Urinalysis (UA) and the Diagnosis of UTIs

Urinalyses (UAs) are one of the most commonly ordered lab tests in primary care, and
urinary tract infections (UTIs) are very common in adults and not uncommon in
children. However, the interpretation of UAs is not as straightforward as it may seem,
and this has significant implications for diagnoses and treatment. Also treatment
recommendations have changed! Enteric bacteria (in particular, Escherichia coli)
remain the most frequent cause of UTIs, although the distribution of pathogens that
cause UTIs is changing. More important is the increase in resistance to some
antimicrobial agents, particularly the resistance to trimethoprim-sulfamethoxazole
seen in E. coli.

Urinary tract infections (UTIs) are among the most common bacterial infections. It has
been estimated that symptomatic UTIs result in as many as 7 million visits to
outpatient clinics annually 1. The annual cost to the health care system of the United
States attributable to community-acquired UTI alone is estimated to be approximately
$1.6 billion4.

UTIs are challenging, not only because of the large number of infections that occur
each year, but also because the diagnosis of UTI is not always straightforward.
Physicians must distinguish UTI from other diseases that have a similar clinical
presentation. Some UTIs are asymptomatic or present with atypical signs and
symptoms. Because of these factors, physicians frequently rely on a small number of
imperfect laboratory tests to augment clinical impressions. None of these tests used
individually have adequate sensitivity and specificity.

Clinical symptoms of UTIs/cystitis include frequent voiding, burning during and after
voiding, suprapubic pain, and/or hematuria +/- cloudy urine with a rapid onset over 24
hours of symptoms. Symptoms of pyelonephritis can include the above and fever,
chills, and flank pain.
Interstitial cystitis (IC) is a long-term (chronic) inflammation of the bladder wall. The
cause is unknown. It is often misdiagnosed as a urinary tract infection. This condition is
most common in ages 30-40, and women are 10 times more likely to have IC than men.
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 Common symptoms of interstitial cystitis include pain during intercourse, pelvic pain,
urinary discomfort, urinary frequency, and urinary urgency.
Asymptomatic bacteriuria , a significant number of bacteria in the urine that occurs
without usual symptoms such as burning during urination or frequent urination, and
with no pyuria/LE, is common and may not need treatment, which makes it different
from a bacterial urinary tract infection.

Preparation for UA
It is suggested that first-voided specimens (early morning) that have been stored in the
bladder for at least 4 hours provide the most accurate results. At least 2 hours are
required to allow the growth of bacteria – so ask the patient when they previously
voided.
*Goldmans Cecil Medicine 24th Ed Midstream clean-catch is the method most commonly used in clinical practice

The UA dipstick is very helpful. Leukocyte esterase has a sensitivity of 75% and
specificity of 98% for the detection of a UTI. [25] A positive nitrite test has a specificity
of 90% but a sensitivity as low as 30% for a UTI. [25] Combination of the 2 tests leads to
a more accurate detection of a UTI with sensitivity of up to 88%. [25]

pH reflects the body’s ability to maintain normal acid-base balance. Infection with
urease producing bacteria can result in pH >7-7.5.
Specific gravity correlates well with urine osmolality and provides hydration status and
concentrating ability of kidneys.
Nitrites, a rapid indirect test for asymptomatic bacteriruia. E Coli, Klebsiella and
Proteus produce nitrite from nitrate, Pseudomonas, enterococci and S Saprophyticus
do not. (43) 4 hours of bladder incubation are required for bacteria to convert nitrate
to nitrite. It is therefore not uncommon to have a nitrite negative urine test result that
later shows a positive urine culture result
Leukocyte esterase (LE) detects WBCs via esterase, an enzyme released by WBCs after
2 hours, detects the equivalent of 6 or more WBC/hpf. Sensitivity is 94% when a UTI is
suspected clinically. However false-positive results are common when the urine is
contaminated with bacteria present in vaginal fluid, when the specimen contains
eosinophils or Trichomonas, and so a UA micro and/or urine culture is necessary if
nitrite negative.
*Nursing Times.net 22 March, 2005 VOL: 101, ISSUE: 12, PAGE NO: 60

The absence of leukocytes and nitrites in a fresh urine sample confirms its sterility (or
inadequate bladder incubation time), while the presence of one of the markers
suggests a possible urinary tract infection
Heme/‘Blood’ on dipstick does not necessarily mean there are RBCs present, a UA
micro is necessary to evaluate for hematuria (>3 RBC/hpf).
Proteinuria is a common finding in UTI. Concern for other causes of proteinuria would
require a follow-up test such as UMAC or 24 hour urine for protein.

UA micro is necessary in many cases to accurately diagnose a UTI. A ‘positive’ UA does

not necessarily mean a UTI as other conditions may cause that, and a negative UA does
not necessarily rule-out a UTI.

White blood cell count (WBCs) > 5-10 WBC is considered to be pyuria, which usually
indicates a UTI. However white cells from the vagina and cervical infections and
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 external meatus in men and women may contaminate the urine.
Red Blood Cell (RBCs) >3/hpf in the urine is abnormal. Hematuria (blood in urine)
associated with cystitis or urethritis will usually resolve after treatment. Persistent
hematuria may indicate disease such as malignancy, kidney stones, glomerulonephritis,
etc.
*NT
Epithelial cells in urine usually indicate contamination of the specimen from the distal
urethra in men and the opening of the vagina in women. *NT
Bacteriuria is defined as the presence of bacteria in the urine; however, because the
specimen can be contaminated with periurethra flora during collection, infection is
confirmed by counting the number of bacteria.

