US Pharm. 2013;38(11):65-68.
ABSTRACT: Urinary tract infection (UTI) is one of the most
commonly diagnosed infections in both outpatient and inpatient
populations. In order to make an accurate diagnosis, it is essential for
practitioners to understand the value and limitations of urinalysis and
urine culture. Use of these tests in conjunction with an assessment of
urinary symptoms will yield a diagnosis of either asymptomatic
bacteriuria or symptomatic UTI. Pharmacists can play a key role in
recommending that antibiotic therapy be withheld when it is not
indicated, in addition to providing guidance on appropriate antibiotic
selection when treatment is warranted.
Urinalysis is a valuable diagnostic tool for many common disease
states. Urinalysis is the most frequently used test for the evaluation
of potential urinary tract infection (UTI). In addition, it can provide
useful information related to screening and diagnosis of other
conditions, including malignancy, proteinuria, glycosuria, ketonuria,
and renal calculi.1 Accurate interpretation of urinalysis
results is a key concept for health care providers in order to diagnose
and treat patients appropriately. This article will focus primarily on
the interpretation of urinalysis and subsequent urine culture in the
diagnosis and treatment of UTIs.
UTI is the second most common type of infection, accounting for
approximately 10 million visits to health care providers in the United
States each year.2 Many of these visits take place in the
emergency department, where urinalysis can provide rapid diagnostic
results. However, because urinalysis is so commonly ordered in the
emergency care setting, there is concern that misinterpretation may lead
to overtreatment of UTI and increased antibiotic use. Treatment of a
UTI should never be initiated based upon urinalysis alone; patient
history and subsequent urine culture results are extremely important for
diagnosing UTI. In a recent study of 153 women aged 70 years and older
with a diagnosis of UTI made in the emergency department, 43% of
patients did not have microbiological evidence of a UTI, yet 95% of
culture-negative patients received antibiotic therapy.3
Overtreatment of UTI leads to higher health care costs, increased
antibiotic exposure, a greater number of adverse reactions,
antimicrobial resistance, and other unintended outcomes, such as Clostridium difficile infection.
It is vital to understand the symptoms of UTI that may prompt an
order for a urinalysis and urine culture. Urinary symptoms should be
used in conjunction with test results to diagnose UTI. While many of the
symptoms seem intuitive, there have been some recent changes to the
definitions of the nonspecific symptoms that many health care providers
have come to associate with UTI.
Cystitis/Lower UTI Symptoms: The most common
symptoms associated with lower UTI include dysuria or acute pain,
frequent urination, urgency, and incontinence. Occasionally, hematuria,
cloudy urine, or foul-smelling urine may be present.4,5
Pyelonephritis/Upper UTI Symptoms: Compared with
cystitis, pyelonephritis often has a more severe, systemic presentation.
In addition to the urinary symptoms seen in cystitis, patients may also
present with suprapubic pain, costovertebral angle tenderness (flank
pain), fever, chills, elevated WBC count, nausea, and vomiting.4,5
Nonspecific Symptoms: Nonspecific symptoms, most
notably mental-status changes, have become associated with a suspicion
of UTI in elderly patients. This can been attributed to the inclusion of
these generalized symptoms in previous consensus-based criteria for
diagnosing UTI in residents of skilled nursing facilities.3
It remains controversial whether isolated nonspecific symptoms in the
elderly can be directly related to UTI. The most recent definitions of
UTI in long-term care facilities do not include acute mental-status
change as a symptom of UTI in noncatheterized patients. In patients
without an indwelling catheter, mental-status change or acute functional
decline without an alternative diagnosis may be used as a diagnostic
criterion for UTI, but only if leukocytosis is present as well.5
Based on this definition, less emphasis should be placed on nonspecific
symptoms unless the patient is catheterized or has unexplained
There are several factors to consider when evaluating urinalysis for
indicators of infection. The most obvious indicator of bacterial
infection in the urine is the presence of bacteria; this is often
quantified in terms of the number of bacteria per high-power field
(HPF). Any amount of bacteria in the urine may suggest UTI in a
symptomatic patient, but the threshold for the classic definition of
bacteriuria is 5+, which is roughly equivalent to 100,000 colony-forming
units (CFUs)/mL.1 An alternative definition for bacteriuria
is 2+ present on urinalysis (representing 100 CFU/mL); this may be
considered positive in selected populations, such as catheterized or
strongly symptomatic patients.
Pyuria, which is defined as urine WBC >10 or positive leukocyte
esterase, indicates the presence of inflammation. However, pyuria does
not necessarily mean that the inflammation is a result of infection.
