Cystitis in Female

Background
Urinary tract infections (UTIs) are common in females, and cystitis (bladder infection)
represents the majority of these infections. Related terms include pyelonephritis, which refers
to upper urinary tract infection; bacteriuria, which describes bacteria in the urine; and
candiduria, which describes yeast in the urine. Very ill patients may be referred to as having
urosepsis.

UTI is defined as significant bacteriuria in the setting of symptoms of cystitis or

pyelonephritis. These infections account for a significant number of emergency department
(ED) visits,[1] and 20% of women develop at least one UTI. (See Epidemiology.)

Escherichia coli causes the majority of uncomplicated cystitis cases. Among the pathogens
responsible for the remainder are Staphylococcus saprophyticus, Proteus mirabilis, Klebsiella
pneumonia e, or Enterococcus faecalis. (See Etiology.)

A presumptive diagnosis of uncomplicated cystitis can be made on the basis of findings on

the history and physical examination, along with urinalysis.[2, 3] Proper specimen collection is
necessary. In addition, clinicians need to appreciate the epidemiological and host factors that
may identify patients with complicated cystitis or clinically inapparent upper UTI, in whom
more comprehensive assessment is indicated. (See Workup.)

Successful emergent management includes selection of appropriate antimicrobial therapy

with recommendations for follow-up care. Oral therapy with an antibiotic effective against
gram-negative aerobic coliform bacteria is the principal therapeutic intervention in patients
with cystitis. (See Treatment, as well as Medication.)

The following terms are defined for uniformity in this article:

 Asymptomatic bacteriuria (ASB) refers to 2 consecutive urine cultures growing more

than 100,000 colony-forming units (CFU)/mL of a bacterial species in a patient
lacking symptoms of a UTI
 Uropathogens are bacteria with specific virulence factors that facilitate their invasion
of the urinary tract
 Complicated UTIs are defined as UTIs that are associated with metabolic disorders,
that are secondary to anatomic or functional abnormalities that impair urinary tract
drainage, or that involve unusual pathogens (eg, yeast), which increases the risk of
therapeutic failure

Pathophysiology
The urinary tract is normally sterile. Uncomplicated UTI involves the urinary bladder in a
host without underlying renal, metabolic, or neurologic diseases. Cystitis represents bladder
mucosal invasion, most often by enteric coliform bacteria (eg, Escherichia coli) that inhabit
the periurethral vaginal introitus and ascend into the bladder via the urethra.
In recurrent E coli UTIs, peak colonization rates of the periurethral area 2-3 days prior to the
development of the symptoms of acute cystitis range from 46-90%. During this same period,
asymptomatic bacteriuria rates increase from 7% to 70%.[4]

Because sexual intercourse may promote this migration, cystitis is common in otherwise
healthy young women. Generally, urine is a good culture medium. Factors unfavorable to
bacterial growth include a low pH (5.5 or less), a high concentration of urea, and the presence
of organic acids derived from a diet that includes fruits and protein. Organic acids enhance
acidification of the urine.

Frequent and complete voiding has been associated with a reduction in the incidence of UTI.
Normally, a thin film of urine remains in the bladder after emptying, and any bacteria present
are removed by the mucosal cell production of organic acids.

If the defense mechanisms of the lower urinary tract fail, upper tract or kidney involvement
occurs and is termed pyelonephritis. Host defenses at this level include local leukocyte
phagocytosis and renal production of antibodies that kill bacteria in the presence of
complement. For more information on this topic, see the Medscape Reference articles Acute
Pyelonephritis and Pathophysiology of Complicated Urinary Tract Infections.

In general, there are 3 main mechanisms responsible for UTIs:

 Colonization with ascending spread

 Hematogenous spread
 Periurogenital spread

Bacterial virulence

Uropathogenic bacteria, derived from a subset of fecal flora, have traits that enable
adherence, growth, and resistance of host defenses. These traits facilitate colonization and
infection of the urinary tract.

Adhesins are bacterial surface structures that enable attachment to host membranes. In E coli
infection, these include both pili (ie, fimbriae) and outer-membrane proteins (eg, Dr
hemagglutinin). P fimbriae , which attach to globoseries-type glycolipids found in the colon
and urinary epithelium, are associated with pyelonephritis and cystitis and are found in many
E coli strains that cause urosepsis.

Type 1 fimbriae bind to mannose-containing structures found in many different cell types,
including Tamm-Horsfall protein (the major protein found in human urine). Whether this
facilitates or inhibits uroepithelial colonization is the subject of some debate.

Other factors that may be important for E coli virulence in the urinary tract include capsular
polysaccharides, hemolysins, cytotoxic necrotizing factor (CNF) protein, and aerobactins.
Several Kauffman serogroups of E coli that contain these virulence factors may be more
likely to cause UTIs, including O1, O2, O4, O6, O16, and O18.

Another example of bacterial virulence is the swarming capability of Proteus mirabilis.

Swarming involves the expression of specific genes when these bacteria are exposed to
surfaces such as catheters. This results in the coordinated movement of large numbers of
bacteria, enabling P mirabilis to move across solid surfaces. This likely explains the
association of P mirabilis UTIs with instrumentation of the urinary tract.

Host resistance

Most uropathogens gain access to the urinary tract via an ascending route. The shorter length
of the female urethra allows uropathogens easier access to the bladder. The continuous
unidirectional flow of urine helps to minimize UTIs, and anything that interferes with this
increases the host's susceptibility to UTI. Examples of interference include volume depletion,
sexual intercourse, urinary tract obstruction, instrumentation, use of catheters not drained to
gravity, and vesicoureteral reflux.

Secretory defenses help promote bacterial clearance and prevent adherence. Secretory
immunoglobulin A (IgA) reduces attachment and invasion of bacteria in the urinary tract.
Women who are nonsecretors of the ABH blood antigens appear to be at higher risk for
recurrent UTIs; this may occur because of a lack of specific glycosyltransferases that modify
epithelial surface glycolipids, allowing E coli to bind to them better.

In premenopausal women, lactobacilli are the predominant vaginal flora and serve to
suppress vaginal colonization by the uropathogens. Most antibiotics, except sulfamethoxazole
and the quinolones, can eradicate these protective bacteria.

Urine itself has several antibacterial features that suppress UTIs. Specifically, the pH, urea
concentration, osmolarity, and various organic acids prevent most bacteria from surviving in
the urinary tract.

Etiology
E coli causes 70-95% of both upper and lower UTIs. Various organisms are responsible for
the remainder of infections, including S saprophyticus, Proteus species, Klebsiella species,
Enterococcus faecalis, other Enterobacteriaceae, and yeast. Some species are more common
in certain subgroups, such as Staphylococcus saprophyticus in young women.

Most complicated UTIs are nosocomial in origin. Increasingly, UTIs in patients in health care
institutions and in those with frequent antibiotic exposure are caused by multidrug-resistant
gram-negative pathogens, such as extended-spectrum beta-lactamase (ESBL) and
carbapenemase producers. However, the prevalence of multidrug-resistant pathogens varies
by locale.[5]

The most important risk factor for bacteriuria is the presence of a catheter.[6] Eighty percent
of nosocomial UTIs are related to urethral catheterization, while 5-10% are related to
genitourinary manipulation. Catheters inoculate organisms into the bladder and promote
colonization by providing a surface for bacterial adhesion and causing mucosal irritation. For
more information on this topic, see the Medscape Reference article Catheter-Related Urinary
Tract Infection.

Sexual intercourse contributes to increased risk, as does use of a diaphragm and/or

spermicide. Routine pelvic examinations are also associated with an increased risk of a UTI
for 7 weeks post procedure.[7] Women who are elderly, are pregnant, or have preexisting
urinary tract structural abnormalities or obstruction carry a higher risk of UTI.

UTIs are the most common type of infection following renal transplantation. Susceptibility is
especially high in the first 2 months following transplantation. Triggering factors include
vesicoureteral reflux and immunosuppression. Corynebacterium urealyticum (ie, CDC group
D2) has been reported to cause encrusted pyelitis and cystitis in these patients.

