UTI – Pearls and Pitfalls in Urine Testing

Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Case:

A 32-year-old female presents with cloudy and smelly urine, and she is concerned she may have a UTI. She denies dysuria, hesitancy, frequency, abdominal/flank pain, fevers, nausea/vomiting, and discharge. She had a UTI 5 years prior that presented with dysuria and frequency. Her VS are normal, and she displays no abdominal tenderness. Your nurse in triage already obtained a urine dipstick, which shows 2 WBCs, negative nitrites, trace LE, normal pH, and < 5 squamous cells.

Do you treat for UTI? Do you need to send a urine culture?

A prior EM@3AM post evaluated the basics of urinalysis and dipstick.  This post will evaluate pitfalls in urinalysis/dipstick in diagnosis of UTI and several populations where urine testing can present several challenges.

Background:

UTI is a common disease managed in the ED, classified by location and the presence of functional/anatomic abnormalities (upper vs. lower, simple vs. complicated).^1-7 The most common pathogen includes E. coli, followed by Staphylococcus saprophyticus.^1-5

Though history and physical exam are not 100% reliable, patients most commonly present with dysuria, urinary frequency, and urinary urgency. However, no specific history or physical examination finding can rule in or out UTI. Urinary frequency possesses a specificity of 60%, urgency 78-88%, dysuria 52-58%, and fever 69-91%.^3,6,8,9  A combination of dysuria and frequency with the absence of vaginal discharge and irritation yields a +LR over 24, with greater than 96% probability of UTI.^9,10 Overall, UTI is a clinical diagnosis.^2,3,10 This is an important point to keep in mind when evaluating the urinalysis.

Just as discussed in the prior EM@3AM post on urine testing, urinalysis and dipstick testing in combination with history and exam are the major means of diagnosis. Urine is normally sterile, and testing most commonly includes clean-catch midstream sample. Once urine is collected, it should be analyzed as soon as possible (delay may result in unreliable findings). If it cannot be analyzed quickly, the sample should be refrigerated.^11-13

Now, on to the pitfalls…

Pitfalls:

#1 – Assuming urine that is cloudy or smells is diagnostic for UTI

Urine color and odor should not be used to diagnose UTI. Change in urine color or clarity from the patient’s baseline can be due to diet change or the presence of urinary crystals. Urine odor is primarily related to serum and urine urea and hydration status, and foul-smelling urine is not related to the presence of UTI.^10-14-16

#2 – Positive WBC or LE is diagnostic for UTI

Leukocyte esterase positive testing displays sensitivity over 80% and specificity of 98% for pyuria.^9,10,17-19 However, the presence of WBC in urine is not diagnostic of UTI, as WBCs may be present with dehydration, oliguria, and anuria.^17,20 Sterile pyuria may occur in contaminated samples, nephritis, urolithiasis, tumors, intraabdominal disease such as appendicitis, and atypical organisms.^10,17,20 If a cutoff of > 3 cells/hpf is used alone for diagnosis, overtreatment occurs in 44% of patients.¹⁸ The majority of symptomatic UTIs display over 10 WBC/microL.¹⁰ Hematuria may also result in a false positive result.^17,20 Unfortunately, the test may be falsely negative in patients with neutropenia or leukopenia.^17,20 As we will discuss later, symptoms should be used in conjunction with testing.

#3 – Positive nitrites is diagnostic for UTI

Positive nitrite testing is highly specific for gram-negative bacteriuria (such as E. coli). Similar to LE or WBC in the urine, clinical symptoms should be utilized with testing.^3,10,17,20  If negative, this does not rule out UTI.^2,3,10 Nitrite testing requires a significant of dwell time within the bladder for the conversion of nitrate to nitrite, and other organisms may not have the enzyme necessary for positive testing.^17,20

A negative LE and nitrite test may be able to rule out UTI, with a sensitivity of 94%.²¹ A patient with urinary symptoms but negative LE and nitrite requires evaluation for other conditions.^2,3 Positive LE and nitrite together demonstrate specificities over 93% for UTI, but poor sensitivity at 48% in nursing home patients.²²

#4 – The presence of squamous cells in the sample means you cannot interpret the test accurately

Traditionally, less than 5 squamous cells per low powered field (lpf) is considered a relatively clean urine sample, with recommendations to repeat testing if over 5 SECs/lpf are found.^9,10,19 Unfortunately, SECs do not reliably suggest urine contamination. One study suggests SECs do not accurately predict contamination, but < 8 SECs/lpf has greater ability to predict bacteriuria.²³ LE and nitrite testing performs similarly despite the SEC count, and no specific threshold of SECs can predict a contaminated specimen.²³

