The Woman with Dysuria

The Woman with Dysuria
KURT KUROWSKI, M.D.,
Finch University of Health Sciences/Chicago Medical School
North Chicago, Illinois
Bacterial cystitis is the most common bacterial infection occurring in women. Thirty
percent of women will experience at least one episode of cystitis during their lifetime.
About one third of patients presenting with symptoms of cystitis have upper urinary
tract infections. A careful history to identify risk factors for subclinical pyelonephritis
is important. Symptoms of chronic cystitis accompanied by sterile urine without
pyuria may represent interstitial cystitis. Dysuria may also be the principal complaint
of women with vaginitis (infectious, atrophic or chemical) or urethritis. A stepwise
diagnostic approach, accompanied by inexpensive office laboratory testing, is usually
sufficient to determine the cause of dysuria.
An appropriate starting point in identifying the cause of dysuria is to attempt to
classify the woman's symptoms by the specific anatomic site thought to be
responsible. Table 1 lists disorders associated with symptoms of dysuria and their
characteristic laboratory and physical findings.
TABLE 1
Differential Diagnosis of Women with Dysuria
Diagnosis
Cystitis
Associated
symptoms
Additional
history
Physical
examination
Laboratory
and other
test results
Frequency,
urgency, may
have gross
hematuria
Recent
sexual
intercourse,
risk factors
present (see
Table 2)
15 to 20% have
suprapubic
tenderness; no
costovertebral
angle tenderness
Usually
positive for
pyuria and
sometimes
also positive
for bacteriuria
and nitrite
Frequency,
Subclinical
urgency, may
pyelonephritis have gross
hematuria
Usually
positive for
pyuria and
sometimes
also positive
for bacteriuria
May have
and nitrite;
Risk factors suprapubic
positive renal
present (see tenderness; no
cortical
Table 5)
costovertebral
scintigraphy,
angle tenderness
urine culture
usually > 105
colonyforming units
per mL of
urine
Nausea,
emesis, fever,
Acute
sepsis,
pyelonephritis
back/flank
pain
Interstitial
cystitis
May have
had
concurrent
or preceding
cystitis
symptoms
(see Table 5)
Often
middleFrequency,
aged;
urgency, gross longstanding
hematuria
symptoms
(20%)
with
negative
cultures
Costovertebral
angle tenderness,
deep right or left
upper quadrant
tenderness
Pyuria usually
present with
casts of white
blood cells;
obtain urine
culture and
sensitivity
Urinalysis
negative for
No costovertebral
white blood
angle tenderness;
cells or
may have
bacteria;
suprapubic
positive for
tenderness
glomerulations
on cystoscopy
Vaginitis
External
irritation,
vaginal
discharge or
pruritus,
dyspareunia;
no hematuria
Premenstrual
exaggeration
of
symptoms;
sexual
activity or
recent
antibiotic
exposure or
postmenopausal
and not
receiving
estrogen
replacement
therapy
Vaginal
discharge,
inflamed vaginal
mucosa (absent
in bacterial
vaginosis),
inflamed cervix
(Trichomonas),
vaginal atrophy
(postmenopausal)
Genital
herpes
Dysuria, fever,
headache,
myalgias, neck
pain, vulvar
pain,
photophobia
Sexually
active; may
have vaginal
discharge
Grouped vesicles
usually on cervix
or pubic area, but Viral culture
may be vaginal; optional
tender inguinal
adenopathy
Urethritis
Usually
asymptomatic;
if symptoms
develop, they
are usually
delayed (>1
week)
History of
unprotected
sexual
exposure
No suprapubic
pain unless
associated with
pelvic
inflammatory
disease; rarely,
visible urethral
discharge
Positive
potassium
hydroxide or
vaginal saline
preparation
elevated pH
(bacterial
vaginosis or
Trichomonas)
Urethral swab
positive for
white blood
cells; obtain
Gram stain to
detect
intracellular
gram-negative
diplococci and
DNA probe for
Chlamydia
and gonorrhea
Historical Differentiation
Dysuria with frequency and urgency suggests cystitis.1 Women usually sense
internal discomfort (located in the urethra and bladder) as opposed to external
discomfort such as the labial irritation associated with vaginitis. Hematuria is
common with urinary tract infections and is unlikely to occur with other potential
etiologies.1 Sexual intercourse is associated with many causes of dysuria, but
women with postcoital cystitis typically develop symptoms within a few days of
intercourse, whereas women with urethritis develop symptoms one to two weeks
later and women with vaginitis develop symptoms from weeks to months later. A
history of recurrent urinary tract infections, use of a spermicide and diaphragm, and
a higher frequency of intercourse within the previous week increases the risk for a
urinary tract infection.2 Only about 15 to 20 percent of women with acute cystitis
have suprapubic pain.1 Rarely, women with cystitis mention lower back pain or have
a low-grade fever.
Associated vaginal discharge suggests some type of vaginitis, although patients with
urethritis can atypically have a discharge as well. Perimenstrual exacerbation of
symptoms points to candidal or Trichomonas vaginitis. Dyspareunia and the
sensation of the dysuria being external are typical of vaginitis. Dysuria associated
with symptoms of pelvic inflammatory disease, occurring about one to two weeks
after intercourse or noted just at the start of urination, suggests urethritis.3
Associated fever, myalgia and headache suggest acute pyelonephritis or primary
genital herpes as the cause of dysuria. Nausea and emesis also typically accompany
acute pyelonephritis. Bladder irritation from a distal urethral stone, compression
from an adnexal mass, and radiation or chemical exposure can also produce dysuria.
Examination Differentiation
The physical examination is unremarkable in patients with cystitis, except in the 15
to 20 percent of patients who have suprapubic tenderness. Fever (greater than
38.5°C [101.3°F]), costovertebral angle tenderness or upper abdominal tenderness
to deep palpation suggest acute pyelonephritis. Women with candidal or Trichomonas
vaginitis may have vaginal discharge. Satellite vaginal pustules are sometimes
present in patients with vaginal candidiasis, and grouped painful vesicles and tender
inguinal adenopathy may be present in patients with genital herpes.
Laboratory Differentiation
If symptoms of cystitis are present, the finding of more
than 102 colony-forming units per mL indicates true
infection.
Urine Analysis
The most sensitive laboratory indicator for urinary tract infections is pyuria. A
positive leukocyte esterase dipstick test is 75 to 95 percent sensitive in detecting
pyuria secondary to infection.4 If no vaginal contamination occurs during collection,
vaginitis does not produce pyuria. The presence of white blood cell casts suggests
acute pyelonephritis. Bacteriuria and urine nitrite are also frequently present but are
less sensitive indicators of urinary tract infection. Most of the subtypes of the known
bacterial pathogens (with the exception of Staphylococcus saprophyticus and
Enterococcus) can convert urinary nitrate to nitrite. Positive nitrite is over 90 percent
specific for urinary tract infections, but sensitivity is usually only about 30 percent.5
This is secondary to the six-hour incubation time needed. Sensitivity increases to 60
percent with first-voided morning urine samples.
Urine Culture
Women with uncomplicated cystitis who are not pregnant do not usually require a
urine culture. However, if a culture is performed and symptoms of cystitis are
present, the finding of greater than 102 colony-forming units per mL of urine in a
promptly cultured specimen is significant.
Vaginal Smears/pH Testing
Increased vaginal pH is characteristic of trichomoniasis and bacterial vaginosis;
however, bacterial vaginosis does not typically produce dysuria. The replacement of
vaginal lactobacillus with coliform bacteria also increases pH. This may occur in
women with recurrent urinary tract infections. Potassium hydroxide and normal
saline vaginal smears may reveal mycelia and motile trichomonads in patients with
suspected vaginitis. Most women with urethritis are found to have greater than five
white blood cells per high-power field on urethral smear.