Calculi related to UTIs most commonly occur in women who experience recurrent UTIs with
Proteus, Pseudomonas, and Providencia species. Perinephric abscesses are associated most
commonly with E coli, Proteus species, and S aureus but also may be secondary to
Enterobacter, Citrobacter, Serratia, Pseudomonas, and Klebsiella species. More unusual
causes include enterococci, Candida species, anaerobes, Actinomyces species, and
Mycobacterium tuberculosis. Twenty-five percent of infections are polymicrobial.

Candiduria is defined as more than 1000 CFU/mL of yeast from 2 cultures. Candida
albicans, which is germ tube positive, is the usual culprit. Germ tube–negative Candida
species (tropicalis, parapsilosis, glabrata, lusitaniae, krusei) are less common.

Risk factors for candiduria include diabetes mellitus, indwelling urinary catheters, and
antibiotic use. Candiduria may clear spontaneously or may result in (or from) deep fungal
infections.

Epidemiology
United States statistics

UTIs in women are very common; approximately 25-40% of women in the United States
aged 20-40 years have had a UTI. UTIs account for over 6 million patient visits to physicians
per year in the United States. Approximately 20% of those visits are to EDs.

Cystitis occurs in 0.3-1.3% of pregnancies but does not appear to be related to asymptomatic
bacteriuria. Acute pyelonephritis occurs in 1-2% of pregnancies. UTIs occur in 30-50% of
renal transplant patients and frequently are silent.

In 2007, approximately 3.9% of office visits were related to symptoms involving the
genitourinary tract.[8] Estimates based on office and ED visits suggest per annum about 7
million episodes of acute cystitis. Some studies estimate that UTIs (cystitis plus
pyelonephritis) cost at least $1 billion per year.

International statistics

UTIs have been well studied in Sweden and other parts of Europe.[9] These studies have
shown that 1 in 5 adult women experience a UTI at some point, confirming that it is an
exceedingly common worldwide problem.

The epidemiology of UTI in the tropics is less well documented. UTIs appear to be common
and associated with structural abnormalities. Chronic infection from Schistosoma
haematobium disrupts bladder mucosal integrity and causes urinary tract obstruction and
stasis. Salmonella bacteriuria, with or without bacteremia, is very common in patients with
schistosomiasis. Treatment requires both antischistosomal and anti-Salmonella agents.

Age- and sex-related demographics

Uncomplicated UTIs are much more common in women than men when matched for age. A
study of Norwegian men aged 21-50 years showed an approximate incidence of 0.0006-
0.0008 infections per person-year, compared with approximately 0.5-0.7 per person-year in
similarly aged women in the United States.

The largest group of patients with UTI is adult women. The incidence of UTI in women tends
to increase with increasing age. Several peaks above baseline correspond with specific
events, including an increase in women aged 18-30 years (associated with coitus—so-called
honeymoon cystitis—and pregnancy).

Rates of infection are high in postmenopausal women because of bladder or uterine prolapse
causing incomplete bladder emptying; loss of estrogen with attendant changes in vaginal flora
(notably, loss of lactobacilli), which allows periurethral colonization with gram-negative
aerobes, such as E coli; and higher likelihood of concomitant medical illness, such as
diabetes.

Of neonates, boys are slightly more likely than girls to present with UTI as part of a gram-
negative sepsis syndrome. The incidence in preschool-aged children is approximately 2% and
is 10 times more common in girls. UTI occurs in 5% of school-aged girls, but it is rare in
school-aged boys.

Prognosis
Even with effective antibiotic treatment, the average duration of severe symptoms in women
with cystitis is somewhat longer than 3 days. Features that have been associated with a more
prolonged course than average include a history of somatization, previous cystitis, urinary
frequency, and more severe symptoms at baseline.[10] .

Although simple lower UTI (cystitis) may resolve spontaneously, effective treatment lessens
the duration of symptoms and reduces the incidence of progression to upper UTI. Even with
effective treatment, however, about 25% of women with cystitis will experience a recurrence.

Younger patients have the lowest rates of morbidity and mortality. Factors associated with an
unfavorable prognosis include the following:

 Old age
 General debility
 Renal calculi or obstruction
 Recent hospitalization
 Urinary tract instrumentation or antibiotic therapy
 Diabetes mellitus
 Chronic nephropathy
 Sickle cell anemia
 Underlying cancer
  Intercurrent chemotherapy

The mortality associated with acute uncomplicated cystitis in women aged 20-60 years
appears to be negligible. A longitudinal cohort study of Swedish women showed a higher
mortality in women with a history of UTI than in age-matched women without such a history
(37% versus 28% in 10 y),[11] but these cohorts were not matched for other mortality-related
factors, making it difficult to attribute the increased mortality to UTIs.

In contrast, the morbidity in terms of quality of life and economic measures is tremendous.
Each episode of UTI in a young woman results in an average of 6.1 days of symptoms, 1.2
days of decreased class/work attendance, and 0.4 days in bed.

Nosocomial infections develop in about 5% of patients admitted to hospitals, and UTIs

account for 40% of these infections. From 2-4% of these patients become bacteremic, with a
mortality of 12.5%.

Patient Education
Proper adherence to the outpatient medical regimen should be stressed. Behavior
modification, such as good oral fluid intake to enhance diuresis and frequent voiding
(including postintercourse voiding) may be helpful in reducing recurrent infection. (See
Prevention of Urinary Tract Infections.)

For patient education information, see the Kidneys and Urinary System Center, as well as
Urinary Tract Infections, Blood in the Urine, Birth Control Overview, Birth Control
Spermicides, and Birth Control FAQs.

History
The classic symptoms of urinary tract infection (UTI) in the adult are primarily dysuria with
accompanying urinary urgency and frequency. A sensation of bladder fullness or lower
abdominal discomfort is often present.

Because of the referred pain pathways, even simple lower UTI may be accompanied by flank
pain and costovertebral angle tenderness. In the emergency department, however, assume that
the presence of these symptoms represents upper UTI.

Bloody urine is reported in as many as 10% of cases of UTI in otherwise healthy women; this
condition is called hemorrhagic cystitis. Fevers, chills, and malaise may be noted in patients
with cystitis, though these findings are associated more frequently with upper UTI (ie,
pyelonephritis).

A history of vaginal discharge suggests that vaginitis, cervicitis, or pelvic inflammatory

disease is responsible for symptoms of dysuria; therefore, a pelvic examination must be
performed. Important additional information includes a history of prior sexually transmitted
disease (STD) and multiple current sexual partners.

Physical Examination
The patient appears uncomfortable but not toxic. The presence of toxic fever, chills, nausea,
and vomiting suggests pyelonephritis rather than cystitis; however, immunosuppressed and
even immunocompetent patients with pyelonephritis may exhibit few, if any, of these
symptoms. In elderly women, 50% of cases of cystitis also involve the upper tracts.[11]

The clinician may appreciate signs of dehydration, such as dry mucous membranes and
tachycardia. Clammy extremities and symptomatic orthostasis suggest poor vascular tone due
to gram-negative bacteremia rather than simple cystitis.

Most adult women with simple lower UTI have suprapubic tenderness. Pelvic examination
should be performed to exclude vaginitis, cervicitis, or pelvic tenderness (eg, cervical motion
tenderness, which suggests pelvic inflammatory disease).

Acute Urethritis Versus Cystitis

The symptoms of acute urethritis overlap with those of cystitis, including acute dysuria and
urinary hesitancy. Fever may be a component of urethritis-related syndromes (eg, Reiter
syndrome, Behçet syndrome) but rarely is observed in acute cystitis. Urethral discharge is
much more suggestive of urethritis, while bladder-related symptoms, such as urgency,
polyuria, and incomplete voids, are more consistent with cystitis.

The predominant complaints in acute cystitis relate to the inflamed bladder mucosa.
Constitutional symptoms, such as fever, nausea, and anorexia, are rare or mild. The
symptoms of dysuria, urgency, hesitancy, polyuria, and incomplete voids may be
accompanied by urinary incontinence, gross hematuria, and suprapubic or low back pain.
Patients may demonstrate some suprapubic tenderness to palpation.

Abnormal physical examination findings are generally lacking in women with acute cystitis.
The pelvic examination reveals no abnormalities unless another process, such as vaginitis, is
mimicking or occurring simultaneously with cystitis.

