Rines y Llantas

How Long Is Valium Detected In Urine?

• Renato Leandro
• 26.07.2023
• 0
• 17

What drugs will test positive for benzodiazepines?

What Did My Patient Actually Take? An Overview of Benzodiazepine Results | Aegis Sciences Corporation Friday, December 20, 2019 Our series on interpreting unexpected results concludes with a discussion on the interpretation of benzodiazepine results from Aegis Sciences Corporation.

• Please note that the interpretation of benzodiazepine results differs when using presumptive vs.
• Definitive testing methods, and may differ among laboratories.
• The information provided here is intended to assist providers with deciphering benzodiazepine results from Aegis, which have undergone definitive testing by liquid chromatography/tandem mass spectrometry prior to reporting as positive.

Considerations for Interpreting Unexpected Results In the case of unexpected positive benzodiazepine results, consider the following drug exposures: Chlordiazepoxide (Librax®, Librium®), Clorazepate (Gen-xene®, Tranxene®), Diazepam (Valium®), Oxazepam, and/or Temazepam (Restoril®).

• Some commonly prescribed benzodiazepines have unique metabolites, which make identification more straightforward:
• Alprazolam (Xanax®): Metabolizes to alpha-hydroxyalprazolam; reported as Alprazolam Clonazepam (Klonopin®): Metabolizes to 7-aminoclonazepam; reported as Clonazepam Flurazepam: Metabolizes to 2-hydroxyethylflurazepam; reported as Flurazepam Lorazepam (Ativan®): Metabolizes to lorazepam glucuronide; reported as Lorazepam
• A patient taking alprazolam, clonazepam, flurazepam, or lorazepam will not test positive for benzodiazepine metabolites on an Aegis report.
• Opportunities for Exposure

Prescription: Benzodiazepines are controlled substances, and legitimate prescriptions would show up on the prescription drug monitoring program (PDMP) in most cases. Please note that chlordiazepoxide, when administered with clidinium (Librax®), is not a controlled substance in many jurisdictions and may not show up on the PDMP in these states.

• Procedural Administration: Abenzodiazepine may be administered as an anxiolytic or sedative prior to medical procedures.
• If the medication was directly administered to the patient by the treating provider, record of this may not be part of the patient’s PDMP report.
• A review of medical records may be necessary to determine the medications given to the patient prior to or during a procedure.

Hospitalization/Emergency Department Visit: Patients who arrive at the emergency room with a suspected poisoning or overdose may be given benzodiazepines depending on their presenting symptoms and the source of the toxicity. A benzodiazepine may also be given as an anxiolytic, pre-procedurally, or for treatment of a seizure.

If the patient reports a recent hospitalization or emergency department visit, follow-up with the hospital may be necessary to determine what medications were administered to the patient. Illicit Exposure: Sources of illicit exposure may include use of another person’s prescription drug, acquisition of counterfeit or other illicit drugs unknowingly laced with benzodiazepines, or exposure to illicitly manufactured benzodiazepines which may share metabolites with FDA-approved benzodiazepines.3 What medication is the patient prescribed? In many cases, the result interpretation may be clarified by correctly indicating the patient’s prescribed medications when ordering testing.

Any questions about how to list medications as prescribed on an Aegis laboratory requisition may be directed to the Aegis Client Services department at 1-800-533-7052. In general, the following guidance may be helpful:

Drug Prescribed	Drug to Mark as Prescribed	Expected Result 1,2
Alprazolam	Alprazolam	Positive for alprazolam and alpha-OH-alprazolam Parent drug may not be present in all results; only one marker is required for a positive result If parent drug is present in urine with no alpha-OH-alprazolam present, please consult the Aegis Clinical Team as multiple clinical factors may be pertinent to result interpretation, and this does not always indicate aberrant patient behavior
Clonazepam	Clonazepam	Positive for 7-aminoclonazepam
Diazepam	Benzodiazepine (Electronic Requisition) Diazepam (Paper Requisition)	Positive for Benzodiazepine Metabolites Nordiazepam, Temazepam, and/or Oxazepam may be present Only one marker is required for a positive result
Flurazepam	Flurazepam (Electronic Requisition)

ul>

Write in “Other” field

(Paper Requisition)

Positive for 2-hydroxyethylflurazepam

Lorazepam

Lorazepam

Positive for Lorazepam

Oxazepam

Benzodiazepine

(Electronic Requisition)

Oxazepam

(Paper Requisition)

Positive for Benzodiazepine Metabolites

• Only Oxazepam should be present
• Presence of other benzodiazepine markers may indicate ingestion of other benzodiazepines

1. Temazepam
2. Benzodiazepine
3. (Electronic Requisition)
4. Temazepam
5. (Paper Requisition)
6. Positive for Benzodiazepine Metabolites

• Only Temazepam and/or Oxazepam should be present
• Presence of other benzodiazepine markers may indicate ingestion of other benzodiazepines

When was the patient’s last dose? The period of detection for benzodiazepines varies greatly according to the specimen type utilized for testing and the patient’s dosing regimen. Benzodiazepines may be detected for a longer period of time in urine compared to oral fluid and blood.

In blood, especially, the period of detection is generally limited to very recent use. The detection time may be less in all specimen types in cases of as-needed dosing or ingestion of low doses. In settings of abuse or detoxification, the period of detection may be longer. Diazepam in particular has been noted to be detected longer in the urine of obese patients.4 Period of detection studies in toxicology are often limited, and special populations of patients are often excluded.

If there is a particular scenario involving unexpected results, the Aegis Clinical Team is happy to review available literature to examine possible causes of such results. Does the patient have altered gastrointestinal (GI) function or recent GI illness? Some patients have short-gut syndrome due to previous surgeries or GI disease or may have a history of gastric bypass surgery.

Providers may consider the possibility of reduced absorption of drug and potential impact on unexpected negative results in these patients. Vomiting and diarrhea can disrupt normal absorption and metabolism of medications and reduce excreted amounts to undetectable levels. Providers may also consider recent GI illness in the interpretation of unexpected negative results.

If evaluating urine results, is the sample dilute? Aegis provides special report comments to alert providers when the urine creatinine falls below 20 mg/dL. Urine samples with such a low creatinine level are less concentrated, and urine drug concentrations may fall below the reporting threshold in such samples.

Patients who drink a lot of water, consume caffeine, take diuretic medications, have disorders of antidiuretic hormone, or other physiologic disturbances affecting urinary concentration may produce less concentrated urine. Intentional dilution may occur either with intentional ingestion of copious amounts of water or by adding water to the urine sample from the restroom sink or toilet.

Such aberrant behavior should be considered in the context of the entire patient presentation with a provider using his or her clinical judgment to assess this possibility. Coloring the toilet water blue prior to sample collection and assessing the urine temperature within 4 minutes of collection (should be between 90°F and 100°F) are additional measures to check for sample tampering.5-6 Further information regarding specimen tampering is available in the Aegis Clinical Reference Guide at,

Click on the title “Specimen Validity Testing and Specimen Tampering” to download a copy of this chapter. Are there concerns with drug and sample stability such as improper storage or delays in shipment? If evaluating urine results, the sample pH may be an indicator of sample stability. Although the impact of urine pH would not likely be so significant to cause unexpected negative results, providers may consider that an elevated urine pH may be a natural physiologic response to regulate the body’s acid-base balance, or it may also be elevated if the urine was not stored properly prior to shipment.