Cystitis
Acute cystitis is the most common bacterial infection occurring in women. Of the
more than 30 percent of women who will experience at least one episode of cystitis
in their lifetime, 20 percent will have recurrent cystitis.3
Pathogenesis. The shorter urethra in women makes the ascension of bacteria more
likely, especially during sexual intercourse. Urine is a natural bactericide with a low
pH and a high osmolarity and urea content. Normal urine flow and voiding physically
expel bacteria from the urinary tract. A protective mucin coating also inhibits the
adherence of bacteria. Women normally have lactobacillus colonization of the vaginal
mucosa. Vaginal secretions have a lower pH that inhibits coliform bacteria.
TABLE 2
Conditions That Cause an Increased Incidence of Urinary
Tract Infections in Women
Condition
Cause
Obstruction or
alterations in
urine flow
Tumors or stones in ureter or at
ureterovesical junction; anomalies of tract
anatomy/function such as cystocele, cystic
kidneys, pregnancy
Alterations in
normal vaginal
lactobacillus
colonization
Nonoxynol-9 in spermatocidal jellies
selectively kills lactobacillus but not
Escherichia coli2; certain antibiotics
(especially beta-lactambased) alter vaginal
flora; postmenopausal status is associated
with a decrease in vaginal lactobacillus
colonization1
Disruption of
mucin layer
Urinary tract instrumentation, including
insertion of Foley catheter
Some patients experience the disruption of some of these defense mechanisms. The
conditions that increase the incidence of disruptions are listed in Table 2. Some
women have genetically determined receptors on their uroepithelial cells that allow
attachment by the glycolipid fimbriae of many fimbriated subtypes of bacteria.
Women with these receptors who do not have mucosal secretion of a
fucosyltransferase enzyme (which helps to block bacterial adherence) are more likely
to have the lactobacillus in their vaginal mucosa replaced with Escherichia coli and
other coliforms from their rectum and to have more frequent episodes of cystitis.
Since these uroepithelial receptors are also found in the upper urinary tract, these
women are also more prone to pyelonephritis.6,7 Table 3 lists the likely bacterial
pathogens in uncomplicated and complicated urinary tract infections.
TABLE 3
Incidence of Bacterial Pathogens in Lower Urinary Tract
Infections
Pathogen
Uncomplicated infections
Escherichia coli
Staphylococcus saprophyticus
Proteus mirabilis
Klebsiella pneumoniae
Enterobacter species
Beta-hemolytic streptococci
Complicated infections
E. coli
Enterococcus faecalis
P. mirabilis
Staphylococcus epidermidis
K. pneumoniae
Pseudomonas aeruginosa
Staphylococcus aureus
Enterobacter species
Others*
Incidence (%)
80
10
5
4
1
<1
35
16
13
12
7
5
4
3
5
*--Includes Serratia, Streptococcus, Acinetobacter and
Citrobacter species.
Adapted with permission from Sweet RL, Gibbs RS. Infectious
diseases of the female genital tract. 3d ed. Baltimore: Williams
& Wilkins, 1995.
Treatment. Many episodes of bacterial cystitis resolve without treatment. The
consumption of cranberry juice decreases the ability of the bacteria to attach to
uroepithelial cells.8 Antibiotics hasten the resolution of symptoms and prevent the
infection from spreading into the upper urinary tract. Adult nongravida women with
uncomplicated cystitis may be treated empirically with a three-day course of
antibiotics based on their clinical presentation and evidence of pyuria. Urine culture
is not necessary in these women but should be performed if there is no pyuria
despite a clinical picture of cystitis.
Many antibiotics are effective in the treatment of cystitis, and most achieve high
concentrations in the urine. Selection of the antibiotic should be determined by side
effect profiles, drug interactions, cost and teratogenic effects. Drugs and dosages for
antibiotic therapy for uncomplicated cystitis in women are listed in Table 4. Although
fluroquinolones have been proved to be effective for the treatment of uncomplicated
cystitis, their use should be avoided because of cost and potential teratogenic
effects. About 30 percent of the bacteria that cause cystitis are currently resistant to
amoxicillin or sulfamethoxazole. Only 15 to 20 percent of bacteria are resistant to
nitrofurantoin (Macrobid, Macrodantin), and 10 to 15 percent are resistant to
trimethoprim (Trimpex) or trimethoprim-sulfamethoxazole (Bactrim, Septra).
Recurrent infections are usually reinfections separated by an asymptomatic interval
of at least one month's duration. They are usually caused by vaginal and rectal
colonization with uropathogens. Anatomic abnormalities in young women with
recurrent cystitis are rare.9 The diffusion of trimethoprim into vaginal fluid to clear
vaginal colonization of uropathogens is a key factor in its success in shorter-course
therapy.10
Complicated Urinary Tract Infections. Complicated urinary tract infections are defined
as those occurring in patients with anatomically or functionally abnormal urinary
tracts, or in patients who are immunocompromised or have iatrogenic infections.
Clinical recognition of complicated urinary tract infections is important because these
patients are more likely to harbor resistant organisms (Table 3). Therapy consists of
broader spectrum agents such as fluroquinolones. Cystitis should be treated for one
week. Upper urinary tract infections should be treated for two weeks. A urine culture
should be obtained to confirm sensitivity.
TABLE 4
Empiric Oral Antibiotic Therapy for Uncomplicated
Cystitis in Women
Drug
Dosage
Trimethoprimsulfamethoxazole (Bactrim
DS, Septra DS)
One double-strength (160
mg/800 mg) tablet taken orally
twice daily for three days
Trimethoprim (Trimpex)
One 100-mg tablet taken orally
twice daily for three days
Nitrofurantoin (Macrobid,
Macrodantin)
One 100-mg tablet taken orally
four times daily for three days
NOTE: Sulfamethoxazole is contraindicated in pregnant women
near term. Sulfamethoxazole and nitrofurantoin are
contraindicated in patients with glucose-6-phosphate
dehydrogenase deficiency. Trimethoprim is contraindicated in
patients with folate deficiency. Nitrofurantoin has not been
proved as effective as trimethoprim-sulfamethoxazole or
trimethoprim in three-day clinical trials.
Subclinical Pyelonephritis
Appropriately named, subclinical pyelonephritis represents a diagnostic challenge to
clinicians, because although patients with the condition have renal parenchymal
involvement, they experience only the symptoms of cystitis.11 Estimates based on
bladder washout studies show that 30 percent of women presenting with symptoms
of cystitis actually have subclinical pyelonephritis.12 This finding has important
therapeutic sequelae: infections are more difficult to eradicate and require a twoweek course of antibiotic therapy compared with the usual three-day course for
cystitis,13,14 and since the renal parenchyma is involved, organism identification
and confirmation of sensitivity are important.
Subclinical pyelonephritis is distinguished from cystitis
on the basis of risk factors and requires treatment with a
two-week course of a broad-spectrum antibiotic.
A urine culture and sensitivity should be obtained when an upper urinary tract
infection is suspected based on clinical symptoms or risk factors. Table 5 lists the
identifiable factors that increase a patient's risk for subclinical pyelonephritis. The
clinician must suspect subclinical pyelonephritis in any patient with symptoms of
cystitis who has one or more of the risk factors listed in Table 5. The physician
should be aware that complicated urinary tract infections and subclinical
pyelonephritis are not mutually exclusive and have overlapping risk factors. Patients
with symptoms of cystitis and one or more risk factors for subclinical pyelonephritis
should be treated for both conditions with empiric broader-spectrum antibiotics for
two weeks.