Infection in Patients with Spinal Cord Injury

In patients with spinal cord injury, the following signs and symptoms are suggestive of a
UTI:

 Malodorous and cloudy urine

 Muscular spasticity
 Fatigue
 Fevers
 Chills
 Autonomic instability

Patients with lesions above T6 may exhibit autonomic dysreflexia to noxious stimuli, such as
an overdistended bladder. The sympathetic response below the level of injury is uninhibited,
producing severe vasoconstriction and reflexive bradycardia. If the patient is febrile, this may
appear as a pulse-temperature dissociation.
For more information on this topic, see the Medscape Reference article Urinary Tract
Infections in Spinal Cord Injury.

Catheter-Related Infection
Symptoms of catheter-related UTI generally are nonspecific; most patients present with fever
and leukocytosis. Significant pyuria generally is represented by more than 50 white blood
cells per high-power field (WBC/hpf). Colony counts on a urine culture range from 100-
10,000 CFU/mL. Infections may be polymicrobial. Pyuria and elevated bacterial colony
counts are seen in all patients in whom a catheter has been in place for more than a few days.
In this situation, their presence is not synonymous with a UTI.[6]

For more information on this topic, see the Medscape Reference article Catheter-Related
Urinary Tract Infection.

Infection in Pregnant Patients

Asymptomatic bacteriuria (ASB) occurs in 5-10% of pregnant women. More than 100,000
CFU/mL of a single uropathogen is the classic definition of ASB, but more recent data
support 10,000 CFU/mL from a clean-catch specimen as a threshold.

ASB most commonly appears between the ninth and 17th weeks of pregnancy. ASB
predisposes to preterm labor, intrauterine growth retardation, low-birth-weight infants,
anemia, amnionitis, and hypertensive disorders of pregnancy.

Risk factors include sexual activity, increasing age and parity, diabetes, lower socioeconomic
class, a history of UTIs, sickle cell disease, and structural/functional abnormalities. Cystitis
occurs in 0.3-1.3% of pregnancies but does not appear to be related to ASB.

The recommendation is to screen pregnant women at their first prenatal visit and during the
third trimester. Further screening is not indicated unless the initial test result is positive or the
patient develops symptoms.

For more information, see the Medscape Reference topic Urinary Tract Infections in
Pregnancy.

Infection in Patients with Diabetes Mellitus

Complicated UTIs in patients who have diabetes include renal and perirenal abscess,
emphysematous pyelonephritis, emphysematous cystitis, fungal infections,
xanthogranulomatous pyelonephritis, and papillary necrosis. Susceptibility increases with
longer duration and greater severity of diabetes.

For more information on this topic, see the Medscape Reference article Urinary Tract
Infections in Diabetes Mellitus.

Diagnostic Considerations
Occult pyelonephritis occurs in 15-50% (or more) of all urinary tract infections (UTIs), based
on several studies on localization of organisms within the urinary tract. This usually occurs in
older women. It appears that these patients are unable to mount a fever or develop an elevated
white count or costovertebral angle (CVA) tenderness. These patients may present with an
unexplained fall or a change in mental status.

Postmenopausal women may also experience senile urethritis. In addition to urinary burning,
frequency, and urgency, these patients may complain of vaginal and vulvar itching and
discharge. Physical examination reveals a dry, pale vaginal epithelium and eversion of the
urethral mucosa. Senile urethritis responds to topical estrogen therapy.

The differential diagnosis for infectious causes of sterile pyuria includes perinephric abscess,
urethral syndrome, renal tuberculosis, and fungal infections of the urinary tract system.
Noninfectious causes of pyuria include the following:

 Uric acid and hypercalcemic nephropathy

 Lithium and heavy metal toxicity
 Sarcoidosis and other granulomatous diseases (eg, tuberculosis)
 Interstitial cystitis
 Polycystic kidney disease
 Genitourinary malignancy
 Renal transplant rejection
 Any periurethral process

Consider UTI in any condition involving pain the flank and back or pain in the abdomen and
pelvis. Also consider cervicitis and Chlamydia infection. Do not assume that a sexually active
female with dysuria has a UTI without first excluding the possibility of sexually transmitted
disease–related cervicitis, vaginitis, or pelvic inflammatory disease.

UTIs in pregnancy have potentially adverse outcomes for both the mother and the fetus.
Obtain a urine culture in all pregnant patients with suspected UTI, as the results may provide
the physician or the follow-up physician with valuable information if the patient does not
respond as expected to treatment. Pyuria and bacteriuria are always treated during pregnancy,
regardless of whether symptoms are present.

Patients with diabetes mellitus are at increased risk for complicated UTIs. Diagnostic
considerations include the following:

 Renal and perirenal abscess

 Emphysematous pyelonephritis
 Emphysematous cystitis
 Fungal infections
 Xanthogranulomatous pyelonephritis
 Papillary necrosis

Older patients who appear toxic are more likely to have obstruction complicating their UTI.
Obtain a structural study to rule out this possibility.

Differentials
  Bladder Cancer
 Chlamydial Genitourinary Infections
 Cystitis, Nonbacterial
 Herpes Simplex
 Interstitial Cystitis
 Pelvic Inflammatory Disease
 Pyelonephritis, Acute
 Urethritis
 Vaginitis

Approach Considerations
In the 1980s, many experts felt that urine cultures were unnecessary in young women with
probable cystitis because almost all of these were caused by pan-susceptible isolates of
Escherichia coli. Since then, however, antibiotic resistance in uropathogenic E coli has
become a significant concern. Resistance has also been emerging among other common
cystitis pathogens, including Enterococcus faecalis, Staphylococcus saprophyticus, Klebsiella
pneumoniae, and Proteus mirabilis.

Trimethoprim-sulfamethoxazole (TMP-SMX) resistance has reached levels as high as 20% in

some communities. Substitution of fluoroquinolones has resulted in an increase in resistance
to these drugs, as well.[12]

Nevertheless, according to guidelines from the American College of Obstetricians and

Gynecologists, a urine culture is not required for the initial treatment of women with a
symptomatic lower urinary tract infection (UTI) with pyuria or bacteriuria or both.[13] In a
United Kingdom study, dipstick diagnosis proved more cost-effective than positive
midstream urine culture for targeting antibiotic therapy.[2]

Consider obtaining urine cultures in cases of cystitis in immunosuppressed patients and those
with a recent history of instrumentation, exposure to antibiotics, or recurrent infection.
Obtaining cultures is also advisable in elderly women, who have a high rate of upper tract
involvement.

Microscopic hematuria is found in about half of cystitis cases; when found without symptoms
or pyuria, it should prompt a search for malignancy. Other possibilities to be considered in
the differential diagnosis include calculi, vasculitis, renal tuberculosis, and
glomerulonephritis.

In a developing country, hematuria is suggestive of schistosomiasis. Retention of

Schistosoma haematobium eggs and formation of granulomas in the urinary tract can lead not
only to hematuria but also to dysuria, bladder polyps and ulcers, and even obstructive
uropathies. Schistosomiasis can also be associated with salmonellosis and squamous cell
malignancies of the bladder.

Bacteremia is associated with pyelonephritis, corticomedullary abscesses, and perinephric

abscesses. Approximately 10-40% of patients with pyelonephritis or perinephric abscesses
have positive results on blood culture. Bacteremia is not necessarily associated with a higher
morbidity or mortality in women with uncomplicated UTI.
Cervical swabs may be indicated in cases of possible pelvic inflammatory disease.

Visual inspection of the urine is not helpful. Cloudiness of the urine is most often due to
protein or crystal presence, and malodorous urine may be due to diet or medication use.

No imaging studies are indicated in the routine evaluation of cystitis. Renal function testing is
not indicated in most episodes of UTI, but it may be helpful in patients with known urinary
tract structural abnormality or renal insufficiency. Renal function testing also may be helpful
in older, particularly ill-appearing hosts or in hosts with other complications.

Urinalysis
The most accurate method to measure pyuria is counting leukocytes in unspun fresh urine
using a hemocytometer chamber; greater than 10 white blood cells (WBCs)/mL is considered
abnormal. Counts determined from a wet mount of centrifuged urine are not reliable
measures of pyuria. A noncontaminated specimen is suggested by a lack of squamous
epithelial cells. Pyuria is a sensitive (80-95%) but nonspecific (50-76%) sign of UTI.

