Urinary Tract Infection: An Overview
BEN J. BARNETT, MD,* DAVID S. STEPHENS, MOt
ABSTRACT: Urinary tract infection (UTI) re-
mains very common. As many as 50% of women
report having had at least one UTI in their life-
times. Urinary tract infection is the most com-
mon cause of infection in nursing home resi-
dents and the most common source of bacter-
emia in the elderly population. Urinary tract
infection occurs in patients with structurally
or functionally abnormal urinary tracts (com-
plicated UTI) and in patients with anatomi-
cally normal urinary tracts (uncomplicated
UTI). Escherichia coli (E coli) is the most com-
mon cause of uncomplicated UTI, whereas an-
tibiotic-resistant Enterobacteriaceae, entero-
cocci, and Candida species often are the
causes of complicated UTI. In this article we
review current concepts of the epidemiology,
microbiology, pathophysiology, clinical mani-
festations, diagnosis, and treatment of urinary
tract infection. KEY INDEXING TERMS: Uri-
nary tract infection; Pyelonephritis; Infection
in the elderly patient. [Am J Med Sci 1997;
314(4):245-249.]
T he phrase "urinary tract infection" (UTI) is a
general term that refers to an infection, usually
bacterial in etiology, anywhere along the urinary
tract from the urethral meatus to the perinephric
fascia. Structures in this pathway include the ure-
thra, bladder, ureters, and the renal pelvis and pa-
renchyma. Associated structures that also become
infected and that may serve as foci of recurrent UTI
are the prostate, epididymis, and perinephric fascia.
Specific types of urinary tract infection include ure-
thritis, an infection limited to the urethra; cystitis,
an infection of the bladder; and pyelonephritis, a
more extensive infection involving the upper urinary
tract structures.
From the *Division of Infectious Diseases, Emory University
School of Medicine, Atlanta, Georgia, and the tVeterans Adminis-
tration Medical Center, Decatur, Georgia.
Correspondence: David S. Stephens, MD, Division of Infectious
Diseases, Emory University School of Medicine, 69 Butler Street
Southeast, Atlanta, GA 30303.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Although these definitions are descriptive anatomi-
cally, the terms "uncomplicated" versus "complicated"
UTI are more clinically useful. 1 Uncomplicated UTI
most often occurs in patients with anatomically normal
urinary tracts, resolves with short courses of antibiotics,
and has little effect on long-term renal function. Compli-
cated UTI occurs in patients with structurally or func-
tionally abnormal urinary tracts and often is caused
by antibiotic-resistant bacteria. This includes intrinsic
abnormalities such as renal stones or prostatic hyper-
trophy, as well as external devises such as indwelling
urethral catheters. Complicated UTI is difficult to cure
and to be fully eradicated often necessitates surgery or
other resolution of the abnormality. The risk of long-
term damage to renal function is increased with compli-
cated UTI.
Urine normally is sterile. However, not all bacte-
ria are equally likely to cause infection in the urinary
tract, and some bacteria isolated from urine may be
contaminants from surrounding structures. There-
fore, a "uropathogen" is defined as an organism that,
when isolated from urine, is likely to be a cause of
disease. Uropathogens, such as E coli, other Entero-
bacteriaceae, enterococci, and Staphylococcus sapra-
phyticus (S saprophyticus), can possess virulence
factors that allow colonization and invasion of the
urinary tract epithelium first and then multiplica-
tion in urine. Other organisms, such as lactobacilli,
a-hemolytic streptococci, or anaerobes do not grow
well in urine and, in the absence of evidence of en-
teric or vaginal fistulae, usually are considered to be
contaminants when isolated in urine.
Epidemiology
Infection of the urinary tract is very common, ac-
counting for more than 6 million outpatient physi-
cian office visits every year.2 In neonates, UTI is
more common in boys, although circumcision sig-
nificantly reduces the risk. In childhood and into
adulthood, girls are at a much higher risk than boys,
and the incidence in girls rises steadily by approxi-
mately 1% per decade of life, reaching 10% in fe-
males up to 65 years old. As many as 50% of women
report having had at least one UTI in their lifetimes.