Urine Cultures (UC) determine colony count and identify bacteria, and antimicrobial
susceptibility. The time the urine resides in the bladder (bladder incubation time) is an
important determinant of the magnitude of the colony count. The concept that more
than 100,000 CFUs/ml indicates a UTI was based on morning collections of urine from
adult women. Sometime even 1-10,000 CFUs/ml (or fewer) is significant (per the
Infectious Diseases Society of America definition of cystitis). 1/3 of young women with
symptomatic UTI have < 10,000 CFU/ml. In infants and children 50,000 CFU per ml of a
single urinary pathogen is considered significant, when pyuria is present.
UC may not be necessary as part of the evaluation of outpatients with uncomplicated
UTIs [55, 56]. However, urine cultures are necessary for all children, and adults with
recurrent UTIs, treatment failures, or complicated UTIs.

Treatment of UTIs in Children (per Up-To-Date)

Recommendations for treatment of UTIs in children has changed over the past 10
years. Diagnosis is made on the basis of the presence of both pyuria and at least 50
000 colonies per mL of a single uropathogenic organism in an appropriately collected
specimen of urine. Sensitivities should be done so antibiotic choice can be adjusted if
necessary. Amoxicillin and ampicillin are not routinely recommended for empiric
therapy because of the high rate of resistance of E. coli. Similarly, amoxicillin-
clavulanate, first-generation cephalosporins (eg, cephalexin), and TMP-SMX should be
used with caution because of the increasing rates of resistance to these drugs in some
communities. Third-generation cephalosporins (eg, cefotaxime, ceftriaxone,
cefepime) are appropriate first-line agents for empiric treatment of UTI in children.
Fluoroquinolones (eg, ciprofloxacin) are effective for E. coli, and resistance is rare.
However, the safety of quinolones in children is still under study [28 Ciprofloxacin
should not be used as a first-line agent. The American Academy of Pediatrics (AAP)
Committee on Infectious Diseases recommends that the use of ciprofloxacin for UTI in
children be limited to UTI caused by Pseudomonas aeruginosa or other multidrug-
resistant, gram-negative bacteria [28].
After 7 to 14 days of antimicrobial treatment, close clinical follow-up monitoring should
be maintained to permit prompt diagnosis and treatment of recurrent infections.
Ultrasonography of the kidneys and bladder should be performed to detect anatomic
abnormalities. Pediatrics 2011;128: 595–610
http://pediatrics.aappublications.org/content/early/2011/08/24/peds.2011-1330

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 Treatment of UTIs in Adults per Up-To-Date
Nitrofurantoin 100 mg bid for 5-7 days shows clinical efficacy 90 to 95% based on
randomized trials [39-42]. Nitrofurantoin should be avoided if there is suspicion for
early pyelonephritis, and is contraindicated when creatinine clearance is <60
mL/minute. Trimethoprim-sulfamethoxazole TMP-SMX DS [160/800 mg] bid for 3-7
days shows clinical efficacy rate 86 to 100 % [39,40,43,44]. Empiric TMP-SMX should be
avoided if the prevalence of resistance is known to exceed 20 percent [22,23] or if the
patient has taken TMP-SMX for cystitis in the preceding 3 months [18,19]. In some
regions trimethoprim (100 mg twice daily for three days) is used in place of TMP-SMX
and is considered equivalent [35]. If factors preclude use of the above antibiotics,
fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin in 3-day regimens) are
reasonable, though, when possible, fluoroquinolones should be reserved for important
uses other than acute cystitis . Nitrofurantoin and beta-lactams should usually not be
used in men with cystitis, since they do not achieve reliable tissue concentrations and
would be less effective for occult prostatitis.

Conclusion
Most patients with uncomplicated acute cystitis have cases that are clinically
straightforward, and they may not require any laboratory testing beyond urinalysis. For
a significant number of patients, however, the clinical history and physical findings
alone may be insufficient to make a definitive diagnosis of UTI. For those patients and
for patients with complicated UTIs, laboratory tests are necessary to make the
diagnosis and to provide specific information regarding the identity and the
antimicrobial susceptibility pattern of pathogens. Both the laboratory diagnosis and the
clinical diagnosis of laboratory test results must be made in light of the method of
collection used. Of the available laboratory tests, urinalysis is helpful primarily as a
means of excluding bacteriuria, but it is not a surrogate for culture. Although cultures
identify pathogens, the accurate interpretation of culture results requires clinical
information that is usually available only to the clinician. We hope that primary care
providers will understand both the strengths and the limitations of the laboratory-
based diagnostic studies for UTIs that have been reviewed, and that they will
incorporate this understanding with current treatment guidelines [65] to optimize
patient care.

References:

1. Schappert SM. Ambulatory care visits to physician offices, hospital outpatient

departments, and emergency departments: United States, 1997. Vital Health
Stat 13 1999;143:i-i. 1–39. Search Google Scholar.
2. Stamm WE. Scientific and clinical challenges in the management of urinary
tract infections. American Journal of Medicine 2002; 113:1-4. MedlineWeb of
Science.
3. Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of
positive blood cultures in the 1990s: a prospective comprehensive evaluation
of the microbiology, epidemiology, and outcome of bacteremia and fungemia
in adults.Clin Infect Dis 1997;24:584-602. Abstract/FREE Full Text
4. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and
economic costs. Am J Med 2002; 113:5-13. Web of Science

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 Questions: Please reply to this e-mail, and your questions(s) will be directed to the
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