White cell casts may be observed in conditions other than infection, and they may not be
observed in all cases of pyelonephritis. If the patient has evidence of acute infection and
white cell casts are present, however, the infection likely represents pyelonephritis. A spun
sample (5 mL at 2000 revolutions per min [rpm] for 5 min) is best used for evaluation of
cellular casts.

Proteinuria is commonly observed in infections of the urinary tract, but the proteinuria
usually is low grade. More than 2 g of protein per 24 hours suggests glomerular disease.

Approximately 70% of patients with corticomedullary abscesses have abnormal urinalysis

findings, whereas those with renal cortical abscesses usually have normal findings. Two
thirds of patients with perinephric abscesses have an abnormal urinalysis.

Urine specimen collection

Urine specimens may be obtained by midstream clean catch, suprapubic aspiration, or

catheterization.

The midstream-voided technique is as accurate as catheterization if proper technique is

followed. Instruct the woman to remove her underwear and sit facing the back of the toilet.
This promotes proper positioning of the thighs.

Instruct the patient to spread the labia with one hand and cleanse from front to back with
povidone-iodine or soaped swabs with the other hand; then pass a small amount of urine into
the toilet; and finally urinate into the specimen cup. The use of a tampon may allow a proper
specimen if heavy vaginal bleeding or discharge is present.

Midstream urine specimens may become contaminated, particularly if the woman has
difficulty spreading and maintaining separation of the labia. The presence of squamous cells
and lactobacilli on urinalysis suggests contamination or colonization (see image below).
Catheterization may be needed in some women to obtain a clean specimen, although it poses
the risk of iatrogenic infection.[14]

Lactobacilli and a squamous epithelial cell are evident on this

vaginal smear. The presence of squamous cells and lactobacilli on urinalysis suggests
contamination or colonization. Source: Centers for Disease Control and Prevention, Dr. Mike
Miller

Although the use of midstream urine specimens is widely advocated, one randomized trial in
young women showed that the rate of contamination was nearly identical among those who
used midstream clean-catch technique and those who urinated into a container without
cleansing the perineum or discarding the first urine output. Use of a vaginal tampon in
addition to clean-catch technique had no significant effect on the contamination rate.[15]

Dipstick testing

Dipstick testing should include glucose, protein, blood, nitrite, and leukocyte esterase.
Leukocyte esterase is a dipstick test that can rapidly screen for pyuria; it is 57-96% sensitive
and 94-98% specific for identifying pyuria. Given this broad range of sensitivity, it is
important to consider the possibility of false-positive results, particularly with asymptomatic
patients undergoing evaluation for recurrent UTI.

Pyuria, as indicated by a positive result of the leukocyte esterase dipstick test, is found in the
vast majority of patients with UTI. This is an exceedingly useful screening examination that
can be performed promptly in any ED setting. If pyuria is absent, the diagnosis of UTI should
be questioned until urine culture results become available.

In a United Kingdom study, dipstick diagnosis based on findings of nitrite or both leukocyte
esterase and blood was 77% sensitive and 79% specific, with a positive predictive value of
81% and a negative predictive value of 65%.[2] Diagnosis on clinical grounds proved less
sensitive.

Urine microscopy

A microscopic evaluation of the urine sample for WBC counts, RBC counts, and cellular or
hyaline casts should be performed. In the office, a combination of clinical symptoms with
dipstick and microscopic analysis showing pyuria and/or positive nitrite and leukocyte
esterase tests can be used as presumptive evidence of UTI.

Low-level pyuria (6-20 WBCs per high-power field [hpf] microscopy on a centrifuged
specimen) may be associated with an unacceptable level of false-negative results with the
leukocyte esterase dipstick test, as Propp et al found in an ED setting.[16]
In females with appropriate symptoms and examination findings suggestive of UTI, urine
microscopy may be indicated despite a negative result of the leukocyte esterase dipstick test.
Current emphasis in the diagnosis of UTI rests with the detection of pyuria. As noted, a
positive leukocyte esterase dipstick test suffices in most instances.

According to Stamm et al, levels of pyuria as low as 2-5 WBCs/hpf in a centrifuged specimen
are important in females with appropriate symptoms. The presence of bacteriuria is
significant. However, the presence of numerous squamous epithelial cells raises the
possibility of contamination.[14] Low-level or, occasionally, frank hematuria may be noted in
otherwise typical UTI; however, its positive predictive value is poor.

Nitrate test

Nitrate tests detect the products of nitrate reductase, an enzyme produced by many bacterial
species. These products are not present normally unless a UTI exists. This test has a
sensitivity and specificity of 22% and 94-100%, respectively. The low sensitivity has been
attributed to enzyme-deficient bacteria causing infection or low-grade bacteriuria.

A positive result on the nitrate test is highly specific for UTI, typically because of urease-
splitting organisms, such as Proteus species and, occasionally, E coli; however, it is very
insensitive as a screening tool, as only 25% of patients with UTI have a positive nitrate test
result.

Urine Culture
Urine culture remains the criterion standard for the diagnosis of UTI. Collected urine should
be sent for culture immediately; if not, it should be refrigerated at 4°C. Two culture
techniques (dip slide, agar) are widely used and accurate.

The 2010 Infectious Disease Society of America (IDSA) consensus limits for cystitis and
pyelonephritis in women are more than 1000 colony-forming units (CFU)/mL and more than
10,000 CFU/mL, respectively, for clean-catch midstream urine specimens. Historically, the
definition of UTI was based on the finding at culture of 100,000 CFU/mL of a single
organism. However, this misses up to 50% of symptomatic infections, so the lower colony
rate of greater than 1000 CFU/mL is now accepted.[17]

The definition of asymptomatic bacteriuria still uses the historical threshold. Asymptomatic
bacteruria in a female is defined as a urine culture (clean-catch or catheterized specimen)
growing greater than 100,000 CFU/mL in an asymptomatic individual.

Note that any amount of uropathogen grown in culture from a suprapubic aspirate should be
considered evidence of a UTI. Approximately 40% of patients with perinephric abscesses
have sterile urine cultures.

An uncomplicated UTI (cystitis) does not require a urine culture unless the woman has
experienced a failure of empiric therapy. Obtain a urine culture in patients suspected of
having an upper UTI or a complicated UTI, as well in those in whom initial treatment fails.
If the patient has had a UTI within the last month, relapse is probably caused by the same
organism. Relapse represents treatment failure. Reinfection occurs in 1-6 months and usually
is due to a different organism (or serotype of the same organism). Obtain a urine culture for
patients who are reinfected.

If a Gram stain of an uncentrifuged, clean-catch, midstream urine specimen reveals the

presence of 1 bacterium per oil-immersion field, it represents 10,000 bacteria/mL of urine. A
specimen (5 mL) that has been centrifuged for 5 minutes at 2000 rpm and examined under
high power after Gram staining will identify lower numbers. In general, a Gram stain has a
sensitivity of 90% and a specificity of 88%.

Complete Blood Cell Count

A CBC is not helpful in differentiating upper from lower UTI or in making decisions
regarding admission. However, significant leukopenia in hosts who are older or
immunocompromised may be an ominous finding.

The WBC count may or may not be elevated in patients with uncomplicated UTI, but it is
usually elevated in patients with complicated UTIs. Patients with complicated UTIs may have
anemia; for example, anemia is observed in 40% of patients with perinephric abscesses.

Diagnostic Catheterization
Catheterization is indicated if the patient cannot void spontaneously, if the patient is too
debilitated or immobilized, or if obesity prevents the patient from obtaining a suitable
specimen. Measurement of postvoiding residual urine volume by catheterization may reveal
urinary retention in a host with a defective bladder-emptying mechanism.

Measurement of the postvoid residual volume should be strongly considered in all patients
who require hospital-level care. Handheld portable bladder scans may also be used as a
noninvasive alternative.