Urinary tract infection is a special problem in the
elderly population, both for men and women. The
incidence of complicated UTI is higher because of a
higher prevalence of urinary tract abnormalities,
245
Urinary Tract Infection
such as prostatic hypertrophy, neurogenic bladder,
and insertion of urethral catheters. Urinary tract
infection is the most common source of bacteremia
in elderly people. 3 Not surprisingly, UTI is the most
common cause of infection in nursing home resi-
dents. 4 In a recent study of 1,754 residents of 13
California nursing homes, UTI had an attack rate
of 16% and accounted for 34.2% of total infection
during the 6-month study period. As the population
ages, the problem of UTI will continue to grow; 22%
of persons aged 85 years or older now reside in nurs-
ing homes.
In addition to age, there are several other well-
defined risk factors for acquiring infections of the
urinary tract. In a prospective study of sexually ac-
tive young women at a university health center and
at a health maintenance organization, increased risk
of UTI was associated with recent use of a dia-
phragm with spermicide, recent sexual intercourse,
and a history of recurrent UTI. 5 In the university
cohort (mean age, 23 years old), the incidence of in-
fection per person-year was 0.7, and the incidence
in the health maintenance organization cohort
(mean age, 29 years old) was 0.5. The association of
UTI with the use of a spermicide has been confirmed
in several studies and is most likely caused by a
change in the vaginal flora, allowing enhanced vagi-
nal and urethral colonization by uropathogens. 6
Recurrence of UTI also is common after the first
infection. In a prospective study of 179 women with
cystitis caused by E coli, 44% had at least one recur-
rence of infection in 12 months. 7 During the I-year
follow-up period, 33% of the recurrent infections
were caused by a serologically identical strain of E
coli as in the index UTI. Therefore, although most
UTI recurrences are caused by reinfection with a
new strain, persistence of the infecting organism
after appropriate treatment or reinfection with the
same strain occurs in a significant number of pa-
tients.
Microbiology
The majority of uncomplicated UTIs are caused by
uropathogenic strains of E coli; as many as 90% of all
UTIs are caused by this single organism. s However,
other Enterobacteriaceae, such as Klebsiella, Entero-
bacter, and Proteus, also are common uropathogens,
as is Pseudomonas. Gram-positive bacteria, such as
S saprophyticus and Enterococcus, can produce in-
fection in certain circumstances. S saprophytic us
causes approximately 10% ofUTIs in young women,
particularly in the summer and fall. Enterococcus
often is a problem in complicated UTI, in patients
with indwelling urethral catheters, or in patients
receiving broad-spectrum antibiotics for another in-
fection. Often, an isolate of Enterococcus in the urine
is a signal that mixed infections or urinary disease
may be present. 9 In contrast to primary UTI, S
246
aureus is the most common bacterium that infects
the urinary tract from a secondary source, often the
bloodstream.
Complicated UTI is more likely to be caused by
unusual or drug-resistant organisms. A variety of
bacteria, mycobacteria, viruses, and yeast have been
isolated from the urinary tract. Nocardia astero-
ides/o Oligella (previously Moraxella) urethralis,l1
Actinomyces bernardiae (previously Centers for Dis-
ease Control and Prevention fermentative corynef-
orm group 2)12 and Mycobacterium terrae complex I3
UTIs all have been reported recently in patients with
structural abnormalities of the urinary tract. Occa-
sionally, other enteric pathogens, such as nonty-
phoidal Salmonella can cause UTI, often in the set-
ting of immunosuppression or occult structural ab-
normalities. 14 A case report of UTI caused by a strain
of Enterococcus faecalis dependent on vancomycin
for growthI5 emphasizes the problems of increasing
proliferation of drug-resistant organisms and persis-
tent, complicated UTI caused by indwelling urethral
catheters.