Most patients with subclinical pyelonephritis tend to have bacterial counts greater
than 105 units per mL on quantitative culture, but the specificity of this culture is not
high enough to be clinically useful. Many laboratory tests, such as the antibodycoated bacteria assay and erythrocyte sedimentation rates, have been used to help
identify patients with subclinical pyelonephritis, but the specificity of these tests is
too poor to make them clinically useful. Renal cortical scintigraphy has an 86 percent
accuracy rate in distinguishing upper tract infections.15 Patients with upper tract
involvement will show a focal asymmetric uptake. Treatment, however, is usually
based on the presence of risk factors and is usually determined without using
imaging studies.
TABLE 5
Risk Factors for Subclinical Pyelonephritis in Women
Symptoms present for more than one week before seeking
treatment
Diabetes mellitus
Immunocompromised
Pregnancy
Anatomic anomaly of the urinary tract
Vesicoureteral reflux
Relapse of symptoms within three days of treatment for acute
cystitis
Ureteral obstruction
History of acute pyelonephritis within one year
Adapted with permission from Johnson CC. Definitions,
classification and clinical presentation of urinary tract infection.
Med Clin North Am 1991; 75:241-52.
Interstitial Cystitis
Interstitial cystitis is an inflammatory condition of the bladder of unknown etiology.
It is much more common than was previously believed, affecting an estimated
450,000 persons in the United States.16 Ninety percent of affected patients are
women. Some experts believe that men with prostatodynia, especially those with
symptoms of cystitis, may actually have interstitial cystitis.17 Adding these men to
the number of affected patients decreases the female predominance.
Epidemiologic studies have shown that patients with interstitial cystitis have had
their symptoms for an average of 4.5 years before they are correctly diagnosed, and
that the median age of afflicted patients is 40 years (about one quarter of these
patients are less than 30 years old) at the time of diagnosis. No clear genetic
predisposition has been proved, but studies have revealed that about 15 percent of
patients are of Jewish origin.18 Patients with interstitial cystitis are more likely to
have had urinary tract infections both as adults and as children.
The etiology of interstitial cystitis remains unclear. Many efforts have been made,
without success, to culture a causative organism. In past decades, this disorder was
considered to be a manifestation of an underlying psychiatric disorder and, indeed,
many patients with this condition reported feelings of depression and anxiety, and a
history of psychiatric care.18 Most authorities now believe that, at least in most
patients, these feelings represent an understandable response to their disorder and
are not the cause of it. Theories abound as to the true cause of interstitial cystitis.
Presently, the most popular theory is that alterations occur in the glycosaminoglycan
mucous layer, possibly in response to a previous bacterial urinary tract infection,
allowing solutes in the urine to provoke a secondary inflammatory response.19
Diagnostic Evaluation
Interstitial cystitis may be treated initially with an oral
agent; however, intravesical or surgical therapy may
eventually be necessary to control symptoms
Interstitial cystitis remains a diagnosis of exclusion. Patients present with dysuria,
urgency and frequency (some affected patients urinate from 60 to 80 times a day
and from 10 to 30 times at night). The majority of patients have dyspareunia, and
about 20 percent of patients have gross hematuria. Characteristic symptoms of
interstitial cystitis are listed in Table 6. Patients who have this condition will have
these symptoms along with evidence of Hunner's ulcers (mucosal ulcerations on the
bladder wall with surrounding granulation tissue) or glomerulations (multiple
petechial-like hemorrhages seen in the bladder mucosa with the bladder distended
during cystoscopic examination). Most authorities recommend beginning the physical
evaluation with a urodynamic study to demonstrate a reduced bladder capacity.
Bladder biopsies may also be taken to rule out other potential etiologies such as
carcinoma in situ.
TABLE 6
Symptom Characteristics of the Patient with Interstitial
Cystitis
Symptoms of suprapubic pain with nocturia and frequency of at
least eight times a day for at least nine months
Patient older than 18 years of age
Bladder capacity of less than 350 mL and urge to void if
distended with 150 mL of urine
No recent (within the last three months) diagnosis of bacterial
cystitis or prostatitis
No alternative explanation for the patient's symptoms (e.g.,
tuberculous cystitis, radiation cystitis, tumors of the
genitourinary tract, chemical cystitis or active genital herpes or
vaginitis)
Adapted with permission from Hanno PM. Diagnosis of
interstitial cystitis. Urol Clin North Am 1994;21(1):63-6.
Treatment
There is no known curative therapy for interstitial cystitis; consequently, efforts are
directed at ameliorating symptoms and improving function. Patients usually begin
with oral therapy and, if it is not successful, are changed to intravesical therapy.
Transcutaneous electrical nerve stimulation (TENS) is effective in some patients.20
Patient response to any oral therapeutic agent is usually modest at best. While these
agents have been shown to improve patients' symptoms relative to placebo,
evidence from large double-blind, controlled studies is lacking. Pentosan polysulfate
(Elmiron) was recently labeled by the U.S. Food and Drug Administration (FDA) as an
oral therapy for interstitial cystitis. It is a heparin-like compound with anticoagulant
and fibrinolytic effects. Its mechanism in interstitial cystitis is unknown; however, it
has been postulated that it acts by augmenting the glycosaminoglycan mucous
protective lining of the bladder wall. Given these serious limitations, the oral
therapies most commonly prescribed appear in Table 7.
Intravesical therapies include hydrodistention of the bladder during cystoscopic
evaluation. This is believed to be therapeutic secondary to the ischemia produced to
the submucosal nerve plexuses and stretch receptors. About 20 percent of patients
report decreased pain and increased bladder capacity after this procedure, but
unfortunately symptoms usually recur within three months.
Intravesical dimethyl sulfoxide (DMSO; Rimso-50) has anti-inflammatory and
analgesic properties and is the only intravesical agent labeled by the FDA for the
treatment of interstitial cystitis. The patient's urine must be sterile and at least one
month must have passed since any bladder biopsies have been taken. Patients often
complain of a transient worsening of their symptoms due to the chemical cystitis
produced in the first day or two after treatment and will also notice a garlic-like odor
to their breath, but 50 to 70 percent of patients with classic interstitial cystitis and
50 to 90 percent of patients with nonulcer interstitial cystitis obtain significant relief
from this treatment.22,23 Even though about 40 percent of treated patients relapse,
they usually improve again after another instillation.23 Patients who do not respond
to dimethyl sulfoxide alone should undergo a second course of treatment that
includes 100 mg of hydrocortisone.
Surgery should be reserved for use in severe cases that are refractory to medical
treatment. The most common surgical procedure performed is a supratrigonal
cystectomy with formation of an enterovesical anastomosis. In this procedure, a
small cuff of residual bladder around the trigone is anastomosed to a portion of
bowel segment. This procedure is effective in 60 to 90 percent of patients.24 It is
more likely to be effective in patients with smaller bladder capacities (less than 400
mL).25
Patients with interstitial cystitis report great disability from their symptoms. About 50
percent of patients state that they are unable to work full time. Patients with
interstitial cystitis score lower on self-assessment quality-of-life scales than do renal
dialysis patients. Physicians or patients seeking more information about this
condition can contact the following organization: The Interstitial Cystitis Association,
P.O. Box 1553, Madison Square Station, New York, NY 10159-1553; telephone: 212979-6057; 800-HELP-ICA (800-435-7422).
TABLE 7
Oral Therapy for Interstitial Cystitis
Oral agent
Dosage
Pentosan
polysulfate
300 mg per day
Amitriptyline
(Elavil)
Starting at 25 mg per day at bedtime,
increasing by 25 mg every two to four
weeks up to 150 mg per day at bedtime
Hydroxyzine
(Atarax)
25 to 50 mg per day at bedtime
Nifedipine
(Adalat,
Procardia)
30 mg (extended-release) every day,
increasing to 60 mg per day in one month
Cimetidine
(Tagamet)21
200 mg three times per day
*--Pentosan polysulfate is the only oral agent labeled by the
U.S. Food and Drug Administration for the treatment of
interstitial cystitis. Limited evidence supports the efficacy of the
other agents in the treatment of this condition.