Guidelines from the Centers for Disease Control and Prevention (CDC) advise that in acute
care hospital settings, aseptic technique and sterile equipment for catheter insertion must be
used to minimize the risk of catheter-associated UTI. Only properly trained individuals who
are skilled in the correct technique of aseptic catheter insertion and maintenance should take
on this task.[18]

For more information on this procedure, see the Medscape Reference article Urethral
Catheterization in Women.

Infection in Patients with Spinal Cord Injury

Diagnosing a UTI in a patient with a spinal cord injury is difficult. In patients with SCI, signs
and symptoms suggestive of a UTI are malodorous and cloudy urine, muscular spasticity,
fatigue, fevers, chills, and autonomic instability.
In these patients, suprapubic aspiration of the bladder is the criterion standard for diagnosing
a UTI, although it is not performed often in clinical practice.

For more information on this topic, see the Medscape Reference article Urinary Tract
Infections in Patients with Spinal Cord Injury.

Infection in Patients with Diabetes Mellitus

Patients with diabetes are at risk for complicated UTIs, which may include renal and
perirenal abscess, emphysematous pyelonephritis, emphysematous cystitis, fungal infections,
xanthogranulomatous pyelonephritis, and papillary necrosis.

For more information, see the Medscape Reference topic Urinary Tract Infections in Diabetes
Mellitus.

Cystitis Caused by Candida

Cystitis caused by Candida is clinically similar to cystitis from other pathogens. The presence
of fungus in the urine should be verified by repeating the urinalysis and urine culture. Other
features of diagnosis are as follows[19] :

 Pyuria is a nonspecific finding

 C glabrata may be differentiated from other species by morphology
 Candida casts in the urine indicate renal candidiasis but are rarely seen
 Colony counts have not proved diagnostically useful

Ultrasonography of the kidneys and collecting systems is the preferred initial study in
symptomatic or critically ill patients with candiduria, but computed tomography is better for
detecting pyelonephritis or perinephric abscess.[19]

Approach Considerations
Appropriate antibiotic treatment leads to significantly higher symptomatic and bacteriologic
cure rates and better prevention of reinfection in women with uncomplicated cystitis.[20]
Unfortunately, treatment also selects for antibiotic resistance in uropathogens and commensal
bacteria and has adverse effects on the gut and vaginal flora.[21]

Consequently, evolving practice seeks to achieve good symptom control for uncomplicated
acute cystitis while reducing antibiotic use. For example, European practice increasingly
includes the option of offering a 48-hour delayed antibiotic prescription to be used at the
patient's discretion.[22]

The first-choice agents for treatment of uncomplicated acute cystitis in women include
nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole (TMP-SMX), or
fosfomycin. Beta-lactam antibiotics may be used when other recommended agents cannot be
used.[23, 24] Fosfomycin and nitrofurantoin monohydrate/macrocrystals should be avoided in
patients with possible early pyelonephritis.[23] Fluoroquinolones are typically reserved for
complicated cystitis.
Empiric antibiotic selection is determined in part by local resistance patterns. In addition,
clinicians may wish to limit use of TMP-SMX in order to reduce the emergence of resistant
organisms.

Resistance to TMP-SMX has been associated with concomitant resistance to other antibiotics.
Because of the importance of maintaining the effectiveness of TMP-SMX for treatment of
serious infections, German national guidelines no longer recommend this agent as first-line
empiric treatment for uncomplicated cystitis.[24]

On average, women with cystitis who receive effective antibiotic treatment experience severe
symptoms for somewhat longer than 3 days.[10] Complete resolution of symptoms may require
approximately 6 days. Features that have been associated with a more prolonged course
include a history of somatization, previous cystitis, urinary frequency, and more severe
symptoms at baseline.[10] Patients who respond to antibiotics do not require follow-up urine
cultures.

Without treatment, 25-42% of uncomplicated acute cystitis cases in women will resolve
spontaneously.[20] Even without effective treatment, the likelihood that uncomplicated acute
cystitis will progress to pyelonephritis is only around 2%.[25]

German investigators reported that symptomatic treatment with ibuprofen (400 mg 3 times
daily) did not prove to be inferior to antibiotic treatment with ciprofloxacin.[26] This
randomized, controlled pilot trial in 79 women with uncomplicated acute cystitis found no
significant difference in symptom resolution between the 2 groups. A notable but statistically
insignificant difference was that 33.3% of patients in the ibuprofen group and 18% in the
ciprofloxacin group required secondary antibiotic treatment.

Patient disposition

With few exceptions, the vast majority of women with urinary tract infection (UTI) present
on an ambulatory basis and can be treated as outpatients. Exceptions include
immunocompromised or elderly patients who have a UTI manifesting as a sepsis syndrome
with circulatory insufficiency. In this situation, mental status changes (eg, confusion) or
profound weakness may prompt paramedical transport to the hospital. Patients with
hypotension, tachycardia, and delayed capillary refill require intravenous (IV) fluid
resuscitation in the field.

Hospital admission may be indicated for some patients with complicated UTI. Complicating
factors include the following:

 Structural abnormalities (eg, calculi, tract anomalies, indwelling catheter, obstruction)

 Metabolic disease (eg, diabetes, renal insufficiency)
 Impaired host defenses (eg, HIV, current chemotherapy, underlying active cancer)

Adequate fluid resuscitation restores effective circulating volume and generous urinary
volumes. Antipyretic pain medications may be administered, as appropriate.

Uncomplicated Cystitis in Nonpregnant Patients

Uncomplicated cystitis occurs in patients who have a normal, unobstructed genitourinary
tract; who have no history of recent instrumentation; and whose symptoms are confined to the
lower urinary tract. Uncomplicated cystitis is most common in young, sexually active
women. Patients usually present with dysuria, urinary frequency, urinary urgency, and/or
suprapubic pain. Treatment regimens for uncomplicated cystitis in nonpregnant women are
provided in Table 1, below.

Table 1. Treatment Regimens for Uncomplicated Cystitis in Nonpregnant Women[23] (Open

Table in a new window)

First-line therapy
 trimethoprim/sulfamethoxazole* 160 mg/800 mg (Bactrim DS, Septra DS) 1 tablet PO
BID for 3d (use when bacterial resistance is < 20% and patient has no allergy) or
 nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg PO BID for 5-7d or
 nitrofurantoin macrocrystals (Macrodantin) 50-100 mg PO QID for 7d or
 fosfomycin (Monurol) 3 g PO as a single dose with 3-4 oz of water

Second-line therapy
 ciprofloxacin (Cipro) 250 mg PO BID for 3d or
 ciprofloxacin extended release (Cipro XR) 500 mg PO daily for 3d or
 levofloxacin (Levaquin) 250 mg PO q24h for 3d or
 ofloxacin 200 mg PO q12h for 3d

Alternative therapy
 amoxicillin-clavulanate (Augmentin) 500 mg/125 mg PO BID for 3-7d or
 amoxicillin-clavulanate (Augmentin) 250 mg/125 mg PO TID for 3-7d or
 cefdinir 300 mg PO BID for 7d or
 cefaclor 500 mg PO TID for 7d or
 cefpodoxime 100 mg PO BID for 7d or
 cefuroxime 250 mg PO BID for 7-10d

*Should generally be avoided in elderly patients because of the risk of affecting renal
function.

Complicated Cystitis in Nonpregnant Women

Complicated cystitis is associated with an underlying condition that increases the risk of
therapeutic failure. Some underlying conditions include diabetes, symptoms for 7 days or
longer before seeking care, renal failure, functional or anatomic abnormality of the urinary
tract, renal transplantation, an indwelling catheter stent, or immunosuppression. Treatment
regimens for complicated cystitis in nonpregnant women are provided in Table 2, below.