Pyuria is associated with low specificity and positive predictive value,
yet its absence virtually eliminates infection as a cause, with a
negative predictive value of nearly 90%.1,3
Evaluation for the presence of nitrites in the urine is also of
value. A test that is positive for nitrites in the urine indicates the
presence of an organism that reduces nitrate.1 However, not
all urinary pathogens are nitrate reducers. A positive test is highly
specific for bacterial infection, but a negative test does not exclude
infection, giving this test low sensitivity.1 In addition,
false-positive results for nitrite will occur if the dipstick is exposed
to air or phenazopyridine, a common prescription and OTC product (e.g.,
Pyridium, AZO) used as a urinary analgesic.1
Urinalysis interpretation is summarized in TABLE 1, with the first four tests most commonly evaluated for information leading to the diagnosis of UTI.1
At many institutions, a reflex urine culture is sent if the urine meets
set criteria regardless of patient symptoms. Frequently, if any of the
first four tests listed in TABLE 1 are positive, a reflex urine
culture will be ordered. This can create a situation in which a positive
urine culture may prompt treatment with antibiotics, even if the
patient is asymptomatic. Overtreatment of asymptomatic bacteriuria is a
common occurrence that can be prevented with careful application of
Approach to the Asymptomatic Patient
A therapeutic challenge arises when a patient has urinalysis findings
or culture results that are consistent with UTI, yet does not
experience any urinary symptoms. The prevalence of this condition, known
as asymptomatic bacteriuria, increases with age.6,7
Asymptomatic bacteriuria has been reported in 50% of women in long-term
care facilities, and the prevalence in men drastically increases in
those older than 60 years.6 Routine screening of asymptomatic
patients is not recommended, according to the Infectious Diseases
Society of America guidelines.6 The only populations with a
proven benefit from urinalysis and culture screening are pregnant
patients and patients with a planned transurethral resection of the
prostate or other urologic procedure in which mucosal bleeding is
expected.6 Treatment also may be considered in women with bacteriuria more than 48 hours after catheter removal.6,8
If asymptomatic bacteriuria is identified in a patient from one of
these populations, treatment should be initiated as described in TABLE 2.6,8-11
Antibiotic therapy should be started empirically, but it may require
modification depending upon the organism identified in the urine
Approach to the Symptomatic Patient
Once a diagnosis of UTI has been made based upon symptoms and
urinalysis results, the next step is to start empirical antibiotic
therapy and await culture and susceptibility results. As previously
discussed, UTI symptoms may be defined as lower (cystitis), upper
(pyelonephritis), or nonspecific. Another classification of UTI that can
determine treatment and therapy duration is uncomplicated versus
Uncomplicated UTI is defined as a UTI without structural or urologic abnormalities.12 Uncomplicated cystitis is often associated with healthy community-dwelling women.13
Uncomplicated infections are rare in males because of the anatomical
feature of a longer urethra, which protects against the ascending spread
of bacteria. Uncomplicated UTI in young males may be a result of
homosexual activity or noncircumcision, but otherwise UTIs in men are
often classified as complicated.14
Complicated UTI has various definitions, but the most
consistent patient features are presence of foreign body, obstruction,
immunosuppression, renal failure or transplantation, urinary retention,
Antimicrobial selection for treatment of symptomatic UTI should be
based on the most likely pathogens. The most common pathogen in
uncomplicated infections is Escherichia coli, followed by other Enterobacteriaceae, including Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus.13
Local susceptibility data on these uropathogens should be used to
direct empirical antibiotic prescribing, since resistance has increased
in recent years. In patients with complicated UTI, the same pathogens
may be present; however, more resistance is seen with gram-negative
organisms. Some of the most common resistant uropathogens are
extended-spectrum beta-lactamases, which are common with E coli, K pneumoniae, and P mirabilis species.12 Other multidrug-resistant pathogens, such as Serratia, Citrobacter, Enterobacter, Pseudomonas, and Acinetobacter
species, become more common in health care–associated infections.
Infections with gram-positive organisms such as staphylococci and
enterococci are also more common in complicated UTI.12 If a
urinary catheter is in place, removal of the catheter and culture from
midstream urine or a fresh catheter should be used to direct therapy.8
Once the likely pathogens have been established, an appropriate
antibiotic that will achieve good urinary concentrations should be
prescribed. Urine culture results should be used to de-escalate or
change therapy, if needed, and the recommended duration of therapy
should be followed to prevent excessive antimicrobial exposure. TABLE 3 provides the recommended agents and therapy durations for symptomatic UTI.13,14
Clinical interpretation of urinalysis and urine culture results
requires both an understanding of the significance of test
characteristics and the incorporation of patient symptoms. At many
institutions, pharmacists play a key role in reviewing positive
urinalysis and urine culture results as a part of antimicrobial
stewardship and clinical activities. It can be tempting to simply
recommend an antibiotic based on test results, but in order to prevent
overtreatment of asymptomatic patients, a careful review of symptoms
should also be conducted. Pharmacists can be proactive in implementing
antibiotic prescribing pathways that provide empirical antibiotic
recommendations utilizing local susceptibility data.
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