#5 – Urine cultures should be obtained for every patient with diagnosed UTI

Urine testing is a component of almost every ED shift, and urine cultures are considered the definitive diagnostic modality for UTI, with ≥ 10⁵ CFU/mL of bacteria or 10² CFU/mL with the presence of symptoms diagnostic.^6,7,10 Most UTI’s do not require cultures, and urine cultures do not affect treatment for patients with simple, uncomplicated UTI (premenopausal, nonpregnant females). Other patients (pyelonephritis, males, those on recent antibiotic therapy, failed treatment, instrumentation) should have a urine culture sent.^1-7   The majority of patients have UTI due to E. coli, followed by S. saprophyticus, enterococci, or group B streptococci.^1-7 Typical antibiotics adequately cover these organisms (though treatment should take into account local sensitivities). If urine cultures are obtained, a system should be in place to follow these results. Culture results suggesting microbes not susceptible to the prescribed antibiotic should be contacted. If the patient is improved, alternative therapy may not be required, though follow up is recommended. Symptom improvement is in part due to high urinary antibiotic concentrations that result in clinical cure, even though the microbe displays in vitro resistance. If symptoms have continued, alternative therapy and follow up are recommended.

#6 Patients with asymptomatic bacteriuria should receive antibiotics, as there is significant risk for pyelonephritis and sepsis

Asymptomatic bacteriuria (ASB) is defined by bacteria in the urine with no symptoms of UTI (with > 10⁵ cfu/mL on one collection in men and two consecutive clean-catch voided specimens in women).^16,24 ASB is common, with one study finding close to 5% of sexually active young women with ASB.²⁴ However, rates approach 25-50% of women and 15-49% of men without indwelling catheters.¹⁵ ASB increases with age, anatomical abnormality, neurologic impairment, and poor hygiene.^16,25  Though ASB is common (ASB is more likely than UTI in elderly patients), ASB is not associated with long-term outcomes such as sepsis, pyelonephritis, or renal failure; however, renal transplant patients are at higher risk of pyelonephritis in the setting of ASB.^26-29 However, close to 50% of patients with ASB are treated inappropriately for UTI.³⁰

As discussed, diagnosis of UTI should be based on history and exam, not bacteriuria alone.^3,10 Unfortunately, patients may not be able to provide an accurate history or exam (take for example that patient sent from the nursing home with chronic dementia…). There are means of evaluating for UTI in these patients. A 2014 study recommended antibiotics for patients with bacteriuria and pyuria and two of the following: fever, worsening urinary frequency or urgency, acute dysuria, suprapubic tenderness, or costovertebral angle tenderness.³¹ A second way is using the following to differentiate bacteriuria and ASB:³²

• Bacteriuria but no pyuria = colonization/bacteriuria
• Pyuria alone but no bacteria = inflammation
• Pyuria + bacteriuria + nitrites = infection

Treating these patients with ASB can increase antibiotic resistance and expose patients to unnecessary risks.^16,30,33,34 Symptoms and other signs of UTI on UA/dipstick should be utilized. Bacteriuria alone is not reliable. Pregnant patients and patients undergoing urologic instrumentation or bladder surgery should be treated if ASB is found.¹⁶

What about recurrent falls or altered mental status in the elderly patient? Can’t this be chalked up to a UTI?

Remember AEIOU TIPS? Recurrent falls, dementia, altered mental status, or weakness in the elderly has a large differential. History and exam are often unreliable and may not reveal an etiology. Physicians may be tempted to blame the symptoms on UTI. However, if UTI is the underlying etiology, signs or symptoms of UTI should be present.^10,33 UA with nitrites, pyuria, and bacteriuria with signs or symptoms of UTI including suprapubic and/or CVA tenderness can be diagnostic for UTI in this population.^10,34 Another study recommends using bacteriuria with signs of systemic inflammation such as fever/hypothermia, elevated WBC/CRP, elevated blood glucose in absence of diabetes, and acutely altered mental status.³⁵ On the other hand, UA with negative nitrites and LE rules out UTI.^3,10,35 Patients with findings consistent with UTI on UA and systemic findings require treatment.³⁵ However, if UA is not definitive, then further evaluation for other conditions is needed.

Case Conclusion

Your patient has no urinary symptoms and urinary dipstick that does not appear consistent with UTI, but she is concerned with her malodorous urine. You discuss the risks of overtreatment with antibiotics. She agrees with your plan for no antibiotics and follow up.

Key Points:

– UTI is a clinical diagnosis (dysuria, frequency, etc.). Urine that is cloudy or “smelly” is not diagnostic of UTI. LE or nitrites alone without symptoms does not require treatment.

– Patients with simple, routine UTI do not require urine cultures. Patients with complicated UTI, pyelonephritis, failed treatment, or recent antibiotic therapy should have urine cultures obtained.

– Bacteriuria in the absence of symptoms defines asymptomatic bacteriuria, which should not be routinely treated.

– Patients with dementia and falls or those with altered mental status and no ability to provide a history of urinary symptoms can be difficult. Negative nitrite and LE rules out UTI in ASB and in patients for whom exam is challenging.

– Other markers of systemic inflammation should be used for diagnosis if history or exam are unreliable.