Table 2. Treatment Regimens for Complicated Cystitis in Nonpregnant Women[13] (Open

Table in a new window)

First-line therapy
Oral:
Patients with complicated cystitis who can tolerate oral therapy may be treated with the
following options:

 ciprofloxacin (Cipro) 500 mg PO BID for 7-14d or

 ciprofloxacin extended release (Cipro XR) 1 g PO daily for 7-14d or
 levofloxacin (Levaquin) 750 mg PO daily for 5d

Parenteral:

Patients who cannot tolerate oral therapy as outlined above or patients with infection that is
suspected to be due to resistant organisms should be treated with parenteral therapy, as
follows:

 ciprofloxacin (Cipro) 400 mg IV q12h for 7-14d or

 levofloxacin (Levaquin) 750 mg IV daily for 5d or
 ampicillin 1-2 g IV q6h plus gentamicin 2 mg/kg/dose q8h for 7-14d or
 piperacillin-tazobactam (Zosyn) 3.375 g IV q6h or
 doripenem 500 mg (Doribax) IV q8h for 10d or
 imipenem-cilastatin (Primaxin) 500 mg IV q6h for 7-14d or
 meropenem (Merrem) 1 g IV q8h for 7-14d

Duration of therapy: shorter courses (7d) are reasonable if patient improves rapidly; longer
courses (10-14d) are reasonable if patient has a delayed response or is hospitalized.

Parenteral therapy can be switched to oral therapy once clinical improvement is observed.

Second-line therapy
 cefepime (Maxipime) 2 g IV q12h for 10d or
 ceftazidime (Fortaz, Tazicef) 500 mg IV or IM q8-12h for 7-14d

Duration of therapy: shorter courses (7d) are reasonable if patient improves rapidly; longer
courses (10-14d) are reasonable if patient has a delayed response or is hospitalized.

Parenteral therapy can be switched to oral therapy once clinical improvement is observed.
Antimicrobial Therapy
Oral therapy with an antibiotic effective against gram-negative aerobic coliform bacteria,
such as E coli, is the principal treatment intervention in patients with lower urinary tract
infections.

For women with acute bacterial cystitis who are otherwise healthy and not pregnant, 3 days
of therapy with most antimicrobial agents is generally more effective than single-dose
therapy and as effective as the same drug administered for a longer duration. Exceptions are
nitrofurantoin monohydrate/macrocrystals and beta-lactams as a group. Cystitis in older
women or infection caused by Staphylococcus saprophyticus is less responsive to 3 days of
therapy; therefore, 7 days of therapy is suggested.

The 2010 Infectious Disease Society of America (IDSA) guidelines for uncomplicated
cystitis in nonpregnant patients recommend nitrofurantoin monohydrate/macrocrystals
(Macrobid, 100 mg orally twice daily for 5-7 days) or nitrofurantoin macrocrystals
(Macrodantin, 50 -100 mg orally 4 times daily for 7 days). Efficacy is comparable to 3 days
of trimethoprim-sulfamethoxazole (TMP-SMX).[23]

IDSA guidelines recommend TMP-SMX (160 mg/800 mg [1 double-strength tablet] orally

given twice daily for 3 days) as an appropriate choice for treatment of acute uncomplicated
cystitis if local resistance rates of uropathogens do not exceed 20% or if the infecting strain is
known to be susceptible. TMP-SMX should not be used empirically if the patient has
received this agent for treatment of UTI during the previous 3 months.[23]

Nitrofurantoin monohydrate/macrocrystals has the advantage of taking resistance pressure off

the much-used quinolone class. In a 2009 analysis by Olson et al, 29.6% of 176 urinary
isolates with E coli studied were resistant to TMP-SMX; none was resistant to nitrofurantoin
macrocrystals. Resistance to ciprofloxacin was 1.8% in first-time UTIs, versus 11.8% in
recurrent UTIs. The authors recommended considering nitrofurantoin as a first-line agent for
uncomplicated lower UTIs.[27]

Similarly, a decision and cost analysis by McKinnell et al found that nitrofurantoin

minimized cost when the prevalence of fluoroquinolone resistance exceeded 12% or the
prevalence of TMP-SMX resistance exceeded 17%.[28] On the basis of efficacy, cost, and low
impact on promoting antimicrobial resistance, these researchers recommended that clinicians
consider nitrofurantoin as a reasonable alternative to TMP-SMX and fluoroquinolones for
first-line therapy for uncomplicated UTIs.

Fosfomycin (a single dose of 3 g with 3-4 oz of water) is also an appropriate choice for
therapy, where available, because of minimal resistance and propensity for collateral damage.
Fosfomycin is approved by the US Food and Drug Administration (FDA) for single-dose
treatment in adult women with uncomplicated UTI caused by Escherichia coli or
Enterococcus faecalis.
It has been reported that the efficacy of single-dose fosfomycin is inferior to that of standard
short-course regimens.[23] However, a recent meta-analysis of 27 trials found no difference in
efficacy between fosfomycin and other antibiotics for treatment of cystitis and found that
fosfomycin was associated with significantly fewer adverse reactions in pregnant women.[29]

Fluoroquinolones (eg, ofloxacin, ciprofloxacin, levofloxacin) are highly effective in UTIs,

but these agents have a propensity for causing collateral damage and should be reserved for
important uses other than acute uncomplicated cystitis.[23] IDSA guidelines recommend that
fluoroquinolones be used as second-line agents for acute uncomplicated cystitis and as first-
line oral therapy for complicated cystitis.

According to the IDSA guidelines, beta-lactam agents (eg, amoxicillin-clavulanate, cefdinir,

cefaclor, cefpodoxime-proxetil) in 3–7-day regimens are appropriate second-line choices
when other recommended agents cannot be used. The IDSA advises against using amoxicillin
or ampicillin for empiric treatment, because these agents have relatively poor efficacy and
high rates of resistance.[23]

Adjunctive Therapy
Patients with intense dysuria may obtain symptomatic relief from a bladder analgesic, such as
phenazopyridine, to be used for 1-2 days. Do not prescribe phenazopyridine if the patient has
a sulfa allergy. Avoid long-term use, as this agent may mask symptoms of therapeutic failure
or recurrence. Many authors advise stressing the intake of plenty of fluids to promote a dilute
urine flow.

Fungal Infection
In catheterized patients, removal of the catheter is essential for clearance of funguria. If the
catheter is still needed, replace it (preferably a day later).

Treatment options vary from topical treatment to systemic therapy. A regimen of

amphotericin-B bladder washes for 7 days provides a prompt but nonsustained response. It
does not treat systemic mycoses and is inconvenient to administer. Amphotericin B, 0.3
mg/kg IV for 1 dose, is an option that provides a more sustained and systemic response.

Fluconazole 200 mg orally, followed on subsequent days by 100 mg orally once a day for 4-7
days, is a simpler option. This drug is effective against azole-responsive Candida organisms.
Generally, azole resistance is observed only in C krusei and C glabrata. Fluconazole provides
a good long-term effect but takes a few days to clear the urine.

Patients with Spinal Cord Injury

Once a urethral catheter is in place, the daily incidence of bacteriuria is 3-10%. Antibiotics
should be reserved for patients with clear signs and symptoms of UTI. In these patients,
suprapubic aspiration of the bladder is the criterion standard for diagnosing a UTI, although it
is not performed often in clinical practice.
Oral fluoroquinolones are the drugs of choice for empiric treatment of acute UTIs. However,
these drugs have a propensity for collateral damage and should be reserved for important uses
other than acute cystitis.

For more information on this topic, see the Medscape Reference article Urinary Tract
Infections in Patients with Spinal Cord Injury.

Pregnant Patients
The physiologic changes associated with pregnancy increase the risk of serious infectious
complications from symptomatic and asymptomatic urinary tract infections even in healthy
pregnant women. Consequently, treatment is indicated for pregnant women with
asymptomatic bacteriuria, as well as for those with symptomatic UTIs; antibiotic selection
may differ, and regimens are typically more prolonged.

For more information, see the Medscape Reference topic Urinary Tract Infections in
Pregnancy.

Renal Transplantation Patients

Treatment of UTIs in renal transplant patients is preferably with a fluoroquinolone. TMP-
SMX poses the risk of inducing renal failure in the transplanted kidney and consequently
should be avoided unless the patient’s creatinine clearance is normal.

Asymptomatic bacteriuria should be treated for 10 days. Parenteral antibiotics should be used
for severe infections. The duration of antibiotics for severe infections is 4-6 weeks.