Vaginitis
When vaginitis causes a concomitant dysuria, the symptoms and physical findings
usually are sufficient to make the diagnosis. Candida, Trichomonas and genital
herpes produce dysuria either because of direct injury to the vaginal epithelium or
because of an associated inflammatory response. On the other hand, bacterial
vaginosis and some cases of urethritis are far less likely to cause dysuria because
these infections produce less local inflammation.
Candidal Vaginitis
Dysuria, vaginal pruritus and discharge are the most common symptoms of
candidiasis and usually worsen just before menstruation. Organisms originate in the
perianal area and cause alterations in the normal vaginal environment. The
alterations allow the yeast to multiply, change to its invasive mycelial form and
cause symptoms. Table 8 shows several host factors that increase the risk of
asymptomatic and symptomatic vaginal candidiasis.
TABLE 8
Factors That Increase the Risk for Asymptomatic and
Symptomatic Vaginal Candidiasis
Factor
Mechanism
Pregnancy
Higher vaginal glycogen
content secondary to
increased estrogen and
progesterone levels; estrogen
increases vaginal epithelial
cell adherence by Candida
Contraceptive use (including
high-dose estrogen oral
contraceptive pills, intrauterine
devices, nonoxynol-9,
diaphragm, contraceptive
Elimination of normal
protective flora
sponge)
Antibiotic use
Elimination of normal
protective flora (especially
with the use of tetracyclines
and broader spectrum betalactam antibiotics)
Diabetes mellitus (especially if
poorly controlled)
Increased vaginal glycogen
substrate
Increased association with
sexually transmitted diseases
Increased exposure to
antibiotics and contraceptives
(see contraceptive use
above); possible direct
inoculation of organisms
during intercourse
Tight-fitting, synthetic
underclothing
Increased perineal moisture
and temperature
Corticosteroid therapy
Altered cell-mediated
immunity; increased serum
glucose (see diabetes mellitus
above)
Human immunodeficiency virus Altered cell-mediated
infection
immunity
Trichomonas Vaginitis
Trichomonas vaginalis infection may be asymptomatic but usually causes an
inflammatory vaginitis. There is a three-day to three-week incubation period.
Trichomonads reproduce better at the higher vaginal pH in menstrual blood;
consequently, a woman with Trichomonas vaginitis will usually note that her
symptoms increase during and immediately following menstruation.
Genital Herpes
Eighty percent of patients with primary symptomatic genital herpes will have
dysuria; however, dysuria is usually not present if the infection recurs.26 Most new
cases of genital herpes are acquired from sexual contact with asymptomatic viral
shedders. Primary herpetic infections typically produce dysuria, associated fever,
headache, neck pain, photophobia and tender inguinal adenopathy. Seventy-five
percent of patients with genital herpes will have vaginal discharge.
Atrophic Vaginitis
Dysuria occurs in women with atrophic vaginitis because of urine contact with the
inflamed atrophic tissues themselves or because of the increased incidence of urinary
tract infections in these women. Atrophic vaginitis is a common disorder, affecting
from 20 to 30 percent of postmenopausal women. Decreased vaginal discharge,
vaginal tenderness and dyspareunia are common in women with atrophic vaginitis.
Women may also have bloody vaginal spotting, especially after intercourse.
Atrophic vaginitis also increases the risk for urinary tract infections. Approximately
10 to 15 percent of women over 60 years of age have frequent urinary tract
infections. Postmenopausal status is associated with a higher vaginal pH, a decrease
in vaginal lactobacillus colonization and increased colonization with E. coli. Topical
estriol vaginal cream is an effective treatment in postmenopausal women with
recurrent infections. In one study,27 patients treated with the estriol cream
averaged 0.5 infections per year, compared with about 6.0 infections per year in
women who were not treated.
Infectious Urethritis
Infectious urethritis has not been studied as extensively in women as it has been in
men. Chlamydia infection has long been thought to be responsible for many cases of
dysuria in women with negative urine cultures.28 However, some authorities have
been unable to show an association between dysuria and Chlamydia in women.29 A
correlation between greater than five white blood cells per high-power field on a
urethral swab and the presence of Chlamydia has been identified.29 A gonococcus
may, less commonly, be asymptomatically present in the female urethra as well.
About 75 percent of women with Chlamydia identified on urethral swabs have
simultaneously had the organism isolated from their cervixes. The finding of
intracellular, gram-negative diplococci on Gram's stain is 50 percent sensitive for
gonorrhea infection in women.30 If either organism is suspected, the patient should
undergo further testing such as a DNA probe to confirm the diagnosis.
Miscellaneous
Vaginal and urethral trauma, including sexual abuse and the insertion of a foreign
body, can cause dysuria, as can irritant or topical allergic responses to soaps,
douches, vaginal lubricants, spermicidal jellies, contraceptive foams and sponges,
and tampons and sanitary napkins. Perfumed soaps and toilet paper are also
common causes of dysuria. Avoidance of the irritative agent generally leads to the
resolution of symptoms.
The Author
KURT KUROWSKI, M.D.,
is an assistant professor and predoctoral director in the Department of Family
Medicine at the Finch University of Health Sciences/Chicago Medical School, North
Chicago. He received a medical degree from the University of Wisconsin Medical
School, Madison, and completed a family practice residency at Resurrection Hospital,
Chicago.
Urinary Tract Infections in Adults
ROBERT ORENSTEIN, D.O.
Hunter Holmes McGuire Veterans Affairs Medical Center
Richmond, Virginia
EDWARD S. WONG, M.D.
Virginia Commonwealth University, Medical College of Virginia
Richmond, Virginia
Urinary tract infections remain a significant cause of morbidity in all age groups.
Recent studies have helped to better define the population groups at risk for these
infections, as well as the most cost-effective management strategies. Initially, a
urinary tract infection should be categorized as complicated or uncomplicated.
Further categorization of the infection by clinical syndrome and by host (i.e., acute
cystitis in young women, acute pyelonephritis, catheter-related infection, infection in
men, asymptomatic bacteriuria in the elderly) helps the physician determine the
appropriate diagnostic and management strategies. Uncomplicated urinary tract
infections are caused by a predictable group of susceptible organisms. These
infections can be empirically treated without the need for urine cultures. The most
effective therapy for an uncomplicated infection is a three-day course of
trimethoprim-sulfamethoxazole. Complicated infections are diagnosed by
quantitative urine cultures and require a more prolonged course of therapy.
Asymptomatic bacteriuria rarely requires treatment and is not associated with
increased morbidity in elderly patients.
Urinary tract infections (UTIs) are a leading cause of morbidity and health care
expenditures in persons of all ages. Sexually active young women are
disproportionately affected, but several other populations, including elderly persons
and those undergoing genitourinary instrumentation or catheterization, are also at
risk. An estimated 40 percent of women report having had a UTI at some point in
their lives.1 UTIs are the leading cause of gram-negative bacteremia. In the United
States, these infections account for approximately 7 million office visits and more
than 1 million hospitalizations, for an overall annual cost in excess of $1 billion.1,2
Recently published studies have added to the body of knowledge concerning the
pathogenesis, diagnosis and management of UTIs. However, many practical issues
have yet to be fully addressed. When should urine cultures be obtained? What
diagnostic threshold should be used to define infection? What is the optimal duration
of therapy and how should it be administered? Does bacteriuria in the elderly lead to
adverse outcomes? Should trimethoprim-sulfamethoxazole (Bactrim, Septra) remain
the initial therapy of choice for UTIs? This article clarifies these issues by reviewing
the approach to the diagnosis and treatment of each patient group at risk for UTIs.