In the case of improper storage, drug degradation contributing to unexpected negative results may be possible. Clonazepam in particular is more prone to stability issues. Losses of 7-aminoclonazepam in urine averaging 43% have been reported under refrigerated conditions at 2 months.7 A 76% drop in clonazepam concentration has occurred in an oral fluid specimen stored at room temperature overnight.8 Complete loss of clonazepam in oral fluid has occurred in 7 days at room temperature.9 In oral fluid, losses of 7-aminoclonazepam up to 20% and 33% have been observed at room and refrigerated temperatures, respectively, over a week.10 Providers may consider these known issues particularly when evaluating unexpected negative clonazepam results.

These stability issues along with as-needed dosing and/or low doses may further increase the likelihood of unexpected negative results. Further information regarding specimen stability is available in the Aegis Clinical Reference Guide at, Click on the title “Drug Stability and Toxicology Testing” to download a copy of this chapter.

Is the patient on dialysis? If testing a dialysis patient, testing prior to dialysis is recommended or at least on a non-dialysis day to reduce the possibility of unexpected negative results. Some dialysis patients are able to produce urine, but the urine produced may not be the result of normal filtration and excretion of drug and as such may not be clinically useful for drug compliance testing.

Point of Care Testing Considerations Some point-of-care testing (POCT) devices may result in a false positive for benzodiazepines in patients who are taking certain medications.6,11-17 Cross reactivity can occur with this type of testing among drugs with similar chemical structures.11 Non-benzodiazepine prescription, illicit, or over-the-counter drugs would not cause a false positive for benzodiazepines or benzodiazepine metabolites on Aegis definitive testing.

Please see below for a list of drugs which may cause a false positive for benzodiazepines on POCT.6,11-15 Please refer to the package insert that came with the POCT device being used or contact the manufacturer for more information regarding which drugs may cause false positive results as this information may differ among devices and manufacturers. False negative immunoassay results may also occur due to failure of the assay to react to drug-specific markers such as alpha-OH-alprazolam, 7-aminoclonazepam, 2-hydroxyethylflurazepam, and lorazepam glucuronide.6,11,12,16,18-21 At Aegis, we understand your concerns as you evaluate definitive drug testing results.

1. Unexpected benzodiazepine results may be indicative of noncompliance, drug misuse, or diversion, and we welcome your calls and e-mails for assistance in interpreting these results.
2. NOTICE: The information above is intended as a resource for health care providers.
3. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct.

References: 1. Baselt, RC. Disposition of toxic drugs and chemicals in man.11th ed. Seal Beach, CA: Biomedical Publications; 2017.2. Mandrioli R, Mercolini L, Raggi MA. Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab,2008;9(8):827-443.

• Moosmann B, Link LA, Auwarter V.
• Designer benzodiazepines: a new challenge.
• World Psychiatry.2015:14(2):248.4.
• Abernathy DR, Greenblatt DJ, Divoll M, Shader RI.
• Prolonged accumulation of diazepam in obesity.
• J Clin Pharmacol,1983;23:369-765.
• Cook JD, Caplan YH, LoDico CP, et al.
• The characterization of human urine for specimen validity determination in workplace drug testing: a review.

J Anal Toxicol.2000;24:579-88.6. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc.2008;83(1):66-76.7. Gonzales E, Ng G, Pesce A, et al. Stability of pain-related medications, metabolites, and illicit substances in urine.

Clin Chim Acta.2013:416:80-58. Hart BJ, Wilting J, de Gier JJ. The stability of benzodiazepines in saliva. Methods Find Exp Clin Pharmacol.1988;10(1):21-6.9. Kempf J, Wuske T, Schubert R, Weinmann W. Pre-analytical stability of selected benzodiazepines on a polymeric oral fluid sampling device. Forensic Sci Int.2009;186:81-510.

Lund HM, Øiestad El, Gjerde H, Christophersen AS. Drugs of abuse in oral fluid collected by two different sample kits—stability testing and validation sing ultra performance tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci.2011;3367-77.11.

Gourlay DL, Heit HA, Caplan YH. Urine drug testing in clinical practice: the art and science of patient care.6 th ed. Stamford, CT: PharmaCom Group, Inc.; 2015:1-32.12. Reisfield GM, Goldberger BA, Bertholf RL. ‘False-positive’ and ‘false-negative’ test results in clinical urine drug testing. Bioanalysis.2009;1(5):937-52.13.

Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Commonly prescribed medications and potential false-positive urine drug screens. Am J Health-Syst Pharm.2010;67:1344-50.14. Smith ML. Immunoassay. In: Levine B, ed. Principles of Forensic Toxicology.4 th ed.

Washington, D.C. AACC Press;2013:149-69.15. Blank A, Hellstern V, Shuster D, et al. Efavirenz treatment and false-positive results in benzodiazepine screening tests. Clin Infect Dis,2009;48(12):1787-9.16. Kirsh KL, Heit HA, Huskey A, et al. Trends in drug use from urine drug testing of addiction treatment clients.

J Opioid Manag,2015;11(1):61–8.17. Johnson-Davis KL, Sadler AJ, Genzen JR. A retrospective analysis of urine drugs of abuse immunoassay true positive rates at a national reference laboratory. J Anal Toxicol,2016;40:97-107.18. Mikel C, West R, Crews B, et al.

LC-MS/MS extends the range of drug analysis in pain patients. Ther Drug Monit.2009;31(6):746-8.19. Pesce A, Rosenthal M, West R, et al. An evaluation of the diagnostic accuracy of liwuid chromatography-tandem mass spectrometry versus immunoassay drug testing in pain patients. Pain Physician.2010;13(3):273-81.20.

Snyder ML, Fantz CR, Melanson S. Immunoassay-based drug tests are inadequately sensitive for medication compliance monitoring in patients treated for chronic pain. Pain Physician,2017;20:SE1-9.21. Mikel C, Pesce AJ, Rosenthal M, West C. Therapeutic monitoring of benzodiazepines in the management of pain: current limitations of point of care immunoassays suggest testing by mass spectrometry to assure accuracy and improve safety.

What would make you fail a drug test for Benzos?

Sertraline (Zoloft) is a selective serotonin reuptake inhibitor (SSRI). Sertraline can cause a positive result for the hallucinogen LSD on a urine drug test. It may also cause a positive result for benzodiazepines. Trazodone is an older antidepressant that’s not commonly used for depression anymore.

Why would I test negative for benzodiazepines?

6,7 This antibody has relatively low cross reactivity with clonazepam and lorazepam and is therefore less likely to be detected reliably. Another reason a benzodiazepine test may be falsely negative is that a dose may not be of a sufficient concentration to reach the detection threshold level in the urine.

What drugs show up in urine drug test?