Asymptomatic Bacteriuria
In most patient populations, asymptomatic bacteriuria has not been shown to be harmful.
Furthermore, although persons with bacteriuria are at increased risk of symptomatic urinary
tractions, treatment of asymptomatic bacteriuria does not decrease the frequency of
symptomatic infections or improve other outcomes. Consequently, screening for or treatment
of asymptomatic bacteriuria is not appropriate and should be discouraged.[30]

Asymptomatic bacteriuria in women should be treated only in pregnant patients, in patients

undergoing a urologic procedure that may produce mucosal bleeding, and in the significantly
immunosuppressed (eg, renal transplantation patients). It should not be treated in diabetic
persons, elderly individuals, and patients with indwelling catheters. Diabetic woman have a
high rate of asymptomatic bacteriuria with nonpathogenic strains, which can persist for long
periods without progressing to infection.[31]

For a full discussion of this topic, see the Medscape Reference article Asymptomatic
Bacteriuria.

Diet
Hydration to accentuate unidirectional clearance of bacteriuria is recommended, especially if
an obstruction was relieved recently. Drinking cranberry juice (10 oz/day) or taking cranberry
tablets may offer some benefit in reducing recurrent UTI and does not appear to be
harmful.[32, 33]

Cranberries contain type A proanthocyanidins. This compound and its urinary metabolites
interfere with the adhesiveness of uropathogenic bacteria to the bladder epithelium.[34] Their
effect is not as significant as antibiotics, but they do not induce bacterial resistance. Because
of their variable intestinal absorption, it is difficult to design a valid study comparing them
head-to-head with antimicrobials.[32]

Consultations
Urologic consultation is essential in patients with UTIs complicated by obstruction, renal
cysts, perinephric abscess, renal carbuncle, or unknown renal masses. Other consultations
depend on the patient's underlying state of health and may include an obstetrician,
gynecologist, endocrinologist, nephrologist, neurologist, or neurosurgeon. In patients who
present to the emergency department, consultation with the patient's primary care provider is
suggested.

In the patient with a complicated UTI, coverage for unusual or multiple antibiotic–resistant
organisms (eg, Pseudomonas aeruginosa) must be considered. An infectious disease
consultation may be helpful in selecting the appropriate antimicrobial agent. Infectious
disease input is essential for immunocompromised patients and those infected with unusual or
resistant pathogens. A pharmacokinetics consultation is suggested when using
aminoglycosides.

Prevention and Long-Term Monitoring

Prophylactic measures are indicated for patients with any of the following:

 Recurrent UTIs
 Spinal cord injury
 Urinary catheters
 Renal transplants

Sexually active women may attempt voiding immediately after intercourse to lessen the risk
of coitus-related introduction of bacteria into the bladder. Some authors recommend large
urinary flow volumes as a measure that will reduce the risk of UTI.

Prophylactic regimens for women with frequent recurrent UTIs include postcoital or
continuous antibiotics. Women with fewer than 3 UTIs per year may benefit from self-
initiated antibiotic therapy. For more information, see the Medscape Reference topic
Prevention of Urinary Tract Infections.

Medication Summary
The goals of pharmacotherapy are to eradicate the infection, prevent complications, and
provide symptomatic relief to patients. Early treatment is recommended to reduce the risk of
progression to pyelonephritis.

It is important to identify antimicrobial resistance patterns when considering empirical

antimicrobial selection. Oral therapy with an empirically chosen antibiotic that is effective
against gram-negative aerobic coliform bacteria, such as Escherichia coli, is the principal
treatment intervention in patients with lower urinary tract infections. Appropriate
antimicrobials for the treatment of cystitis include trimethoprim-sulfamethoxazole (TMP-
SMX), nitrofurantoin, fluoroquinolones, or cephalosporins. Some patients may require a
urinary analgesic such as oral phenazopyridine, which is useful to relieve discomfort due to
severe dysuria.

Sulfonamides
Class Summary

Sulfonamides inhibit bacterial dihydropteroate synthase by competing with para-

aminobenzoic acid (PABA). This action interferes with the uptake of PABA into folic acid,
an essential component of bacterial development.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Trimethoprim-sulfamethoxazole (TMP-SMX) is designed to take advantage of the synergy

between trimethoprim and sulfonamides. TMP-SMX activity includes common urinary tract
pathogens, both aerobic gram-positive and gram-negative bacteria, except Pseudomonas
aeruginosa. Empiric therapy with TMP-SMX should be avoided if the prevalence of
resistance is greater than 20%. This agent has been given an A-I rating in the 2010 Infectious
Disease Society of America (IDSA) guidelines for treating cystitis.[23] General dosing
recommendations include administering 1 tablet (160 mg/800 mg) twice a day for 3 days in
patients with uncomplicated cystitis.

Antibiotics, Other
Class Summary

Empiric antimicrobial therapy should cover all likely pathogens in the context of this clinical
setting. Antibiotics that have been used include nitrofurantoin, fosfomycin, or trimethoprim.

Nitrofurantoin (Furadantin, Macrobid, Macrodantin)

Nitrofurantoin is bacteriocidal in urine at therapeutic doses. It is indicated for the treatment of

cystitis when caused by susceptible strains of E coli, enterococci, Staphylococcus aureus, and
certain strains of Klebsiella and Enterobacter species. It is a good treatment option because of
minimal resistance and propensity for collateral damage.

This agent has been given an A-I rating in the 2010 Infectious Disease Society of America
(IDSA) guidelines for treating cystitis.[23] Nitrofurantoin should be avoided if there is
suspicion for early pyelonephritis, and it is contraindicated when creatinine clearance is less
than 60 mL/min.

Nitrofurantoin is manufactured in different forms to facilitate durable concentrations in the

urine: macrocrystals (Macrodantin) and microcrystal suspension (Furadantin). A combined
preparation of monohydrate/monocrystals (Macrobid) is indicated only for the treatment of
acute cystitis caused by susceptible strains of E coli or S saprophyticus in patients 12 years of
age and older.

General dosing recommendations for patients with uncomplicated cystitis include

nitrofurantoin monohydrate/macrocrystals, 100 mg twice a day for 5-7 days, or

nitrofurantoin macrocrystals, 50-100 mg 4 times a day for 7 days.

Fosfomycin (Monurol)

Fosfomycin is a bactericidal agent that is used for the treatment of uncomplicated cystitis in
susceptible strains of E coli and Enterococcus faecalis. Little cross-resistance between
fosfomycin and other antibacterial agents exists. It is primarily excreted unchanged in the
urine, and concentrations remain high for 24-48 hours after a single dose. This agent has been
given an A-I rating in the 2010 IDSA guidelines for treating cystitis.[23] Fosfomycin can be
administered at a dose of 3 g as a single dose with 3-4 oz of water for uncomplicated cystitis.

Trimethoprim (Primsol)

Trimethoprim inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. It is

active in vitro against a broad range of gram-positive and gram-negative bacteria, including
uropathogens, such as Enterobacteriaceae and S saprophyticus. Resistance usually is
mediated by decreased cell permeability or alterations in the amount or structure of
dihydrofolate reductase. It demonstrates synergy with the sulfonamides, potentiating the
inhibition of bacterial tetrahydrofolate production.

Fluoroquinolones
Class Summary

Fluoroquinolones are highly effective against gram-negative and gram-positive bacteria. A

major concern with fluoroquinolones is the development of resistance among uropathogens
and other organisms.[35] For that reason, these agents should be reserved as alternative
therapies for acute cystitis. Fluoroquinolones are effective in 3-day regimens. In the 2010
IDSA guidelines, quinolones have an A-III rating for treating cystitis.[23]

Ciprofloxacin (Cipro. Proquin XR)

Ciprofloxacin is used to treat cystitis that is caused by E coli or S saprophyticus. For acute
uncomplicated cystitis, the recommended dosage is 250 mg twice daily for 3 days. As the
severity of the condition worsens, the duration of therapy is extended.

Ofloxacin
Ofloxacin is indicated for the treatment of both uncomplicated and complicated cystitis. Like
other fluoroquinolones, it is most effective against gram-negative organisms such as E coli,
Citrobacter diversus, C freundii, Enterobacter cloacae, Klebsiella species, Proteus species,
and Shigella species. The usual regimen for uncomplicated cystitis is 200 mg given twice
daily for 3 days. Complicated cystitis can be treated for 10 days.