In addition, a simple diagnostic approach to urinary tract infection in adults is
presented in Figure 1.
Adult Urinary Tract Infection
FIGURE 1. Diagnostic approach to urinary tract infections in
adults. (UTI=urinary tract infection)
A recent categorization of UTIs is most helpful clinically because it divides patients
into groups based on clinical factors and their impact on morbidity and treatment
(Table 1).3 These categories are as follows: acute uncomplicated cystitis in young
women; recurrent cystitis in young women; acute uncomplicated pyelonephritis in
young women; complicated UTI and its subcategories; UTI related to indwelling
catheters; UTI in men; and asymptomatic bacteriuria.
Acute Uncomplicated Cystitis in Young Women
Those most at risk for UTIs are sexually active young women. Their propensity to
develop UTIs has been explained on the basis of anatomy (especially a short
urethra) and certain behavioral factors, including delays in micturition, sexual
activity, and the use of diaphragms and spermicides (both of which promote
colonization of the periurethral area with coliform bacteria).4 Fortunately, most UTIs
in this population are uncomplicated and are rarely associated with functional or
anatomic abnormalities. In studies of women presenting with dysuria and increased
frequency of urination, intravenous pyelography and ultrasonography have
demonstrated low rates (less than 1 percent) of surgically correctable anatomic
abnormalities of the urinary tract.5 Therefore, aggressive diagnostic work-ups are
unwarranted in young women presenting with an uncomplicated episode of
cystitis.3,6
TABLE 1
Urinary Tract Infections in Adults
Category
Diagnosti Principal
c criteria pathogens
First-line therapy Comments
•
•
Urinalysis
for pyuria
Acute
and
uncomplicate hematuria
d cystitis
(culture
not
required)
Recurrent
cystitis in
young
women
Symptoms
and a
urine
culture
with a
bacterial
count of
more than
•
•
•
Escherichia
coli
Staphylococc
us
saprophyticus
Proteus
mirabilis
Klebsiella
pneumoniae
•
•
•
•
•
•
Same as for
acute
uncomplicate
d cystitis
TMP-SMX
DS
(Bactrim,
Septra)
Trimethopri
m
(Proloprim)
Ciprofloxaci
n (Cipro)
Ofloxacin
(Floxin)
If the
patient has
more than
three
cystitis
episodes
per year,
treat
•
•
Threeday
course is
best
Quinolon
es may
be used
in areas
of TMPSMX
resistanc
e or in
patients
who
cannot
tolerate
TMP-SMX
Repeat
therapy
for seven
to 10
days
based on
culture
results
100 CFU
per mL of
urine
Urine
culture
with a
bacterial
Acute cystitis
count of
in young
1,000 to
men
10,000
CFU per
mL of
urine
prophylactic
ally with
postcoital,
patientdirected* or
continuous
daily
therapy
(see text)
•
Same as for
acute
uncomplicate
d cystitis
•
Same as for
acute
uncomplicat
ed cystitis
•
If gramnegative
organism,
oral
fluoroquinol
one
If grampositive
organism,
amoxicillin
If parenteral
administrati
on is
required,
ceftriaxone
(Rocephin)
or a
fluoroquinol
one
If
Enterococcu
s species,
add oral or
IV
amoxicillin
•
Urine
culture
Acute
with a
uncomplicate bacterial
d
count of
pyelonephriti 100,000
s
CFU per
mL of
urine
•
Same as for
acute
uncomplicate
d cystitis
•
•
Urine
Complicated culture
urinary tract with a
infection
bacterial
count of
•
•
•
•
E. coli
K.
pneumoniae
P. mirabilis
Enterococcus
•
If gramnegative
organism,
oral
fluoroquinol
and then
use
prophylac
tic
therapy
•
Treat for
seven to
10 days
•
Switch
from IV
to oral
administr
ation
when the
patient is
able to
take
medicatio
n by
mouth;
complete
a 14-day
course
•
Treat for
10 to 14
days
more than
10,000
CFU per
mL of
urine
Urine
culture
with a
bacterial
Asymptomati
count of
c bacteriuria
more than
in pregnancy
10,000
CFU per
mL of
urine
•
•
species
Pseudomonas
aeruginosa
Same as for
acute
uncomplicate
d cystitis
•
•
•
•
one
If
Enterococcu
s species,
ampicillin or
amoxicillin
with or
without
gentamicin
(Garamycin)
Amoxicillin
Nitrofuranto
in
(Macrodanti
n)
Cephalexin
(Keflex)
•
•
•
•
Symptoms
and a
urine
culture
Catheterwith a
associated
bacterial
urinary tract
count of
infection
more than
100 CFU
per mL of
urine
•
Depends on
duration of
catheterizatio
n
•
If gramnegative
organism, a
fluoroquinol
one
If grampositive
organism,
ampicillin or
amoxicillin
plus
gentamicin
•
TMP-SMX=trimethoprim-sulfamethoxazole; CFU=colonyforming unit; IV=intravenous.
*--Patient is given a prescription for an antibiotic to take if
symptoms develop.
Information from Stamm WE, Hooton TM. Management of
urinary tract infections in adults. N Engl J Med 1993;329:132834.
Avoid
tetracycli
nes and
fluoroqui
nolones
Treat for
three to
seven
days
Remove
catheter
if
possible,
and treat
for seven
to 10
days
For
patients
with
longterm
catheters
and
symptom
s, treat
for five to
seven
days
The diagnosis of UTI was once based on a quantitative urine culture yielding greater
than 100,000 colony-forming units (CFU) of bacteria per milliliter of urine, which was
termed "significant bacteriuria."7 This value was chosen because of its high
specificity for the diagnosis of true infection, even in asymptomatic persons.
However, several studies8-10 have established that one third or more of
symptomatic women have CFU counts below this level (low-coliform-count
infections) and that a bacterial count of 100 CFU per mL of urine has a high positive
predictive value for cystitis in symptomatic women. Unfortunately, some clinical
laboratories do not report counts of less than 10,000 CFU per mL of urine. As a
result, low-coliform-count infections are not diagnosed by these laboratories.
The microbiology of uncomplicated cystitis is limited to a few pathogens. As many as
90 percent of uncomplicated cystitis episodes are caused by Escherichia coli, 10 to
20 percent are caused by coagulase-negative Staphylococcus saprophyticus and 5
percent or less are caused by other Enterobacteriaceae organisms or enterococci.3 In
addition, the antimicrobial susceptibilities of these organisms are highly predictable.
Up to one third of uropathogens are resistant to ampicillin and sulfonamides, but the
majority are susceptible to trimethoprim-sulfamethoxazole (85 to 95 percent) and
fluoroquinolones (95 percent).3,11
TABLE 2
Diagnostic Tests for Urinary Tract Infections in Women
with Dysuria
Laboratory
test
Positive
Negative
Sensitivity Specificity predictive predictive
value
value
Midstream
culture
Any coliforms 1.00
0.71
0.79
1.00
More than
100 coliforms
0.95
per mL of
urine
0.85
0.88
0.94
More than
100,000
0.51
coliforms per
mL of urine
0.59
0.98
0.65
0.91
0.50
0.67
0.83
More than 20
white blood
0.50
cells per
mm3
0.95
0.94
0.54
0.95
0.50
0.92
Microscopy
More than 8
white blood
cells per
mm3
Rapid tests
Leukocyte
esterase
0.75 to
0.90
dipstick
Nitrite
dipstick
0.35 to
0.85
0.95
0.96
0.27 to
0.70
Leukocyte
0.75 to
esterase and
0.90
nitrite
0.70
0.75 to
0.93
0.41 to
0.95
Adapted with permission from Fihn SD, McGee SR. Outpatient
medicine. Philadelphia, Pa.: Saunders, 1992.