Drugs of Abuse Home Use Test What do these tests do? These tests indicate if one or more prescription or illegal drugs are present in urine. These tests detect the presence of drugs such as marijuana, cocaine, opiates, methamphetamine, amphetamines, PCP, benzodiazepine, barbiturates, methadone, tricyclic antidepressants, ecstasy, and oxycodone.

1. The testing is done in two steps.
2. First, you do a quick at-home test.
3. Second, if the test suggests that drugs may be present, you send the sample to a laboratory for additional testing.
4. What are drugs of abuse? Drugs of abuse are illegal or prescription medicines (for example, Oxycodone or Valium) that are taken for a non-medical purpose.

Non-medical purposes for a prescription drug include taking the medication for longer than your doctor prescribed it for or for a purpose other than what the doctor prescribed it for. Medications are not drugs of abuse if they are taken according to your doctor’s instructions.

What type of test are these? They are qualitative tests – you find out if a particular drug may be in the urine, but not how much is present. When should you do these tests? You should use these tests when you think someone might be abusing prescription or illegal drugs. If you are worried about a specific drug, make sure to check the label to confirm that this test is designed to detect the drug you are looking for.

How accurate are these tests? The at-home testing part of this test is fairly sensitive to the presence of drugs in the urine. This means that if drugs are present, you will usually get a preliminary (or presumptive) positive test result. If you get a preliminary positive result, you should send the urine sample to the laboratory for a second test.

the way you did the testthe way you stored the test or urinewhat the person ate or drank before taking the testany other prescription or over-the-counter drugs the person may have taken before the test

Note that a result showing the presence of an amphetamine should be considered carefully, even when this result is confirmed in the laboratory testing. Some over-the-counter medications will produce the same test results as illegally-abused amphetamines.

1. Does a positive test mean that you found drugs of abuse? No.
2. Take no serious actions until you get the laboratory’s result.
3. Remember that many factors may cause a false positive result in the home test.
4. Remember that a positive test for a prescription drug does not mean that a person is abusing the drug, because there is no way for the test to indicate acceptable levels compared to abusive levels of prescribed drugs.

If the test results are negative, can you be sure that the person you tested did not abuse drugs? No. No drug test of this type is 100% accurate. There are several factors that can make the test results negative even though the person is abusing drugs.

1. First, you may have tested for the wrong drugs.
2. Or, you may not have tested the urine when it contained drugs.
3. It takes time for drugs to appear in the urine after a person takes them, and they do not stay in the urine indefinitely; you may have collected the urine too late or too soon.
4. It is also possible that the chemicals in the test went bad because they were stored incorrectly or they passed their expiration date.

If you get a negative test result, but still suspect that someone is abusing drugs, you can test again at a later time. Talk to your doctor if you need more help deciding what steps to take next. How soon after a person takes drugs, will they show up in a drug test? And how long after a person takes drugs, will they continue to show up in a drug test? The drug clearance rate tells how soon a person may have a positive test after taking a particular drug.

Drug	How soon after taking drug will there be a positive drug test?	How long after taking drug will there continue to be a positive drug test?
Marijuana/Pot	1-3 hours	1-7 days
Crack (Cocaine)	2-6 hours	2-3 days
Heroin (Opiates)	2-6 hours	1-3 days
Speed/Uppers(Amphetamine, methamphetamine)	4-6 hours	2-3 days
Angel Dust/PCP	4-6 hours	7-14 days
Ecstacy	2 to 7 hours	2 – 4 days
Benzodiazepine	2 -7 hours	1 – 4 days
Barbiturates	2 – 4 hours	1 – 3 weeks
Methadone	3 – 8 hours	1 – 3 days
Tricyclic Antidepressants	8 – 12 hours	2 – 7 days
Oxycodone	1 – 3 hours	1 – 2 days

How do you do a drugs of abuse test? These tests usually contain a sample collection cup, the drug test (it may be test strips, a test card, a test cassette, or other method for testing the urine), and an instruction leaflet or booklet. It is very important that the person doing the test reads and understands the instructions first, before even collecting the sample.

This is important because with most test kits, the result must be visually read within a certain number of minutes after the test is started. You collect urine in the sample collection cup and test it according to the instructions. If the test indicates the preliminary presence of one or more drugs, the sample should be sent to a laboratory where a more specific chemical test will be used order to obtain a final result.

Some home use kits have a shipping container and pre-addressed mailer in them. If you have questions about using these tests, or the results that you are getting, you should contact your healthcare provider. Useful Links: : Drugs of Abuse Home Use Test

Does diazepam test positive for benzo?

What do my test results mean? – Test results may vary depending on your age, gender, health history, and other things. Your test results may be different depending on the lab used. They may not mean you have a problem. Ask your healthcare provider what your test results mean for you.

A typical benzodiazepine urine test can find benzodiazepines or their break-down products, called metabolites. But this is a very complex test. A positive test result means that the test found the medicine’s metabolite in your urine at the time the urine sample was taken. The amount found is called the threshold concentration.

This means there was enough metabolite to measure. It does not mean the amount was enough to show you are actively using the medicine. The time it takes for a substance to show up in the urine varies by medicine. It can show up within minutes of taking the medicine, and it can last for days.

• The presence of benzodiazepines varies a lot by each medicine’s half-life.
• Half-life means the amount of time it takes for half of the medicine to be eliminated from the body.
• Diazepam, for example, can be found for weeks after the last dose.
• Although most benzodiazepines show up in standard urine tests, some don’t.

Alprazolam, clonazepam, temazepam, and triazolam may not be found in many of the common tests. Many benzodiazepine tests can find whether the medicine is present, but they can’t give the amount. A medicine called flumazenil may be used as an antidote to the sedative effects of benzodiazepines.

What is the detection of benzodiazepines?

Typical detection windows for benzodiazepines in the urine are 2 to 7 days, depending on the individual benzodiazepine drug used and other factors, such as time of last dose, drug half-life, route of administration, and individual differences in pharmacokinetics.

Can I take 2 diazepam 5mg at once?

Standard Valium Dosage – Understanding what constitutes a standard Valium dose regimen can better illustrate this point. Doctors generally recommend the drug should be used at dosages of 2-10 mg. This amount can be taken up to four times in a 24-hour time frame.

What are diazepam metabolites in urine?

Diazepam is metabolized to either nordiazepam by CYP 2C19 or temazepam by CYP3A4. Nordiazepam and temazepam are hydroxylated and demethylated to oxazepam. Oxazepam is then glucuronidated and excreted in the urine.

Do urine tests test for Benzos?