The microbiologic spectrum of bacteremia origi-
nating from a urinary tract source reflects the spec-
trum of agents that causes primary UTI. In a case
study of 180 adults (101 of whom were older than
65 years) with bacteremic UTIs in a community hos-
pital, 80% of the infections were with gram-negative
organisms; the majority was E coli. 3 Patients with
long-term indwelling urethral catheters had more
gram-positive infections (32% versus 14% of patients
without catheters) and non-E coli gram-negative in-
fections (35% versus 14% of patients without cathe-
ters). In this study and others, advanced age was
not an independent risk factor for mortality.
Candida fungemia, which originates from the uri-
nary tract, also occurs. I6 In one series of patients
with Candida fungemia from a urinary source from
the Mayo Clinic in 1993, 19% of the patients were
infected with Torulopsis glabrata, a species resistant
to fluconazole. I6 As the use of fluconazole continues
to increase, resistant Candida species are predicted
to become increasingly important.
Pathophysiology
The pathophysiology of UTI is a complex interac-
tion between virulence factors of microorganisms
and host defenses. Although virulence factors have
been characterized best in E coli, many of the same
principles may be applicable to Klebsiella and other
gram-negative bacteria.17
Most isolates of uropathogenic E coli belong to a
specific number of O:K:H serotypes and possess ad-
hesion organelles called fimbriae. IS Specifically, P
fimbriae mediate attachment of E coli to uroepithel-
ial cells; therefore, bacterial strains with P fimbriae
are found most often in acute pyelonephritis (90%)
but in relatively few cases of asymptomatic bacteri-
October 1997 Volume 314 Number 4

uria (30%). Additionally, children with intestinal
carriage of E coli with P fimbriae are at a greater risk
of developing UTI. 19 Recently, the specific receptor20
and the possible role of type 1 fimbriae in UTI has
been shown. 21 Type 1 fimbriae increase the virulence
of E coli by promoting bacterial persistence in the
bladder, as well as in the upper tract, and by enhanc-
ing the inflammatory response of the host. Type 1
fimbriae probably act with P fimbriae to cause dis-
ease.
In addition to fimbriae, the aerobactin-mediated
uptake of iron may promote bacterial growth in uri-
nary tissues, but this association with clinical UTI
is less clear. Hemolysin also may contribute to host-
cell injury by its cytotoxic effect, especially in men
with acute pyelonephritis. 22 However, its full mecha-
nism and association with clinical disease is uncer-
tain. Many of the virulence factors, such as P fim-
briae and hemolysin-distinguishing uropathogenic
strains of E coli, are found together on "pathogenic-
ity islands," which are large 35 kb to 190 kb seg-
ments of DNA that apparently have been acquired
by horizontal gene transfer. 23
Several host factors also playa role in the develop-
ment of UTI. In healthy young women, behavioral
factors, such as sexual activity, spermicide use, and
voiding practices, can contribute to urethral coloni-
zation with uropathogens and ultimately lead to in-
fection. A temporal association between UTI and the
stage of the menstrual cycle has been observed,24
most often in the second week of the cycle. It is not
clear if this association reflects the variations in sex-
ual activity or the effects of estrogen. Finally, an
increased frequency of Lewis blood-group nonse-
cretor, Le(a+b-), and recessive, Le(a-b-), phenotypes
have been observed in women with recurrent UTI. 25
This finding may relate to the binding ability ofbac-
teria to uroepithelial cells in these women.
In contrast to young women, elderly people have
different host factors associated with UTI. Specifi-
cally, the use of urethral catheters may thwart host
defenses and predispose patients to UTI. 26 The cath-
eter enhances uropathogenic colonization and may
mechanically damage the adjacent epithelium. The
incidence of bacteriuria is 3% to 10% per day of in-
dwelling urethral catheterization. External, or con-
dom, catheters also are associated with UTI in
men. 27 In addition to urethral catheters, a number
of other factors complicate UTI in elderly people:
prostatic hypertrophy, concomitant medical ill-
nesses, neurogenic bladder, and, most importantly,
nosocomial acquisition of infection.