In view of the limited spectrum of causative organisms and their predictable
susceptibility, urine cultures and susceptibility testing add little to the choice of
antibiotic for the treatment of acute uncomplicated cystitis in young women.
Therefore, urine cultures are no longer advocated as part of the routine work-up of
these patients. Instead, these patients should undergo an abbreviated laboratory
work-up in which the presence of pyuria is confirmed by traditional urinalysis (wet
mount examination of spun urine), the cell-counting chamber technique or a dipstick
test for leukocyte esterase.3,6
An estimated 40 percent of women report having had a
UTI at some point in their lives.
A positive leukocyte esterase test has a reported sensitivity of 75 to 90 percent in
detecting pyuria associated with a UTI. Gram staining of unspun urine can be used to
detect bacteriuria. In this semiquantitative test, one organism per oil immersion field
correlates with 100,000 CFU per mL by culture.1 Because the procedure is timeconsuming and has low sensitivity, it is not routinely performed in most clinical
laboratories unless it is specifically requested. In today's office practice, the dipstick
test for nitrite is used as a surrogate marker for bacteriuria. It should be noted that
not all uropathogens reduce nitrates to nitrite. For example, enterococci, S.
saprophyticus and Acinetobacter species do not and therefore give false-negative
results. The sensitivities and specificities of the tests commonly used to diagnose
UTIs are given in Table 2.12
Treatment options for uncomplicated cystitis include single-dose antibiotic therapy
and three- or seven-day courses of antibiotics (Table 3). Treatment of cystitis with
seven or more days of antibiotics once was the standard of therapy. Although this
regimen was highly efficacious, it was associated with a certain (albeit low)
frequency of side effects. Single-dose therapy appears to offer the advantages of low
cost, high compliance and comparable efficacy. Studies using 3 g of amoxicillin, 400
mg of trimethoprim (Proloprim), two to three double-strength trimethoprimsulfamethoxazole tablets, 800 mg of norfloxacin (Noroxin), 125 mg of ciprofloxacin
(Cipro) or 200 mg of ofloxacin (Floxin) have confirmed that single-dose therapy is
highly effective in the treatment of acute uncomplicated cystitis, with cure rates
ranging from 80 to 99 percent.3
Fosfomycin tromethamine (Monurol) can be given as a single oral 3-g sachet for the
treatment of acute uncomplicated UTIs. This drug is active against E. coli,
enterococci and Citrobacter, Enterobacter, Klebsiella and Serratia species. The
clinical cure rate is estimated to be as high as 99 percent. Fosfomycin may be safely
used in pregnancy.13
Single-dose antibiotic therapy fell into disfavor when it was observed that women
had a high risk of recurrence within six weeks of the initial treatment.14,15 The risk
was attributed to the failure of single-dose antibiotics to eradicate gram-negative
bacteria from the rectum, the source or reservoir for ascending uropathogens.
TABLE 3
Antibiotic Therapy for Urinary Tract Infections
Diagnostic
group
Duration
Cost
Route of
of
Empiric options
(generic)*
administration
therapy
Acute
uncomplicated
urinary tract Oral
infections in
women
Three
days
Trimethoprimsulfamethoxazole
$ 7.50
(Bactrim DS), one
(2.00)
double-strength
tablet twice daily
Trimethoprim
(Proloprim), 100
mg twice daily
4.00 (1.00)
Norfloxacin
(Noroxin), 400
mg twice daily
18.50
Ciprofloxacin
(Cipro), 250 mg
twice daily
19.50
Lomefloxacin
(Maxaquin), 400
mg per day
20.00
Ofloxacin
(Floxin), 200 mg
twice daily
21.00
Enoxacin
(Penetrex), 200
mg twice daily
18.00
Sparfloxacin
(Zagam), 400 mg
25.00
as initial dose,
then 200 mg per
day
Levofloxacin
(Levaquin), 250
mg per day
19.00
Nitrofurantoin
(Macrodantin),
100 mg four
times daily
17.00
(14.00)
Cefpodoxime
(Vantin), 100 mg 17.00
twice daily
Cefixime
21.00
(Suprax), 400 mg
per day
Amoxicillinclavulanate
17.50
potassium
(Augmentin), 500
mg twice daily
Acute
uncomplicated Oral
pyelonephritis
14 days
Trimethoprimsulfamethoxazole
36.00
DS, one double(11.00)
strength tablet
twice daily
Ciprofloxacin, 500
105.50
mg twice daily
Levofloxacin, 250
92.00
mg per day
Enoxacin, 400 mg
191.00
twice daily
Sparfloxacin, 400
mg initial dose,
104.50
then 200 mg per
day
Ofloxacin, 400
mg twice daily
124.50
Cefpodoxime,
200 mg twice
daily
111.00
Cefixime, 400 mg
97.50
per day
Parenteral
Up to 3
days†
Trimethoprim32.00
sulfamethoxazole
(12.00) per
160/800 twice
day
daily
Ceftriaxone
(Rocephin), 1 g
per day
41.00 per
day
Ciprofloxacin, 400 57.50 per
mg twice daily
day
Ofloxacin, 400
mg twice daily
53.00 per
day
Levofloxacin, 250 21.00 per
mg
day
Complicated
urinary tract
infections
Oral
Parenteral
Aztreonam
(Azactam), 1 g
three times daily
48.50 per
day
Gentamicin
(Garamycin), 3
mg per kg per
day in 3 divided
doses every 8
hours‡§
12.50
(2.50 to
3.00) per
day
14 days
Fluoroquinolones
Up to 3
days
Ampicillin, 1 g
14.50
every six hours,
(5.00 to
and gentamicin, 3
5.50) per
mg per kg per
day
day‡
Urinary tract
infections in
young men
Oral
Seven
days
Trimethoprimsulfamethoxazole,
18.00
one double(5.50)
strength tablet
twice daily
Urinary tract
infections in
pregnant
women
Oral
Three to
seven
days
Amoxicillin, 250
mg three times
daily
2.00 to
4.50 (1.00
to 5.00)
Asymptomatic
bacteriuria in
Oral
pregnant
women
Three to
seven
days
Nitrofurantoin,
100 mg four
times daily
12.00 to
28.00
(14.00 to
32.50
*--Estimated cost to the pharmacist based on average
wholesale prices, rounded to the nearest half dollar, in Red
book. Montvale, N.J.: Medical Economics Data, 1998. Cost to
the patient will be higher, depending on prescription filling fee.
†--The Sanford guide (1998) recommends intravenous therapy
until patient is afebrile for 24 to 48 hours, then a two-week
course of oral therapy.
‡--Same regimens as for pyelonephritis.
§--Based on 70-kg (154-lb) patient.
Unlike single-dose antibiotic therapy, a three-day regimen reduces rectal carriage of
gram-negative bacteria and is not associated with a high recurrence rate. Thus,
three-day regimens appear to offer the optimal combination of convenience, low cost
and an efficacy comparable to that of seven-day or longer regimens but with fewer
side effects.11
One randomized trial16 compared three days of trimethoprim-sulfamethoxazole
therapy, one double-strength tablet twice daily, with three days of treatment using
the following drugs: nitrofurantoin (Macrodantin), 100 mg four times daily;
cefadroxil, 500 mg twice daily; and amoxicillin, 500 mg three times daily.
Trimethoprim-sulfamethoxazole was found to be the most cost-effective treatment.
Three-day regimens of ciprofloxacin, 250 mg twice daily, and ofloxacin, 200 mg
twice daily, were recently compared with three-day trimethoprim-sulfamethoxazole
therapy.3,11 The oral fluoroquinolones produced better cure rates with less toxicity,
but at a greater overall cost.