Specimen Type

Test ID	LAB367
EPIC ORDER	BENZODIAZEPINE, URINE QUAL
CPT Code(s)	80307
Group/Individual Test	Individual
Laboratory	Core Laboratory
Tube Station	Routine: 30 STAT: 888
Specimen	Routine:	10 mL Random Urine in Yellow Top Urine Tube (No Preservative/Additive); See important comments 10 mL Random urine in Sterile collection cup is acceptable if refrigerated.
Micro:	4 mL Random Urine in Yellow Top Urine Tube (No Preservative/Additive)
Stability	Room Temperature:	7 days
Refrigerated:	30 days
Frozen:	12 months
Availability	24 hrs/day
Turnaround Time	Routine: 2 hours STAT: 1 hour
Reference Range	Cutoff Value:	<200 ng/mL
Comments	Benzodiazepine metabolites may be detected up to 72 hours after ingestion depending upon the specific benzodiazepine. The urine benzodiazepine screening test detects the presence of the benzodiazepine/diazepam at a concentration of 200 ng/mL or greater. Other benzodiazepine are detected, call laboratory for information regarding a specific benzodiazepine. This method is unable to distinguish between specific benzodiazepines and should be used for screening. Confirmation testing should be considered for positive screens; ( See Benzodiazepines, Confirmation.) Note: These results are for medical purposes only. For additional information related to drug screening, refer to the Urine Toxicology Chart, Screen components may vary by lab location.

Reviewed by Christopher Parker on January 11, 2022 Note: Reference ranges provided on this web site are for guidance only, and may not reflect the most recent changes. Refer to laboratory reports for current reference data. UNC Hospitals McLendon Clinical Laboratories 101 Manning Drive Chapel Hill, NC 27514

What is a false negative on a urine drug test?

Interpreting Test Results – Many drugs are rapidly metabolized into active or inactive metabolites. Drug testing is dependent on detecting these metabolites. Opioids and benzodiazepines include multiple drugs with overlapping metabolic pathways, which can make interpretation of screening results difficult ( and ), False-positive results can occur from cross-reactivity of commonly used medications with the assay. This a particular concern with immunoassays. lists common medications that can cause false-positive results on urine drug testing. Negative results are particularly difficult to interpret, especially when a patient is receiving long-term opioid therapy and the physician expects a positive result.

True-negative results occur when a patient is not taking the medication as prescribed and there is no drug present in the urine sample, or when the drug is metabolized so rapidly that the metabolites are eliminated before they can be detected. False-negative results occur when a drug or metabolite is present at such low levels that it is not detected.

Confirmatory testing is essential to distinguish a true negative from a false negative. Contaminants can also interfere with the immunoassay’s ability to detect the presence of drugs. The use of heroin with concurrent prescription opioids is also a cause for concern. Although both substances will give a positive result for opioids, the presence of 6-monoacetylmorphine indicates heroin use. This metabolite has a short half-life, however, with a window of detection in urine of approximately two to eight hours.

What happens if you can’t pee for a drug test?

If I cannot provide sufficient urine during a drug test, is it a refusal? If you fail to provide a sufficient amount of urine when directed, and it has been determined, through a required medical evaluation, that there was no adequate medical explanation for the failure, it may be considered a refusal to test.

When you report for testing, you must make an attempt to provide a specimen. If you are unable to provide a sufficient amount of urine for a drug test, the collector must begin the “shy bladder” procedures. This procedure requires that you remain at the collection site. The collector must urge you to drink 40 ounces of fluid over a three-hour period until you provide a sufficient amount of urine or the three-hour time period has elapsed.

After three hours, if you did not provide a sufficient amount of urine, the collector must contact your employer’s Designated Employer Representative (DER) to advise him/her that you were not able to provide a specimen. After the DER consults with the company’s Medical Review Officer (MRO), you will be directed to obtain a medical evaluation within five days by a physician (or the MRO) who has expertise in the medical issues raised by your failure to provide a sufficient specimen.

If the MRO makes a determination that a medical condition precludes you from providing a sufficient amount of urine, the test may be cancelled, and it would not be considered a refusal. However, if the MRO determines there is no medical condition that precludes you from providing a sufficient urine sample, the collection will be deemed a refusal to submit.

The Department of Transportation’s Web site (http://www.dot.gov/odapc) includes an employee guide that may help you better understand your responsibilities for testing. If you have any further questions or need additional guidance that is more specific to your situation, please contact the FAA Drug Abatement Division at (202) 267-8442 or,

Can a urine test give a false negative?

Interpreting Test Results – Misinterpretation of UDS results may have adverse consequences for patients, including unwarranted loss of a job, potential criminal charges, loss of qualification from sporting events or rehabilitation programs, potentially improper medical treatment, or loss of trust from healthcare professionals.2,3 Patients who are required to receive random or recurrent UDS testing as part of rehabilitation programs; as a stipulation of employment; for health monitoring, such as for pain management or medication compliance; or for other reasons are at particularly high risk of negative consequences from misinterpreted UDS results.1,4 To decrease the likelihood of misinterpretation, pharmacists can help by identifying medications at high risk for causing false-negatives and false-positives and choosing medications less likely to cause these inaccuracies. Patients may purposefully attempt to hide positive screening results by adding contaminants to their urine that mask the presence of a drug, such as vinegar, soap, bleach, drain cleaner, eye drops, table salt, or ammonia.5 Additionally, commercial products with the active ingredients peroxide (peroxidase), glutaraldehyde, sodium or potassium nitrite, and pyridinium chlorochromate could be used.5 Changes in urine appearance, color, specific gravity, or pH may indicate the presence of a contaminant and should be checked.

1. Patients may also drink an excessive amount of water (2-4 qt) or use diuretics to purposefully dilute their urine and the urine drug concentration to decrease the chance of detection.5,6 Furthermore, false-negatives may also occur because the UDS is simply unable to detect the agent.
2. For example, UDS tests for benzodiazepines commonly result in false-negatives for agents that have poor cross-reactivity with the assay.7 Most assays for benzodiazepines detect their presence in the urine by testing for nordiazepam and oxazepam, the main metabolites of most benzodiazepines.2 Agents that follow a different metabolic pathway, such as triazolam, alprazolam, clonazepam, and lorazepam, have poor cross-reactivity with the assay due to the absence of these metabolites and thus frequently produce false-negative results.2,7 Therefore, to decrease the need for confirmatory testing, diazepam, oxazepam, and temazepam may be preferred.

Similarly, opiates can be at risk for false-negatives. Most immunoassay tests look for morphine, norcodeine, and codeine; thus morphine, heroin, and codeine can easily be detected. Hydrocodone and hydromorphone are metabolites of codeine and are rarely positive on immunoassay tests.

• Oxycodone, buprenorphine, and tramadol follow a separate metabolic pathway, and fentanyl may not be detected because it lacks metabolites.1,4 To minimize the need for confirmatory testing, consider using morphine or codeine in high-risk patients.
• For patients being treated for attention-deficit/hyperactivity disorder (ADHD), UDS testing may also be recommended.

Immunoassays test for amphetamines; thus, amphetamine, dextroamphetamine, and lisdexamfetamine products should return positive results for compliance testing if taken in the last 2 to 3 days. Illicit methamphetamine will also show positive within the amphetamine immunoassay test.

However, methylphenidate products do not cross-react with amphetamines and will commonly produce negative results, 8 although a false-positive result with methylphenidate has been seen in one pediatric case report.1-2,8 If methylphenidate products are used, a GC-MS test should be routinely administered.

