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Urinary tract infection (UTI) is usually bacterial in etiology, may be
either acute or chronic, and may affect any part of the upper or lower
urinary system. UTI is often classified as either uncomplicated or
complicated based upon patient characteristics and on the clinicalsetting
in which the infection is acquired (e.g., community-acquired vs. health
Uncomplicated UTI occurs in women who are otherwise healthy and
have normalstructure and function of the urinary tract. These infections
are primarily caused by Escherichia coli (75%–95% of infections) and
other gram-negative bacilli, as well as gram-positive organisms such as
Staphylococcus saprophyticus and Enterococcus.
Symptoms commonly associated with lower UTI (e.g., cystitis) include
dysuria, frequent urination, suprapubic pain, hematuria, and back pain.
Patients with upper tract infection (e.g., acute pyelonephritis) often
present with similar findings as well as loin pain, costovertebral angle
tenderness, fever, chills, nausea, and vomiting.
The cornerstone of effective treatment of UTI is appropriate selection
and use of antibiotics. Resistance among E. coli and other uropathogens
is increasing and is an important consideration in antibiotic selection.
Consensus clinical guidelines recommend trimethoprim–
sulfamethoxazole (TMP–SMX) for 3 days, nitrofurantoin for 5 days, or
a single dose of fosfomycin as preferred first-line antibiotics for
treatment of acute uncomplicated cystitis in women.
Fluoroquinolones are commonly used for treatment of UTI and are
highly effective. However, growing concerns of increasing resistance
and potential adverse effects limit the use of fluoroquinolones in
uncomplicated UTI to patients unable to receive other preferred agents
because of drug resistance, allergies, or other contraindications. Similar
recommendations restrict the use of β-lactam antibiotics for
Complicated UTI is associated with abnormalities of the urinary tract
that interfere with normal urine flow or function; men, children, patients
with diabetes, pregnant women, and hospitalized patients are examples
of commonly affected populations. Complicated infections are
frequently caused by drug-resistant gram-negative bacilli or other
pathogens with reduced antibiotic susceptibility. Antibiotic selection for
complicated UTI should be guided by culture and susceptibility testing,
and patients usually require longer durations of antibiotic therapy (7–14
Pyelonephritis may be more severe in presentation and is often
associated with bacteremia and other complications. However, most
cases are uncomplicated and can be treated on an outpatient basis with
oral antibiotics such as fluoroquinolones. Patients who cannot take oral
antibiotics or who are clinically unstable should be hospitalized for initial
treatment with intravenous antibiotics.
Recurrent UTI may be caused by either reinfection or relapse because
of treatment failure. Relapse usually occurs within two weeks of the
original infection and is caused by the same pathogen. Selection of
antibiotics for treatment of relapsed UTI should be guided by culture
and susceptibility testing, and the duration of antibiotic therapy should be
Recurrent UTI, which occurs more than 2 weeks after the original
infection, is treated as a new infection with antibiotic considerations
similar to those for the initial infection. Women with frequent infections
(3 or more/year) may be considered for chronic prophylaxis therapy.
Women with identifiable causes of reinfection (e.g., associated with
sexual intercourse) may self-administer prophylactic antibiotics.
5 bacteria per milliliter of urine in the
absence of clinicalsigns/symptoms of UTI) is particularly common in
children, the elderly, pregnant women, and in patients with diabetes.
Treatment of asymptomatic bacteriuria for prevention of subsequent
infection and associated complications is routinely recommended in
children and pregnant women. However, treatment of the elderly and
patients with diabetes has not shown clear benefits and is not currently
Prostatitis is a relatively common infection in men and is caused by
bacteria similar to those causing uncomplicated UTI in women. Acute
bacterial prostatitis is usually treated with either a fluoroquinolone or
TMP–SMX for a period of 2 to 4 weeks. Chronic prostatitis persists in
a small percentage of men after acute infection and is usually treated
for 4 to 6 weeks, although longer courses may sometimes be required.
Incidence, Prevalence, and Epidemiology
Urinary tract infection (UTI) is an acute or chronic infection, usually bacterial in
origin, that may affect any part of the upper or lower urinary system.