Quinolones that are useful in treating complicated and uncomplicated cystitis include
ciprofloxacin, norfloxacin, ofloxacin, enoxacin (Penetrex), lomefloxacin (Maxaquin),
sparfloxacin (Zagam) and levofloxacin (Levaquin).11 The newer fluoroquinolone,
sparfloxacin, in a dosage of 400 mg per day as the initial dose and then 200 mg per
day for two days, is equivalent to three days of therapy with ofloxacin or
ciprofloxacin. However, sparfloxacin can cause phototoxicity, and it has also been
associated with prolongation of the QT interval.17
As many as 90 percent of uncomplicated cystitis
episodes are caused by Escherichia coli, 10 to 20 percent
are caused by the coagulase-negative Staphylococcus
saprophyticus, and 5 percent or less are caused by other
Enterobacteriaceae organisms or enterococci.
On the basis of cost and efficacy, trimethoprim-sulfamethoxazole remains the
antibiotic of choice in the treatment of uncomplicated UTIs in young women. The use
of fluoroquinolones as first-line therapy for uncomplicated UTIs should be
discouraged, except in patients who cannot tolerate sulfonamides or trimethoprim,
who have a high frequency of antibiotic resistance because of recent antibiotic
treatment or who reside in an area in which significant resistance to trimethoprimsulfamethoxazole has been noted. Three days is the optimal duration of treatment
for uncomplicated cystitis. A seven-day course should be considered in pregnant
women, diabetic women and women who have had symptoms for more than than
one week and thus are at higher risk for pyelonephritis because of the delay in
treatment.
Recurrent Cystitis in Young Women
Up to 20 percent of young women with acute cystitis develop recurrent UTIs. During
these recurrent episodes, the causative organism should be identified by urine
culture and then documented to help differentiate between relapse (infection with
the same organism) and recurrence (infection with different organisms). Multiple
infections caused by the same organism are, by definition, complicated UTIs and
require longer courses of antibiotics and possibly further diagnostic tests (see the
discussion of complicated UTIs). Fortunately, most recurrent UTIs in young women
are uncomplicated infections caused by different organisms. These infections are
generally not associated with underlying anatomic abnormalities and do not require
further work-up of the genitourinary tract.5,11,18
Women who have more than three UTI recurrences documented by urine culture
within one year can be managed using one of three preventive strategies3,19:
1. Acute self-treatment with a three-day course of standard therapy.
2. Postcoital prophylaxis with one-half of a trimethoprim-sulfamethoxazole doublestrength tablet (40/200 mg) if the UTIs have been clearly related to intercourse.
3. Continuous daily prophylaxis with one of these regimens for a period of six
months: trimethoprim-sulfamethoxazole, one-half tablet per day (40/200 mg);
nitrofurantoin, 50 to 100 mg per day; norfloxacin, 200 mg per day; cephalexin
(Keflex), 250 mg per day; or trimethoprim, 100 mg per day.
Each of these regimens has been shown to decrease the morbidity of recurrent UTIs
without a concomitant increase in antibiotic resistance. Long-term studies have
shown antibiotic prophylaxis to be effective for up to five years with trimethoprim,
trimethoprim-sulfamethoxazole or nitrofurantoin, without the emergence of drug
resistance.3,19 Unfortunately, antibiotic prophylaxis does not appear to alter the
natural history of recurrences because 40 to 60 percent of these women reestablish
their pattern or frequency of infections within six months of stopping prophylaxis.19
Complicated UTI
A complicated UTI is one that occurs because of anatomic, functional or
pharmacologic factors that predispose the patient to persistent infection, recurrent
infection or treatment failure. These factors include conditions often encountered in
elderly men, such as enlargement of the prostate gland, blockages and other
problems necessitating the placement of indwelling urinary devices, and the
presence of bacteria that are resistant to multiple antibiotics. Although antibioticsusceptible E. coli is responsible for more than 80 percent of uncomplicated UTIs, it
accounts for fewer than one third of complicated cases.1,3 Clinically, the spectrum of
complicated UTIs may range from cystitis to urosepsis with septic shock.
Accurate urine culture and susceptibility information are necessary to best target and
eradicate the pathogens in complicated UTIs. These infections are usually associated
with high-count bacteriuria (greater than 100,000 CFU per mL of urine).
Occasionally, lower quantitative counts may be encountered in patients who are
undergoing diuresis or who are in renal failure. The initial empiric therapy for these
patients should include an agent with a broad spectrum of activity against the
expected uropathogens. Treatment most often includes a fluoroquinolone,
administered orally if possible. In patients who are unable to tolerate oral medication
or who require hospitalization for concomitant medical problems, appropriate initial
therapy may be parenteral administration of one of the following: a third-generation
cephalosporin with antipseudomonal activity such as ceftazidime (Fortaz) or
cefoperazone (Cefobid), cefepime (Maxipime), aztreonam (Azactam), imipenemcilastatin (Primaxin) or the combination of an antipseudomonal penicillin (ticarcillin
[Ticar], mezlocillin [Mezlin], piperacillin [Pipracil]) with an aminoglycoside.
Enterococci are frequently encountered uropathogens in complicated UTIs. In areas
in which vancomycin-resistant Enterococcus faecium is prevalent, the investigational
agent quinupristin-dalfopristin (Synercid) may be useful.20
Patients with complicated UTIs require at least a 10- to 14-day course of therapy.
Follow-up urine cultures should be performed within 10 to 14 days after treatment to
ensure that the uropathogen has been eradicated. Recent studies have shown that
patients initially placed on parenteral therapy can be switched to oral therapy within
72 hours as long as they are clinically improving and able to tolerate the oral agent,
and a regimen is available that covers the identified pathogen(s).11,21
Uncomplicated Pyelonephritis
Women with acute uncomplicated pyelonephritis may present with one of the
following: a mild cystitis-like illness and accompanying flank pain; a more severe
illness with fever, chills, nausea, vomiting, leukocytosis and abdominal pain; or a
serious gram-negative bacteremia. The microbiologic features of acute
uncomplicated pyelonephritis mirror cystitis, except that S. saprophyticus is a rare
cause. In most patients, uncomplicated pyelonephritis is caused by specific
uropathogenic strains of E. coli possessing adhesins that permit ascending infection
of the urinary tract.
The diagnosis should be confirmed by urinalysis with examination for pyuria and/or
white blood cell casts and by urine culture. Urine cultures demonstrate more than
100,000 CFU per mL of urine in 80 percent of women with pyelonephritis. Blood
cultures are positive in up to 20 percent of women who have this infection. With the
exceptions of white cell casts on urinalysis, and bacteremia and flank pain on
physical examination, none of the physical or laboratory findings are specific for
pyelonephritis.3
Oral therapy should be considered in women with mild to moderate symptoms who
are compliant with therapy and can tolerate oral antibiotics but do not have other
significant conditions, including pregnancy and gastrointestinal upset. Since E. coli
resistance to ampicillin, amoxicillin and first-generation cephalosporins exceeds 30
percent in most locales, these agents should not be used empirically for the
treatment of pyelonephritis.11 Even though trimethoprim-sulfamethoxazole is often
considered the treatment of choice, resistance to this drug combination may exceed
15 percent in some regions. In those instances, empiric therapy using an oral
fluoroquinolone should be considered.