False-Positives: In addition to false-negatives, pharmacists need to consider the potential for false-positive UDS results and be aware of medications that may cause false-positives. TABLE 2 summarizes many medications that have been reported to cause false-positive results with common substances of abuse or tricyclic antidepressants (TCAs).1-4 False-positives can occur when a medication has a cross-reactivity with the immunoassay, often due to a similarity in the structure of the parent medication or one of its metabolites to the tested drug.2 The occurrence of false-positives is mostly affected by the type of immunoassay used and by the particular agent being tested.2 When selecting therapeutic agents for high-risk patients, pharmacists should consider minimizing the use of drugs known to cause false-positive results, if possible. The selection of an appropriate therapeutic agent for a patient depends on numerous factors, such as the effectiveness and adverse-effect profile of the drug; therefore, minimizing the use of medications shown to cause false-positives must be weighed against clinical judgment in product selection.

What is the false negative rate for urinalysis?

Urinalysis in Acute Care of Adults: Pitfalls in Testing and Interpreting Results Received 2014 Mar 4; Accepted 2014 Apr 10. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact [email protected].  Rapid urine tests for infection (urinalysis, dipstick) have low up-front costs. However, many false positives occur, with important downstream consequences, including unnecessary antibiotics. We studied indications, collection technique, and results of urinalyses in acute care.  This research was a prospective observational study of a convenience sample of emergency department (ED) patients who had urinalysis performed between June 1, 2012 and February 15, 2013 at an urban teaching hospital. Analyses were conducted via t tests, χ 2 tests, and multivariable logistic regression.  Of 195 cases included in the study, the median age was 56 and 70% of participants were female. There were specific symptoms or signs of urinary tract infection (UTI) in 74 cases (38%; 95% confidence interval, 31%–45%), nonspecific symptoms or signs in 83 cases (43%; 95% CI, 36%–50%), and no symptoms or signs of UTI in 38 cases (19%; 95% CI, 14%–25%). The median age was 51 (specific symptoms), 58 (nonspecific symptoms), and 61 (no symptoms), respectively ( P =,005). Of 137 patients who produced the specimen without assistance, 78 (57%; 95% CI, 48%–65%) received no instructions on urine collection. Correct midstream clean-catch technique was used in 8 of 137 cases (6%). Presence of symptoms or signs was not associated with a new antibiotic prescription, but positive urinalysis (OR, 4.9; 95% CI, 1.7–14) and positive urine culture (OR, 3.6; 95% CI, 1.1–12) were. Of 36 patients receiving antibiotics, 10 (28%; 95% CI, 13%–43%) had no symptoms or nonspecific symptoms.  In this sample at an urban teaching hospital ED, urine testing was not driven by symptoms. Improving practice may lower costs, improve efficiency of care, decrease unnecessary data that can distract providers and impair patient safety, decrease misdiagnosis, and decrease unnecessary antibiotics. Keywords: antibiotic stewardship, asymptomatic bacteriuria, urinalysis, urine culture, urinary tract infection Unnecessary antibiotics cause resistance, Clostridium difficile diarrhea, side-effects, and allergic reactions, Inappropriate treatment of asymptomatic bacteriuria has been a target of quality improvement efforts, including efforts to promulgate a national quality improvement measure from the Infectious Diseases Society of America, The problem of inappropriate treatment of asymptomatic bacteriuria has been studied most in long-term care facilities but less in acute-care settings, such as the emergency department (ED), There are 130 million US ED visits each year, accounting for 11% of ambulatory healthcare visits and half of hospital admissions, Urinary tract infection (UTI) is the 4th most common diagnosis among women aged ≥65 years, The ED has been identified as an important site for antibiotic stewardship, but these considerations apply to all acute-care settings that perform urine tests, Among the millions of acute-care diagnoses of UTI, it is difficult to know how many are correct and how many courses of antibiotics are justified. One study concluded that 27% of ED patients with positive urine cultures had asymptomatic bacteriuria not UTI, Another study found that the prevalence of positive culture among elderly ED patients with no symptoms was similar to that among those with vague symptoms such as delirium, for which urinalysis is frequently done, We report data from a prospective observational study of ED patients undergoing urinalysis. We describe symptoms and signs, sampling technique, test characteristics, and antibiotic use. Our objective is to look beneath the surface of this deceptively simple test, to identify the complexities that impair quality practice, and to provide a framework that can resolve these complexities to benefit future practice and research. We conducted a prospective observational study in the ED of an urban teaching hospital between June 1, 2012 and February 15, 2013, enrolling a convenience sample of ED patients who had urinalysis performed as part of usual care. Trained research assistants identified cases by monitoring our electronic tracking system, which displays an icon when urine test results are available. This study was reviewed by our institutional review board and was exempted from review because it was determined to have the legal or ethical status of “quality improvement activity” rather than “human subjects research.” Nevertheless, each patient who was interviewed gave verbal consent to participate. Using structured data forms, data were collected by interview of patients and providers. Participants were asked to describe sample collection step-by-step. Females were shown an anatomically correct drawing of the vulva to determine specifically what actions they took in preparing to give the specimen. We define correct midstream clean-catch technique as obtainment of a midstream specimen after wiping the urethral opening with an antiseptic towelette, with separation of labia and wiping from front to back by women, or retraction of foreskin by uncircumcised men. We define a urinalysis as positive if it contains nitrites, leukocyte esterase, bacteria, or >10 white blood cells per high-power field. We define positive urine culture as >100 000 colony-forming units of a single species (voided) or >100 colony-forming units of a single species (catheterized), We define UTI as urethritis, cystitis, or pyelonephritis. However, the simplicity of this definition belies some important problems with construct validity. The concept “UTI” has high validity when applied to a healthy young female with no sexual exposures who presents with acute dysuria, pyuria, and bacteriuria on urinalysis, and a positive urine culture. Construct validity is much less clear in the case of an 80-year-old woman with dementia who presents with a slight decline in functional status and happens to have pyuria and a positive culture. Yet both of these patients may receive antibiotics “for UTI” if seen in an acute-care setting. Therefore, we classify patients with positive urine cultures into 3 groups: (1) those with specific symptoms of UTI, (2) those with vague symptoms that are traditionally associated with UTI, and (3) those with no symptoms (Table ). Symptoms of Urinary Tract Infection a

UTI Symptoms/Signs Present Testing for UTI Indicated	UTI Symptoms/Signs Nonspecific Indication for Testing for UTI Ambiguous	UTI Symptoms/Signs Absent Testing for UTI Not Indicated
Any of the following symptoms or signs: Dysuria Urgency Frequency Flank pain Hematuria Costovertebral angle tenderness on percussion Sepsis with no other source Acute urinary retention Acute nephrolithiasis Obstruction of urinary catheter	Any of the following symptoms or signs: Unexplained acutely altered mental status Fever with no other explanation Rigors with no other explanation	All other patients: For example, urine testing is not indicated “just because the patient is being admitted” or “just because he fell.”

We report descriptive results as percentages and 95% confidence intervals (CIs) and P values via χ 2 testing. We used multivariable logistic regression to assess predictors of use of antibiotics, with the following independent variables: urinalysis results, urine culture results, and symptoms.