Clinical Manifestations
Symptoms of acute UTI include dysuria and in-
creased frequency of voiding. Urine often is cloudy
and sometimes contains blood. Fever (> 38° C) is
not characteristic of uncomplicated acute cystitis,
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Barnett and Stephens
however, acute pyelonephritis may manifest with
high fever and costovertebral pain. Physical exami-
nation may show suprapubic tenderness in cystitis,
but often, results are normal. A bulging flank mass
may be present in patients with perinephric ab-
scess. 28
Few if any of the classic symptoms and signs of
UTI may manifest in elderly patients. They are more
likely than younger patients to have gastrointestinal
symptoms, such as nausea and vomiting. Older pa-
tients often do not have fever with pyelonephritis or
urosepsis. Decreased urinary output may be a sign
of bacteremia or of an obstructed indwelling urinary
catheter.
Quantitative bacterial counts greater than 105 col-
ony forming units/mL traditionally have been used
as clinical markers for significant bacteriuria; colony
counts less than 105 colony forming units/mL were
considered to be contaminants from nearby struc-
tures. This cut off limit has been used in clinical
trials and other investigations, but its clinical rele-
vance recently has been reassessed. 29 Kunin et al 29
reported that "low-count" bacteriuria, defined as 102
colony forming units/mL to 104 colony forming units/
mL, was statistically more frequent in women with
urinary complaints than in asymptomatic women.
They suggest that, in patients with low bacterial
colony counts, infection has not been established in
the bladder but rather is an early phase of UTI and
should be treated if the patient is symptomatic and
if pyuria is present. The term "urethral syndrome"
has been used to refer to a symptom in patients with
dysuria and for counts less than 105 bacterial colony
forming units/mL in a urine sample. In addition to
UTI, other causes of acute urethral syndrome are
urethritis because of Chlamydia trachoma tis and
Neisseria gonorrhoeae infection, genital herpes in-
fection, vaginitis, and noninfection factors such as
psychologic or allergic causes.
Asymptomatic bacteriuria in elderly patients is a
special circumstance that usually does not necessi-
tate treatment. At any particular time in a nursing
home population, approximately 25% of women and
20% of men have significant bacteriuria; of the el-
derly patients who are not in nursing homes, approx-
imately 20% of women and 5% of men have bacteri-
uria. 30 Treatment with antibiotics in these patients
has no benefit in morbidity or mortality.31 Further-
more, treatment of asymptomatic patients may lead
to future infection with resistant microorganisms
and to side effects caused by antibiotics. An excep-
tion is the finding of Proteus or other urea-splitting
bacteria in the urine. Patients with these should be
treated because ofthe organisms' propensity to form
urinary stones. 32
Diagnosis
A presumptive diagnosis of UTI can be made
based on the presence of increased frequency of uri-
247
Urinary Tract Infection
nation, dysuria, bloody or cloudy urine, suprapubic
tenderness, fever, or costovertebral pain. A definite
diagnosis depends on the demonstration of pyuria
and bacteriuria.
The urine dipstick test can rapidly check voided
urine for pyuria and bacteriuria by detection of leu-
kocyte esterase and nitrite, respectively. The leuko-
cyte esterase test detects pyuria (> 10 leukocytes/
mL to 20 leukocytes/mL) and indicates inflamma-
tion, but not specifically bacterial infection. 33 Gener-
ally, it is predictive enough to administer empiric
antibiotics. For symptomatic patients with a nega-
tive leukocyte esterase, microscopic evaluation of an
unspun urine sample to look for leukocytes is appro-
priate. The urine nitrite dipstick test is highly spe-
cific for bacteria but relatively insensitive. 8 A gram
stain of urine is important for early etiologic assess-
ment.