Patients who are too ill to take oral antibiotics or who are unable to take them should
initially be treated with parenterally administered single agents, such as
trimethoprim-sulfamethoxazole, a third-generation cephalosporin, aztreonam, a
broad-spectrum penicillin, a quinolone or an aminoglycoside. The choice of antibiotic
is largely empiric, but Gram staining of the urine may be helpful. Once these patients
have improved clinically (usually by day 3), they can be switched to oral therapy
based on the results of culture and sensitivity studies.11
The total duration of therapy need not exceed 14 days, regardless of the initial
bacteremia. Patients with persistent symptoms after three days of appropriate
antimicrobial therapy should be evaluated by renal ultrasonography or computed
tomography for evidence of urinary obstruction or abscess. In the small percentage
of patients who relapse after a two-week course, a repeated six-week course is
usually curative.11
UTI in Men
Urinary tract infections most commonly occur in older men with prostatic disease,
outlet obstruction or urinary tract instrumentation. These infections occasionally
occur in young men who participate in anal sex (exposure to E. coli in the rectum),
who are not circumcised (increased E. coli colonization of the glans and prepuce) or
whose sexual partner is colonized with uropathogens.22
In men (unlike in women), a urine culture growing more than 1,000 CFU of a
pathogen per mL of urine is the best sign of a urinary tract infection, with a
sensitivity and specificity of 97 percent.23 Men with urinary tract infections should
receive a minimum of seven days of antibiotic therapy (either trimethoprimsulfamethoxazole or a fluoroquinolone). However, more extensive courses may be
required in, for example, men with associated urinary tract infection and prostatitis.
Consensus regarding the need for a urologic work-up in men with urinary tract
infections is lacking. Among young men with acute cystitis who respond to seven
days of treatment, diagnostic work-ups beyond cultures are generally
unrewarding.24 Urologic evaluation should be performed routinely in adolescents and
men with pyelonephritis or recurrent infections.11,25 When bacterial prostatitis is
the source of a urinary tract infection, eradication usually requires antibiotic therapy
for six to 12 weeks and in rare instances even longer.
Catheter-Associated UTI
Between 10 and 20 percent of patients who are hospitalized receive an indwelling
Foley catheter. Once this catheter is in place, the risk of bacteriuria is approximately
5 percent per day. With long-term catheterization, bacteriuria is inevitable. Catheter-
associated urinary tract infections account for 40 percent of all nosocomial infections
and are the most common source of gram-negative bacteremia in hospitalized
patients.26
Unlike single-dose antibiotic therapy, a three-day
regimen reduces rectal carriage of gram-negative
bacteria and is not associated with a high recurrence
rate. Thus, three-day regimens appear to offer the
optimal combination of convenience, low cost and an
efficacy comparable to that of seven-day or longer
regimens but with fewer side effects.
The diagnosis of catheter-associated urinary tract infection can be made when the
urine culture shows 100 or more CFU per mL of urine from a catheterized patient.
The microbiology of catheter-associated urinary tract infections includes E. coli and
Proteus, Enterococcus, Pseudomonas, Enterobacter, Serratia and Candida species.
The bacterial distribution reflects the nosocomial origin of the infections because so
many of the uropathogens are acquired exogenously via manipulation of the catheter
and drainage device. Bacteriuria is often polymicrobic, especially in patients with
long-term indwelling urinary catheters.
Symptomatic bacteriuria in a patient with an indwelling Foley catheter should be
treated with antibiotics that cover potential nosocomial uropathogens. Patients with
mild to moderate infections may be treated with one of the oral quinolones, usually
for 10 to 14 days. Parenteral antibiotic therapy may be necessary in patients with
severe infections or patients who are unable to tolerate oral medications. The
recommended duration of therapy for severe infections is 14 to 21 days. Treatment
is not recommended for catheterized patients who have asymptomatic bacteriuria,
with the following exceptions: patients who are immunosuppressed after organ
transplantation, patients at risk for bacterial endocarditis and patients who are about
to undergo urinary tract instrumentation.26
Bacteriuria is almost inevitable with long-term catheterization, and prevention
strategies have largely been unsuccessful. In such patients, catheters should be
changed periodically to prevent the formation of concretions and obstruction that can
lead to infection. Prophylactic systemic antibiotics have been shown to delay the
onset of bacteriuria in catheterized patients, but this strategy may lead to increased
bacterial resistance.26 Prophylactic antibiotic therapy has been successful in
reducing the frequency of bacteriuria only in patients who can be weaned from
indwelling catheters to intermittent catheterization.
Asymptomatic Bacteriuria
Asymptomatic bacteriuria is defined as the presence of more than 100,000 CFU per
mL of voided urine in persons with no symptoms of urinary tract infection. The
largest patient population at risk for asymptomatic bacteriuria is the elderly. Up to
40 percent of elderly men and women may have bacteriuria without symptoms.
Although early studies noted an association between bacteriuria and excess
mortality, more recent studies have failed to demonstrate any such link.27 In fact,
aggressively screening elderly persons for asymptomatic bacteriuria and subsequent
treatment of the infection has not been found to reduce either infectious
complications or mortality. Consequently, this approach currently is not
recommended.
Three groups of patients with asymptomatic bacteriuria have been shown to benefit
from treatment: (1) pregnant women, (2) patients with renal transplants and (3)
patients who are about to undergo genitourinary tract procedures.3 Between 2 and
10 percent of pregnancies are complicated by UTIs; if left untreated, 25 to 30
percent of these women develop pyelonephritis.28,29 Pregnancies that are
complicated by pyelonephritis have been associated with low-birth-weight infants
and prematurity. Thus, pregnant women should be screened for bacteriuria by urine
culture at 12 to 16 weeks of gestation. The presence of 100,000 CFU of bacteria per
mL of urine is considered significant.
Pregnant women with asymptomatic bacteriuria should be treated with a three- to
seven-day course of antibiotics, and the urine should subsequently be cultured to
ensure cure and the avoidance of relapse.29 Although amoxicillin is frequently
suggested as the agent of choice, E. coli is now commonly resistant to ampicillin,
amoxicillin and cephalexin. Thus, treatment should be based on the results of
susceptibility tests. Nitrofurantoin or trimethoprim-sulfamethoxazole may also be
used; however, caution should be exercised in the third trimester because the
sulfonamides compete with bilirubin binding in the newborn.
Symptomatic urinary tract infections complicate 1 to 2 percent of pregnancies,
usually in women with persistent bacteriuria.28,29 Most pregnant women with
pyelonephritis should be hospitalized. Initially, these patients should receive
intravenous antibiotic therapy. They should complete a 14-day course of acute
antibiotic therapy followed by nightly suppressive therapy until delivery. Recent
studies have shown that selected pregnant women with pyelonephritis can be treated
with either outpatient intramuscularly administered ceftriaxone (Rocephin) or orally
administered cephalexin.28 Ceftriaxone, a third-generation parenterally administered
cephalosporin, is a suitable agent for inpatient treatment. Tetracyclines and
fluoroquinolones should be avoided in pregnancy.
The Authors
ROBERT ORENSTEIN, D.O.,
is assistant professor in the Department of Internal Medicine at the Virginia
Commonwealth University Medical College of Virginia, Richmond. He is also director
of the HIV/AIDS Program at Hunter Holmes McGuire Veterans Affairs Medical Center,
also in Richmond. Dr. Orenstein graduated from the University of Osteopathic
Medicine and Health Sciences, Des Moines, Iowa. He completed a residency in
internal medicine at Geisinger Medical Center, Danville, Pa., and a fellowship in
infectious diseases at the Medical College of Virginia.
EDWARD S. WONG, M.D.,
is associate professor in the Department of Internal Medicine at Virginia
Commonwealth University Medical College of Virginia and chief of the infectious
diseases section at Hunter Holmes McGuire Veterans Affairs Medical Center. Dr.
Wong received his medical degree from Harvard Medical School, Boston. He
completed a residency in internal medicine at Montefiore Hospital, New York, N.Y.,
and a fellowship in infectious diseases at the University of Washington Medical
Center, Seattle.