Characteristic	n (% of 195)
Age (median, interquartile range)	56 (40–70)
Female sex	137 (70)
Disposition
Home	106 (54)
Floor	79 (41)
Intensive care unit	6 (3)
Transfer	4 (2)
Long-term care facility resident	10 (5)
Symptoms of urinary tract infection
Specific	74 (38)
Nonspecific	83 (43)
None	38 (19)
Provider order for the urinalysis?	181 (93)
EM attending or PGY3+ EM resident	40 (21)
PGY1 or 2 EM resident or non-EM resident	55 (28)
Physician Assistant	86 (48)
No order	14 (7)
Collection technique
Voided	160 (82)
Catheterized	35 (18)
Among 137 unassisted voided specimens, how many received instructions?	78 (57)
Urine culture ordered	82 (42)
Urine culture done	83 (43)
Urine culture positive (% of cultures done)	21 (25)
Main clinical diagnosis for visit
Was main diagnosis infectious?	43 (22)
Antibiotic given in emergency department?	60 (31)

There were specific symptoms or signs of UTI in 38% (95% CI, 31%–45%), nonspecific in 43% (95% CI, 36%–50%), and none in 19% (95% CI, 14%–25%). Median ages were 51, 58, and 61, respectively ( P =,005). This result indicates that urine testing is done for less specific reasons among older patients. Symptom category did not vary by sex ( P =,18). However, sex was an effect modifier of the relationship of age to indication. Among women, median ages by indication category were 38 (specific), 58 (nonspecific), and 58 (none), respectively ( P <,001); however, among men, there was no significant age variation among the 3 indication groups, with median ages of 67, 61, and 68, respectively ( P =,30). This finding reveals more specific indications for testing among young women, relative to older women and men. Of the 195 subjects, there was no order for the urinalysis in 7% of cases (95% CI, 3.5%–11%). As a reminder, our site has no point-of-care testing. A higher rate of tests without orders would be expected at sites with point-of-care testing, because point-of-care testing does not require involvement of a central laboratory. Urine specimens were voided in 82% of cases and collected via catheterization in the remainder. In-person interviews revealed that, of 137 patients who produced the specimen without assistance, 78 (57%; 95% CI, 48%–65%) received no instructions from ED staff on urine collection. Results were similar for males (51%) and females (59%) and did not vary by age ( P =,77). Among participants producing a voided specimen without assistance, correct midstream clean-catch technique was used in 8 of 137 cases (6%). Urinalysis results were positive in 76 cases (39%; 95% CI, 32%–46%). Of the 195 subjects, urine culture was sent in addition to urinalysis in 83 (43%; 95% CI, 36%–50%). Urine culture was sent in 59% of subjects with positive urinalysis, versus 32% of subjects with negative urinalysis ( P <,001). Table summarizes the test characteristics of urinalysis as a proxy for urine culture. The sensitivity of urinalysis as a proxy for culture was 81% (false-negative rate, 19%) and the specificity was 54% (false-positive rate, 46%). More importantly, this result describes the accuracy of urinalysis as a proxy for a positive urine culture, not as a predictor of UTI. This distinction is important because UTI is often not present even when the culture is positive, due to contaminated specimens and asymptomatic bacteriuria, If there were a truly accurate test for bona fide UTI, the test characteristics of urinalysis as a proxy for that test would be worse. Test Characteristics of Urinalysis As a Proxy for Urine Culture Among Patients With Urinalysis and Urine Culture Sent During Routine Care a

Urinalysis Result	Urine Culture Result
Abnormal	Normal
Positive for infection	17	28
Negative for infection	4	34
Results (Test characteristics )
Sensitivity: 81% (64%–98%)
Specificity: 54% (42%–67%)
Negative predictive value: 89% (80%–99%)
Positive predictive value: 38% (24%–52%)
Likelihood ratio negative 0.35 (0.03–0.67)
Likelihood ratio positive 1.8 (1.2–2.4)