In the elderly population and in nursing home res-
idents, special care must be taken in evaluating a
urine dipstick test. 34 In conjunction with the acute
onset of urinary tract symptoms, positive results of
leukocyte esterase and positive nitrite indicate a
high probability for UTI. However, in the absence of
acute onset of such symptoms, the results of a posi-
tive leukocyte esterase or nitrite reaction should be
investigated using urine cultures. Many older adults
have asymptomatic bacteriuria, therefore, the find-
ing of bacteriuria without pyuria should not preclude
a search for alternative sources of infection in a fe-
brile elderly patient; lower UTI alone rarely causes
fever.
Urine specimens for culture can be collected by
a clean-void method in most acutely symptomatic
women or from the catheter in a patient with an
indwelling urethral catheter. The etiologic organism
is virtually always accompanied by pyuria if true
infection is present. In a few patients, urinary cathe-
terization may be needed to provide uncontaminated
urine, but there is a small risk of infection with the
introduced catheter.35
Treatment
The treatment of urinary tract infection was the
subject of an outstanding recent review by Stamm
and Hooten. 36 They organized patients with UTI into
five groups: 1) young women with acute uncompli-
cated cystitis, 2) young women with recurrent cysti-
tis, 3) young women with acute uncomplicated pyelo-
nephritis, 4) all adults with complicated UTI, and 5)
all adults with asymptomatic bacteriuria. Empiric
antibiotics and duration of therapy depends on the
classification of the patient into one of these groups.
For acutely symptomatic young women with cysti-
tis, an abbreviated laboratory workup (test for py-
uria without a culture) and a 3-day course of empiric
antibiotics, such as trimethoprim-sulfamethoxazole
or a fluoroquinolone, which eradicate E coli, S sapro-
248
phyticus, Proteus mirabilis, and Klebsiella pneumon-
iae are recommended. 36 For patients with diabetes
mellitus, a recent history of UTI, or who are older
than 65 years, a 7- to 14-day course of antibiotics
may be more appropriate. For recurrent cystitis
(more than two UTIs per year) in young women,
treatment with continuous or postcoital prophylaxis
may be appropriate. In certain patients with less
frequent recurrences, patient-initiated therapy is an
option. 36 In postmenopausal women, intravaginal es-
triol significantly reduces the incidence of recurrent
UTI. 37
In acute uncomplicated pyelonephritis in young
women, oral therapy with a fluoroquinolone or tri-
methoprim-sulfamethoxazole for 14 days is recom-
mended. A urine culture is indicated in all cases
of suspected pyelonephritis. Admission to a hospital
and parenteral antibiotics may be necessary if the
patient is nauseated or vomiting, has otherwise toxic
symptoms, or has an underlying illness (eg, diabetes
mellitus). Cultures of the urine and blood should be
obtained in this setting. If the gram stain indicates
possible infection with Enterococcus, ampicillin and
gentamicin should be used; otherwise a fluoroquino-
lone, an extended-spectrum penicillin with a ,B-Iacta-
mase inhibitor, or a third-generation cephalosporin
are adequate. 36 If fever and flank pain persist for
more than 72 hours, diagnostic imaging with ultra-
sonography or computed tomography is indicated.
For patients with complicated UTI, therapy often
must be guided by the results of urine cultures to
obtain the etiologic organism and antibiotic sensitiv-
ities. In selecting empiric antibiotics, coverage
against Enterococcus and Pseudomonas should be
provided. Recurrences often will occur ifthe underly-
ing complication (either structural or functional)
cannot be corrected.
Screening for asymptomatic bacteriuria is recom-
mended during pregnancy and before urologic sur-
gery, two times at which treatment has been shown
to be beneficial. The treatment of UTI during preg-
nancy will reduce the risk of acute pyelonephritis
and prematurity in the newborn. Treatment of
asymptomatic bacteriuria in elderly people usually
is not recommended. The exception may be in women
who have asymptomatic bacteriuria in the presence
of urinary catheters in whom treatment with antibi-
otics, for complicated UTI, for example, may be indi-
cated. 38
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