Infections of the bladder are referred to as cystitis, and infections involving the
parenchyma of the kidneys are known as pyelonephritis. UTIs occur frequently in
both community and hospital environments and are the most common bacterial
1–3 The term UTI encompasses a spectrum of clinical entities
ranging in severity from asymptomatic infection to acute pyelonephritis with
1–4 Approximately 8 to 9 million cases of acute cystitis and 250,000 cases of
acute pyelonephritis occur annually in the United States, resulting in more than
6 Direct costs associated with the diagnosis and treatment
of UTI have been estimated at approximately $3 billion annually in the United
7 UTI is predominantly a disease of females with more than 50% of all
women experiencing at least one infection during their lifetime.
likelihood of developing a UTI is approximately 30 times higher in women than in
8 Women have more UTIs than men, probably because of anatomic and
physiologic differences. The female urethra is relatively short and allows bacteria
easy access to the bladder. In contrast, males are partly protected because the urethra
is longer and antimicrobial substances are secreted by the prostate.
Approximately 1% of boys and 3% to 5% of girls experience at least one UTI
during childhood and 30% to 50% of these will have at least one recurrence.
incidence of UTI in neonates is about 1% and is more frequent in male neonates,
frequently because of congenital structural abnormalities.
newborns with UTI was earlier reported to be as high as 10%10
now much lower because of an increased awareness of the high frequency of UTI in
children, improved diagnostic techniques, and more effective management.
males also occur with increased frequency after age 50, when prostatic obstruction,
urethral instrumentation, and surgery influence the infection rate. Infection in younger
men is rare and requires careful evaluation for urinary tract pathology.
Of women between the ages of 15 and 24 years, 1% to 5% have bacteriuria; the
incidence increases 1% to 2% for each decade of life, and approximately 10% to
20% of women are bacteriuric after age 70.
elderly living at home have bacteriuria, and this number increases to 20% to 50% in
extended care facilities and 30% in hospitals.
16 For those 65 years or older the
frequency of UTI continues to rise with increasing age. Most UTI in these patients are
asymptomatic, but it may also result in symptomatic infection.
higher UTI rates in elderly persons include the high prevalence of prostatic
hypertrophy in men, incomplete bladder emptying caused by underlying diseases or
medications, dementia, and urinary and fecal incontinence.
in old age is associated with decreased survival is controversial
presence of asymptomatic bacteriuria is associated with decreased functional ability
15 and symptomatic UTI has been independently
associated with a threefold increased risk of vertebral fractures.
UNCOMPLICATED VERSUS COMPLICATED INFECTIONS
An important distinction in the characterization and treatment of UTI is that of
uncomplicated versus complicated infections. Uncomplicated UTI, either cystitis or
pyelonephritis, occurs in women who have normal structure and function
of the genitourinary tract and who have no other factors which would put them at risk
for more severe or complex infections.
20 By contrast, complicated infections are
those which are associated with conditions that increase the risk for acquiring
infection, the potential for serious outcomes, or the risk for therapy failure. Such
conditions are often associated with genitourinary tract abnormalities that may
interfere with normal urine flow. Infections in men, children, and pregnant women
are automatically considered complicated, as are those which are health care–
associated in origin. Other examples of complicated infections include those
associated with structural and neurologic abnormalities of the urinary tract,
metabolic or hormonal abnormalities, impaired host responses, instrumentation and
catheterization of the urinary tract, and those caused by unusual pathogens (e.g.,
may be caused by pathogens associated with either community-acquired or health
care–associated infections, depending on the source of bacterial acquisition and
specific underlying patient risk factors. Complicated infections are also more often
polymicrobial in etiology, associated with more antibiotic-resistant pathogens, and
generally require a longer duration of therapy.
Most UTIs are caused by gram-negative aerobic bacilli from the intestinal tract.
Escherichia coli cause 75% to 95% of community-acquired, uncomplicated
20 Coagulase-negative staphylococci (e.g., Staphylococcus saprophyticus)
account for another 5% to 20% of UTIs in younger women.
Enterobacteriaceae (e.g. Proteus mirabilis, Klebsiella) and Enterococcus faecalis
20 Uncomplicated infections are nearly always caused
HEALTH CARE–ASSOCIATED INFECTIONS
UTIs occur in up to 10% of hospitalized patients and represent 20% to 30% of all
these infections. Other gram-negative organisms, such as Pseudomonas aeruginosa,
Klebsiella, Proteus, Enterobacter, and Acinetobacter, cause significantly more
infections (up to 25%) than in the community setting.
common pathogen in hospital-acquired UTIs and causes approximately 15% of
23 UTIs because of Staphylococcus aureus are usually the result of
hematogenous spread, although this pathogen is also associated with urinary
22–24 Finally, Candida is a common pathogen in hospital-acquired
infections and may be involved in 20% to 30% of cases.
monomicrobial uncomplicated infections, UTIs associated with structural
abnormalities or indwelling urinary catheters are often caused by multiple
Pathogenesis and Predisposing Factors
The typical pathway for the spread of bacteria to the urinary tract is the ascending
route. A UTI usually begins with heavy and persistent colonization of the introitus
(i.e., vaginal vestibule and urethral mucosa) with intestinal bacteria. Colonization of
the urethra leads to retrograde infection of the bladder and the development of
The bladder has defense mechanisms that prevent spread of the infection after
urethral colonization has occured.