We also analyzed the sensitivity and specificity of urinalysis as a proxy for urine culture by symptom category. These results are presented for descriptive purposes only, because the study was not powered to detect differences in test categories among these small subsets of patients, precluding meaningful statistical comparison among these groups. Among patients with specific symptoms of UTI, sensitivity of urinalysis for urine culture was 92% and specificity was 48%. Among those with nonspecific symptoms, sensitivity was 57% and specificity was 58%. Among those with no symptoms of UTI, sensitivity was 24% and specificity was 76%. Of the 60, 24 received the antibiotics for a non-UTI indication, while 36 received antibiotics with no explanation other than suspected UTI. In this group of 36, symptoms were associated with the decision to use antibiotics: antibiotics were given to 3% of those with no UTI symptoms, 13% of those with nonspecific symptoms, and 40% of those with specific UTI symptoms ( P for trend <.001). However, to control for how urinalysis results influence decision-making irrespective of symptoms, we fit a multivariable model with antibiotic use as the dependent variable and the following predictors: positive urinalysis, positive urine culture, indication (specific, nonspecific, none ). In this controlled analysis, presence of symptoms and signs was not associated with antibiotic use, but positive urinalysis (OR, 4.9; 95% CI, 1.7–14) and positive urine culture (OR, 3.6; 95% CI, 1.1–12) were. Despite low barriers and low up-front cost, rapid urine testing for infection is complex. When rapid urine tests are done without appropriate indications and collection methods, downstream consequences may include misdiagnosis and unnecessary antibiotics. To clarify the complexities of urine testing in the acute-care setting, we studied a convenience sample of adult ED patients who had urinalysis. Our results suggest that testing is not driven by symptoms and that rapid test results, rather than symptoms, drive antibiotic utilization. To put our results in a context that may be helpful in planning future work, we present a framework that dissects the complexities underlying this deceptively simple process (Figure ). Step 1 addresses symptoms. When vague symptoms such as decreased functional status are present, there is no good way to differentiate UTI from coincidental asymptomatic bacteriuria, which is present in up to half of elderly female residents of long-term care facilities, These patients risk not only exposure to unnecessary antibiotics, but they also risk having the true diagnosis missed due to the cognitive error known as "premature closure." Older adults bear the brunt of these risks, because the prevalence of asymptomatic bacteriuria increases with age, as does the physical difficulty of correctly producing a midstream clean-catch specimen. In the present sample, just over one third of urinalyses were done without specific symptoms, and urinalysis was done without specific symptoms more commonly. Step 2 addresses which patients with no UTI symptoms should have testing for UTI. There is broad consensus that pregnant women and patients about to undergo urologic surgery should have their urine tested and sterilized, The Infectious Diseases Society of America, the Centers for Disease Control and Prevention, and other bodies offer strong guidance that no other patients should be treated for asymptomatic bacteriuria, However, in other areas, the relevance of these recommendations is questioned. For example, most orthopedic surgeons require testing for UTI before open reduction and internal fixation procedures, based on expert opinion, low-quality and conflicting evidence, and despite the fact that these patients will, in any case, receive a large dose of a cephalosporin before the skin incision, Likewise, although it may not be recommended in any credible text, many clinicians believe that all patients being admitted to the hospital should have a urinalysis and that positive results should lead to antibiotic treatment, regardless of symptoms. Step 3, an order for urine testing is a domain particularly relevant to the acute-care setting. Nurses and nurses' aides are efficient when they "hold" samples in anticipation of prescribers′ orders, but they communicate with the responsible prescriber before initiating testing. For Step 4, although special collection technique may not be required for accurate urine culture, it is quite important for accurate rapid testing (urinalysis or dipstick), Patients who are elderly, acutely or chronically ill, or disabled may have difficulty understanding or performing the maneuvers necessary for correct specimen collection, Two assistants may be required to obtain noncontaminated urine in this population. One study reported a 57% false-positive rate for urine cultures collected by midstream clean-catch in elderly hospitalized women, Busy clinicians may not understand the importance of collection technique nor take the time to provide appropriate instructions. Indeed, in our sample, correct midstream clean-catch technique was used in <5% of cases. Evidence suggests that good instructions do improve technique, although we had so few examples of correct technique that statistical comparison was not possible, Step 5 relates to interpretation of rapid urine test results. Prior studies have found a false-negative rate for rapid urine tests of approximately 20%, similar to our observed false-negative rate of 19%. Positive results are even more fraught, because of the following: (1) poor collection technique will produce a falsely positive specimen; (2) pyuria is a normal finding in the setting of asymptomatic bacteriuria ; (3) pyuria is a normal finding in the setting of acute nephrolithiasis ; and (4) positive nitrite is a specific indicator of the presence of bacteriuria but cannot differentiate UTI from poor collection technique or asymptomatic bacteriuria. As seen in the present data, the accuracy of urinalysis as an indicator of a positive urine culture is quite poor; we observed a sensitivity of 81% and a specificity of 54%. Urinalysis as an indicator of UTI is even poorer, because many patients with positive cultures do not have infections but rather have asymptomatic bacteriuria. This problem increases with age and debility, along with the prevalence of asymptomatic bacteriuria, Step 6 addresses therapy. Our analysis suggests that use of antibiotics was determined by tests results, not patients' symptoms. In Step 7, the decision is made whether to obtain a urine culture. In Step 8, the results of the urine culture are obtained and interpreted. In adults residing in long-term care facilities, great progress has been made in discouraging antibiotic use in the absence of relevant symptoms, In the acute-care setting, the first step should be judicious test ordering. However, inevitably, some adults with vague or absent symptoms will be found to have pyuria. In this case, the crucial distinction might be patient stability. Patients with sepsis should be treated aggressively. However, for patients who are stable, the best approach may be observation with mindfulness of the prevalence of asymptomatic bacteriuria. Improving practice in this area requires education. The most important piece of information is the high prevalence of asymptomatic bacteriuria among the elderly, especially elderly female residents of long-term care facilities. demonstrates educational materials that have been used in seminars around Massachusetts. Educational Tools for Improving the Accuracy of Urine Testing. Developed by the Massachusetts Infection Prevention Partnership, which includes the Massachusetts Coalition for the Prevention of Medical Errors, Massachusetts Department of Public Health, and Massachusetts Senior Care Association, with its clinical advisors: Ruth Kandel MD, Director Infection Control, Hebrew Senior Life; Daniel Pallin MD, MPH, Director of Research, Brigham & Women's Hospital Department of Emergency Medicine; and Shira Doron MD, Antimicrobial Steward & Associate Hospital Epidemiologist, Tufts Medical Center. Used with permission. The data reported in this paper were from a convenience sample, and thus results cannot be presumed representative of all patients. As discussed above, our center has no point-of-care testing; centers with point-of-care testing probably have more frequent testing without orders and worse test performance, due to further separation of symptoms and testing. It would be valuable to repeat this study in a multicenter design, with comprehensive sampling, and include centers with point-of-care urine dipstick testing. Urinalysis and urine dipstick tests for infection are easy to obtain and inexpensive initially, but their results are complex to interpret and can have important downstream consequences. In this sample at an urban teaching hospital ED, urine testing was not driven by symptoms. Some approaches to improving practice include the following. Nurses and aides should communicate with prescribers rather than initiate tests, and, when communication is not immediately possible, they should "collect and hold" rather than perform tests. Appropriate collection techniques should be emphasized. Prescribers should order urine testing only with specific justification, and they should be mindful of the high prevalence of asymptomatic bacteriuria as they decide whether to order tests and how to interpret their results. Watchful waiting and attention to differential diagnosis are important in the setting of positive results, due to poor test specificity. Improving practice in this area may lower costs, improve efficiency of care, decrease unnecessary data that can distract providers, decrease misdiagnosis, and decrease unnecessary antibiotics. Financial support. This work was supported by a Jahnigen Career Development Award funded by grants from John A. Hartford Foundation and the Atlantic Philanthropies (to J.D.S.). Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.1. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis.2005; 40 :643–54.2. Bartlett JG. A call to arms: the imperative for antimicrobial stewardship. Clin Infect Dis.2011; 53 (Suppl 1):S4–7.3. Gross PA, Patel B. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria. Clin Infect Dis.2007; 45 :1335–7.4. Zabarsky TF, Sethi AK, Donskey CJ. Sustained reduction in inappropriate treatment of asymptomatic bacteriuria in a long-term care facility through an educational intervention. Am J Infect Control.2008; 36 :476–80.5. Linares LA, Thornton DJ, Strymish J, et al. Electronic memorandum decreases unnecessary antimicrobial use for asymptomatic bacteriuria and culture-negative pyuria. Infect Control Hosp Epidemiol.2011; 32 :644–8.6. Loeb M, Brazil K, Lohfeld L, et al. Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes: cluster randomised controlled trial. BMJ.2005; 331 :669.7. Samore MH, Bateman K, Alder SC, et al. Clinical decision support and appropriateness of antimicrobial prescribing: a randomized trial. JAMA.2005; 294 :2305–14.8. Gordon LB, Waxman MJ, Ragsdale L, et al. Overtreatment of presumed urinary tract infection in older women presenting to the emergency department. J Am Geriatr Soc.2013; 61 :788–92.9. May L, Cosgrove S, L'Archeveque M, et al. A call to action for antimicrobial stewardship in the emergency department: approaches and strategies. Ann Emerg Med.2013; 62 :69–77.e2.10. Khawcharoenporn T, Vasoo S, Ward E, et al. Abnormal urinalysis finding triggered antibiotic prescription for asymptomatic bacteriuria in the ED. Am J Emerg Med.2011; 0 :828–30.11. Ducharme J, Neilson S, Ginn JL. Can urine cultures and reagent test strips be used to diagnose urinary tract infection in elderly emergency department patients without focal urinary symptoms? CJEM.2007; 9 :87–92.12. Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare Safety Network (NHSN) report, data summary for 2009, device-associated module. Am J Infect Control.2011; 39 :349–67.13. Ollivere BJ, Ellahee N, Logan K, et al. Asymptomatic urinary tract colonisation predisposes to superficial wound infection in elective orthopaedic surgery. Int Orthop.2009; 33 :847–50.14. Glynn MK, Sheehan JM. The significance of asymptomatic bacteriuria in patients undergoing hip/knee arthroplasty. Clin Orthop Relat Res.1984; 0 :151–4.15. Canale ST, Beaty JH. Campbell's Operative Orthopaedics. Philadelphia, PA, USA: Elsevier/Mosby; 2012.16. Das RN, Chandrashekhar TS, Joshi HS, et al. Frequency and susceptibility profile of pathogens causing urinary tract infections at a tertiary care hospital in western Nepal. Singapore Med J.2006; 47 :281–5.17. Fisher LA, Johnson TS, Porter D, et al. Collection of a clean voided urine specimen: a comparison among spoken, written, and computer-based instructions. Am J Public Health.1977; 67 :640–4.18. Kaye D. Urinary tract infections in the elderly. Bull NY Acad Med.1980; 56 :209–20.19. Goldsmith BM, Campos JM. 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What causes false negative urinalysis?