References/Further Reading:

1. Stamm WE, Hooton TM, Johnson JR, et al. Urinary tract infections: from pathogenesis to treatment. J Infect Dis. 1989; 159: 400-6.
2. Gupta K, Grigoryan L, Trautner B. Urinary Tract Infection. Ann Intern Med.2017 Oct 3;167(7):ITC49-ITC64.
3. Takhar SS and Moran GJ. Diagnosis and management of urinary tract infection in the emergency department and outpatient settings. Infect Dis Clin N Am 2014;28:33-48.
4. Stamm WE, Hooton TM. Management of urinary-tract infections in adults. N Engl J Med. 1993;329(18):1328–34.
5. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Clin Infect Dis. 1999;29(4):745–58.
6. Hooton TM. Uncomplicated urinary tract infection. N Engl J Med 2012;366(11): 1028–37.
7. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5):E103–20.
8. Meister L, Morley EJ, Scheer D, et al. History and physical examination plus laboratory testing for the diagnosis of adult female urinary tract infection. Acad Emerg Med. 2013;20(7):631-645
9. Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA 2002;287(20):2701–10.
10. Schulz L, Hoffman RJ, Pothof J, et al. Top ten myths regarding the diagnosis and treatment of urinary tract infections. Journ Emerg Med. 2016;51(1):25-30.
11. Hooton TM, Roberts PL, Cox, ME, et al. Voided Midstream Urine Culture and Acute Cystitis in Premenopausal Women. N Engl J Med 2013 November 14;369(20):1883–1891.
12. Wilson ML, Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis 2004;38(8):1150–8.
13. Walter FG, Knopp RK. Urine sampling in ambulatory women – midstream cleancatch versus catherization. Ann Emerg Med 1989;18(2):166–72.
14. Foley A, French L. Urine clarity inaccurate to rule out urinary tract infection in women. J Am Board Fam Med. 2011;24:474–5.
15. Nicolle LE. The chronic indwelling catheter and urinary infection in long-term-care facility residents. Infect Control Hosp Epidemiol. 2001;22:316–21.
16. 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.
17. Simerville JA, Maxted WC, Pahira JJ. Urinalysis: A Comprehensive Review. Am Fam Physician.2005 Mar 15;71(6):1153-1162.
18. Lammers RL, Gibson S, Kovacs D, et al. Comparison of test characteristics of urine dipstick and urinalysis at various test cutoff points. Ann Emerg Med. 2001;38(5):505-512.
19. Pappas PG. Laboratory in the diagnosis and management of urinary tract infections. Med Clin North Am. 1991;75:313.
20. Cadogan M. Urinalysis. LIFTL. https://lifeinthefastlane.com/investigations/urinalysis/. Accessed 10 December 2017.
21. Deville WL, Yzermans JC, van Duijn NP, et al. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol. 2004;4:4.
22. Sundvall PD, Gunnarsson RK. Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes. BMC Geriatr. 2009;9:32.
23. Mohr NM, Harland KK, Crabb V, et al. Urinary Squamous Epithelial Cells Do Not Accurately Predict Urine Culture Contamination, but May Predict Urinalysis Performance in Predicting Bacteriuria. Acad Emerg Med. 2016;23:323–330.
24. Hooton TM,Scholes D, Stapleton AE, et al. A prospective study of asymptomatic bacteriuria in sexually active young women. N Engl J Med. 2000 Oct 5;343(14):992-7.
25. Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am 1997;11:647–62.
26. Burke JP. Antibiotic resistance—squeezing the balloon? JAMA 1998;280:1270–1.
27. Abrutyn E, Mossey J, Berlin JA, et al. Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med. 1994;120:827-33.
28. Fiorante S, Fernandez-Ruiz M, Lopez-Medrano F, et al. Acute graft pyelonephritis in renal transplant recipients: incidence, risk factors and long-term outcome. Nephrol Dial Transplant. 2011;26: 1065-73.
29. Fiorante S, Lopez-Medrano F, Lizasoain M, et al. Systematic screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney Int. 2010;78:774-81.
30. Kelley D,Aaronson P, Poon E, et al. Evaluation of an antimicrobial stewardship approach to minimize overuse of antibiotics in patients with asymptomatic bacteriuria. Infect Control Hosp Epidemiol. 2014 Feb;35(2):193-5.
31. Mody L, Juthani-Mehta M. Urinary Tract Infections in Older Women: A Clinical Review. JAMA. 2014;311(8):844-854.
32. Cunha B. Therapeutic approach to treating urinary tract infections. In: Cuhna B, ed. Urinary tract infections: current issues in diagnosis and treatment. Antibiotics for Clinicians. 1998;2(suppl 2):35-40.
33. Bartlett JG. A call to arms: the imperative for antimicrobial stewardship. Clin Infect Dis 2011; 53(Suppl 1):S4–7.
34. 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.
35. Ninan S,Walton C, Barlow G. Investigation of suspected urinary tract infection in older people.  2014 Jul 3;349:g4070.