22 Urination washes bacteria out of the bladder
and is effective if urine flows freely and the bladder is emptied completely.
Substances in the urine, including organic acids (which contribute to low pH) and
urea (which contributes to high osmolality), are antibacterial. The bladder mucosa
also has antibacterial properties.
22 Lastly, other substances, including
immunoglobulin A and glycoproteins (e.g., Tamm–Horsfall protein), are actively
secreted into the urine and prevent adherence of bacteria to uroendothelial
Focal renal involvement leading to pyelonephritis may result from the spread of
bacteria via the ureters and may be facilitated by vesicoureteral reflux or decreased
ureteral peristalsis. Ureteral peristalsis is decreased in pregnancy, by ureteral
obstruction, or by gram-negative bacterial endotoxins.
by cystitis alone or by anatomic defects.
A variety of factors contribute to the development of UTI, for example expression
of bacterial virulence factors such as specific adhesin molecules, bacterial
polysaccharides, and bacterial enzymes. Other factors predisposing to the
development of UTI are dependent on the host and may include extremes of age,
female sex, sexual activity, use of contraception, pregnancy, urinary tract
instrumentation or catheterization, urinary tract obstruction, neurologic dysfunction,
renal disease, previous antimicrobial use, and expression of A, B, and H blood group
oligosaccharides on the surface of epithelial cells.
The incidence of bacteriuria in pregnant women is as high as 17%, which is
approximately twice that of similarly aged nonpregnant women.
of acute symptomatic pyelonephritis in pregnant women with untreated bacteriuria
also is high and may reach 40%.
3 Many factors contribute to the increased
susceptibility of the pregnant female to infection; these include hormonal changes,
anatomic changes, progressive urinary stasis, and glucose in the urine.
changes have also been linked to a significantly higher risk of UTI in menopausal
3 Estrogen promotes an acidic vaginal pH and proliferation of normal flora
such as Lactobacillus, both factors which reduce pathogenic colonization of the
vagina. Reduction of estrogen production during menopause allows significant
colonization of the vaginal tract with E. coli and other enteric bacilli, thus
predisposing to subsequent infection.
Renal disease increases the susceptibility of the kidney to infection.
incidence of UTI among renal transplant recipients ranges from 35% to 80% without
prophylactic antibiotic therapy.
30 Patients with spinal cord injuries, stroke,
atherosclerosis, or diabetes may have neurologic dysfunction predisposing to UTI.
The neurologic dysfunction can cause urinary retention, requiring catheterization.
Furthermore, prolonged immobilization facilitates hypercalciuria and stone formation
Previous antimicrobial use (within the previous 15–28 days) for UTI or other
infections increases the relative risk for UTI in women threefold to sixfold.
proposed mechanism for this is alteration of normal flora of the urogenital tract and
predisposition to colonization with pathogenic bacterial strains.
Diabetes mellitus is associated with a higher risk for UTI because of glucose in the
urine, promoting bacterial growth and impairing leukocyte function. Anatomic,
neurologic, and immunologic abnormalities of the urinary tract in diabetics contribute
to the risk of infection, often because of more frequent urinary tract
32 Several studies have documented a twofold to threefold increase
in UTI in women with diabetes compared to those without; rates of relapses and
reinfections, as well as complications such as pyelonephritis, are also higher.
Autonomic neuropathy associated with diabetes also contributes to increased
frequency and severity of UTI.
Finally, studies have supported an association between sexual intercourse and UTI
among otherwise healthy women.
34 Specific contraceptive practices,
particularly the use of spermicides, and the use of a diaphragm, cervical cap, or
condom in combination with spermicidal jelly increases the risk of UTI compared
with the use of the barrier method alone.
34 Diaphragm users are approximately 3
times more likely to experience a UTI than women using other contraceptive
methods, especially when the diaphragm is used in conjunction with spermicidal
27 Oral contraceptive use has also been linked with increased risk of UTI,
although this is still unclear.
34 The exact mechanisms of infection related to
sexual intercourse and contraceptive methods are unclear but appear to be related to
alterations in vaginal flora that allow for bacterial overgrowth and subsequent
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