Discussion – The study confirmed that discrepancies do appear despite the proper instructions given to patients regarding urine collection procedure. Numerous factors can affect the urine test (diet, exercise, hydration, medication), and patient training is needed. Sometimes despite proper training, some patients are not compliant (e.g., not declaring or not knowing about antibiotic use). Regarding this issue, we discuss why two subjects included in the study, although they were instructed regarding correct sample collection, did not know that the drugs they were using were antibiotics (cephalosporin). We did not exclude these two patients as they initially met the inclusion criteria and we wanted to emphasize this possibility of this type of discordance. Some patients, especially in during the cold and flu season, consume large amounts of vitamin C in the form of dietary supplements or in the form of foods and beverages containing vitamin C having a preservative and antioxidant effect. Examination of ascorbic acid interference has shown that the intensity of interference differs between dipsticks. Ascorbic acid interferes with glucose, hemoglobin, nitrite, and bilirubin at different concentrations causing false-negative results ( 8, 9 ). The specificity of red blood cell (RBC) testing can be limited, providing false-positive results and this aspect should be taken into account in the diagnosis of hematuria. In alkaline urine (pH>7.0) or diluted urine (density <1.010), RBCs can be lysed with hemoglobin release ( 3, 10 ). Strip testing of RBCs is influenced by ascorbic acid and gentisic acid (found in certain plants or drugs) ( 9 ). Hemoglobinuria, myoglobinuria, menstrual blood, concentrated urine, and strenuous exercise can cause a false-positive result on a dipstick test ( 4 ). A pH<5.1 and increased urinary density may result in false-negative reactions on the strip ( 4 ). Strong oxidizing agents, soaps, detergents, sodium hypochlorite, hydrogen peroxide directly oxidize chromogen and produce a reaction in the absence of hemoglobin, giving a false-positive result. In addition, microbial peroxidase produced by certain bacteria such as Escherichia coli can catalyze the reaction in the absence of hemoglobin peroxidase with false-positive results. Thus, dipstick hematuria must be confirmed by microscopic examination to rule out false-positive and false-negative results ( 2 ). Many of these discrepancies arise because patients presenting to the physician with symptoms of kidney disease, especially urinary tract infections, are treated with antibiotics before they perform a urine test. Leukocytes are particularly sensitive in hypotonic urine (density 7.0), being lysed ( 11 ). In the presence of bacteriuria, high temperature preservation and inappropriate centrifugation, leukocytes can also be lysed ( 4 ). False-negative results may occur when the elevated leukocyte count in urine is due to lymphocytes; the test is negative on the strip but positive for microscopic examination. Also, the presence of substances that reduce the sensitivity of the reaction to leukocyte esterase (glucose in urine >3 g/dl and proteins >500 mg/dl, ketone bodies) or strong oxidizing agents, and antibiotics such as gentamicin, nitrofurantion or tetracycline can give false results. The leukocyte esterase test provide false-positive reactions in case of the use of strong oxidizing agents or colored urine (bilirubinuria). A source of confusion can be the contamination of urine with vaginal mucus or secretion and also the use of certain drugs (nitrofurantion, clavulanic acid, meropenem and imipenem) ( 4, 12 ). Detection of nitrites can be reduced, resulting in false-negative results due to antibiotic therapy that inhibits the conversion of nitrates to nitrites as well as the presence of ascorbic acid, pH<6.0 and increased urinary density. Non-nitrate-reducing organisms also may cause false-negative results, and patients who consume a low-nitrate diet may have false-negative results ( 5 ). Incorrect sample collection may be associated with contamination. According to Pernille et al the main contaminants in first-void urine samples were Enterococcus spp., which contributes to the majority of false-positives results ( 13 ). Inappropriate handling and preservation of the urine sample can cause bacterial proliferation and nitrite formation in vitro ( 3 ). A negative test for nitrites does not exclude urinary infection, and a positive result for nitrite should indicate bacteriological cultures ( 14 ). Despite the discrepancies mentioned above, we obtained very good sensitivity and specificity for leukocytes, nitrites and RBCs for dipstick analysis when compared with the microscopic examination of urine sediment, making this test appropriate for urine analysis. According to Miler and Nikolac ( 15 ), there is no risk for the patients to exclude a microscopic exam, when dipstick testing is negative. This approach is also time saving ( 15 ). Bataille et al ( 16 ) showed that urinary dipstick qualifies as a better screening test for hematuria than urine microscopy analysis or flow cytometry, making dipstick urinalysis a good surrogate for urine microscopy. One important utility of dipstick testing is to indicate a possible urinary infection. A positive sample (nitrates, leukocyte esterase) is then sent for urine culture (the gold standard). The question that arises is if the test is good enough for screening purposes. In early phases of uncomplicated urinary tract infections, when low bacterial counts are typical, both leukocyte esterase and nitrites may be undetectable. Our research has some limitations. The samples were collected in a private laboratory and the numbers could be increased. In addition, the population who presented at the laboratory was variable in age and associated pathology. Similar studies have been commonly performed in hospitals in certain departments, in certain pathologies or age groups. One study assessed the accuracy of urine dipstick to predict urinary tract infections in an emergency department ( 17 ), and the sensitivity calculated for combined nitrite and leukocyte esterase test was 94% and the predictive value of nitrite and leukocyte esterase together for a negative urine culture was 95%. Another study showed that positive nitrate is the best indicator of a positive culture with a specificity of 99.3% but had a negative likelihood ratio of 0.7( 18 ). In a meta-analysis, Devillé et al ( 19 ) evaluated the accuracy of the urine dipstick test to rule out infections. The analysis of included studies showed high accuracy of nitrites in pregnant women and elderly individuals; PPV ≥80% in elderly and in family medicine. The highest sensitivity was reported in studies carried out in family medicine (90%). Of course, the urine culture is the gold standard with which to diagnose urinary infection. Knowing these discordant results, the laboratories must ensure that they take the necessary steps to correct them. The fact that we collected samples from the general population, regardless of age and associated pathology, brings value to our study, and our results may be useful to other laboratories. Despite proper training, some patients are not compliant with the urine collection procedure and this is an important pre-analytical source for false-negative or false-positive results. In conclusion, we identified a small percentage (1.92%) of inconsistencies between urinalysis and microscopic examination and our results confirm that dipstick urinalysis is an appropriate test.