contaminants, which do not induce a white cell response, might be detected with URISCREEN .
18. How should URISCREEN results be reported out? • Negative by a urine screen method. • Positive by a urine screen method, culture to follow.
Note: A positive screening result indicates presence of bacteria and/or somatic cells.
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Publications:
1. S. A. Berger, B. Bogokowsky and C. Block: Rapid screening of urine for bacteria and cells by using a catalase reagent. Journal of Clinical Microbiology, May 1990 p. 1066-1067.
2. K. C. Carroll, M. D. Devon, C. Hale, D. H. Von Boerum, G. C. Reich, L. T. Hamilton and J. M. Matsen: Laboratory evaluation of urinary tract infections in an ambulatory clinical. American Journal of Clinical Pathology. January 1994. Vol. 101 No. 1
3. Z. Hagay, R. Levy, A. Miskin, D. Milman, H. Sharabi and V. Insler: Uriscreen, a rapid enzymatic urine screening test: Useful predictor of significant bacteriuria in pregnancy. Obstetrics & Gynecology. March 1996. 87: 410-413.
4. M. T. Pezzlo, D. Amsterdam, J. P. Anhalt, T. Lawrence, N. J. Stratton, E. A. Vetter, E. M. Peterson and L. M. De La Maza: Detection of bacteriuria and pyuria by Uriscreen, a rapid enzymatic screening test. Journal of Clinical Microbiology, March 1992 30: 680-684.
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