Levofloxacin (Levaquin)

Levofloxacin is indicated for the treatment of uncomplicated and complicated cystitis. It is

used to treat cystitis caused by E coli, S saprophyticus, or Klebsiella species. Levofloxacin
can be given for uncomplicated cystitis at a dose of 250 mg every 24 hours for 3 days. It can
also be given for complicated cystitis at a dose of 750 mg daily for 5 days or a dose of 250
mg daily for 10 days.

Penicillins, Amino
Class Summary

Penicillins such as amoxicillin and ampicillin are not recommended as empiric therapy for
uncomplicated cystitis. However, amoxicillin-clavulanate may be used in uncomplicated
cystitis as an alternative therapy.

Amoxicillin-clavulanate (Augmentin, Augmentin XR)

A beta-lactam antibiotic such as amoxicillin-clavulanate in 3-7 day regimens is recommended

for the treatment of uncomplicated cystitis when other agents are not appropriate. In the 2010
IDSA guidelines, amoxicillin-clavulanate has a B-I rating for treating cystitis.[23]

Ampicillin

Ampicillin has activity against anaerobes and gram-negative aerobes. Ampicillin can be
given intravenously or intramuscularly and is generally used in combination with an
aminoglycoside (gentamicin) for empiric or directed activity against E faecalis in patients
with complicated cystitis who cannot tolerate oral therapy or in patients in whom infection
with resistant organisms is suspected.

Cephalosporins, Second Generation

Class Summary

Cephalosporins represent the majority of antibiotics known as beta-lactam antibiotics. The

2010 IDSA guidelines for treating cystitis give beta-lactams, in general, a B-I rating, listing
them as second-line agents.[23] Cephalosporin antibiotics are classified into “generations” that
somewhat correspond to their spectrum of action.

Cefaclor
Cefaclor is indicated for the treatment of cystitis and pyelonephritis that is caused by E coli,
Proteus mirabilis, Klebsiella species, and coagulase-negative staphylococci. Cefaclor has
been used at a dose of 500 mg 3 times a day for 7 days in patients with uncomplicated
cystitis.

Cefuroxime (Ceftin, Zinacef)

Cefuroxime is indicated for the treatment of uncomplicated cystitis that is caused by E coli or
Klebsiella pneumoniae. The general dosing recommendation is 250 mg given twice daily for
7-10 days.

Cephalosporins, Third Generation

Class Summary

Third-generation cephalosporins are broad-spectrum and have bactericidal activity. These

drugs are the most active against serious gram-negative pathogens but have some activity
against gram-positive pathogens. The 2010 IDSA guidelines for treating cystitis give beta-
lactams, in general, a B-I rating, listing them as second-line agents.[23]

Cefpodoxime

Cefpodoxime is approved for the treatment of uncomplicated cystitis. It is an extended-

spectrum oral cephalosporin with bactericidal activity against a wide spectrum of gram-
positive and gram-negative bacteria, including E coli, S saprophyticus, and K pneumoniae.
Patients with uncomplicated cystitis can be treated with cefpodoxime, 100 mg twice a day for
7 days.

Cefdinir

Cefdinir has been used an alternative therapy for uncomplicated cystitis when other therapies
cannot be used. Dosing recommendations include 300 mg twice daily given for 7 days.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime has broad-spectrum gram-negative activity and lower efficacy against gram-
positive organisms. It is approved for both complicated and uncomplicated cystitis caused by
Pseudomonas aeruginosa; Enterobacter species; Proteus species, including P mirabilis and
indole-positive Proteus; Klebsiella species; and E coli. Ceftazidime, 500 mg IV or IM every
8-12 hours for 7-14 days, can be administered to patients with complicated cystitis. For
patients with uncomplicated cystitis, a dose of 250 mg IV or IM can be given every 12 hours.

Cephalosporins, Other
Class Summary

Cefepime is a fourth-generation drug that has the gram-negative activity of the third-
generation agents and the gram-positive activity of the first-generation drugs.
Cefepime (Maxipime)

Cefepime is a zwitterion; this property is thought to enhance the ability of this agent to
penetrate porin channels in the cell walls of gram-negative bacteria. Cefepime is ideal for
intramuscular administration.

Cefepime is indicated for the treatment of complicated and uncomplicated cystitis caused by
E coli or K pneumoniae when the infection is severe or caused by E coli, K pneumoniae, or P
mirabilis when the infection is mild to moderate, including cases associated with concurrent
bacteremia with these microorganisms. Cefepime can be administered at a dose of 2 g IV
every 12 hours for 10 days for patients with severe complicated cystitis.

Penicillins, Extended-Spectrum
Class Summary

Extended-spectrum penicillins have a broad spectrum of bactericidal activity. They are used
mainly in the treatment of infections suspected or known to be caused by gram-negative
aerobes.

Piperacillin-tazobactam (Zosyn)

Piperacillin-tazobactam is useful because of its broad spectrum of bactericidal activity against

gram-positive and gram-negative aerobic and anaerobic organisms. Piperacillin is a beta-
lactam antibiotic and is mainly bactericidal. Tazobactam is an irreversible inhibitor of
bacterial beta-lactamases.

Aminoglycosides
Class Summary

Aminoglycosides are bactericidal antibiotics used primarily in the treatment of gram-negative

infections. They irreversibly bind to the 30S subunit of bacterial ribosomes, blocking the
recognition step in protein synthesis and causing misreading of the genetic code. The
ribosomes separate from the messenger RNA; cell death ensues.

Gentamicin

Gentamicin has activity against various aerobic gram-negative bacteria, as well as E faecalis
and staphylococcal species. It is the only aminoglycoside with appreciable activity against
gram-positive organisms. Gentamicin is used with ampicillin to treat patients with
complicated cystitis who cannot tolerate oral therapy or patients in whom infection with
resistant organisms is suspected.

Analgesics, Urinary
Class Summary
These agents relieve pain, discomfort, and spasms of the bladder.

Phenazopyridine (Azo Standard, Azo Standard Maximum Strength,

Baridium, Pyridium, UTI Relief)

Phenazopyridine is an azo dye excreted in urine, where it exerts a topical analgesic effect on
urinary tract mucosa. It is compatible with antibacterial therapy and can help relieve pain and
discomfort before antibacterial therapy controls infection. Its analgesic action may reduce or
eliminate the need for systemic analgesics or narcotics.

Carbapenems
Class Summary

Carbapenem antibiotics are broad-spectrum antibiotics that are structurally related to beta-
lactam antibiotics. The bactericidal activity of carbapenems results from the inhibition of cell
wall synthesis and is mediated through the binding to penicillin-binding proteins (PBPs).
Parenteral therapy may be warranted for treatment of patients with complicated cystitis who
cannot tolerate oral therapy. Parenteral regimens that can be used include carbapenem
antibiotics.

Doripenem (Doribax)

Doripenem is indicated as a single agent for the treatment of complicated cystitis and
pyelonephritis caused by E coli (including cases with concurrent bacteremia), K pneumoniae,
P mirabilis, P aeruginosa, and Acinetobacter baumannii. The general dosing recommendation
is 500 mg IV every 8 hours for 10 days.

Imipenem/cilastatin (Primaxin)

Imipenem is a carbapenem antimicrobial agent. It is mainly bactericidal, and it inhibits the

third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs
that are located inside the bacterial cell wall.

Cilastatin is a reversible, competitive inhibitor of dehydropeptidase-1 (DHP-1), an enzyme

found in the brush border of the proximal tubular cells of the kidneys that breaks down
imipenem to inactive metabolites. Cilastatin prevents the renal metabolism of imipenem,
which results in an increase in urinary concentrations of imipenem and minimizes the
nephrotoxicity observed when imipenem is administered alone. Imipenem can be
administered at a dose of 500 mg IV every 6 hours for 7-14 days.

Meropenem (Merrem)

Meropenem is indicated for the treatment of bacterial meningitis, complicated skin and skin-
structure infections, and intra-abdominal infections. However, it can also be used for the
treatment of complicated cystitis. It inhibits cell wall formation, facilitates bacterial cell lysis,
and is primarily a bactericidal agent. It inhibits the third and final stage of bacterial cell wall
synthesis by preferentially binding to specific PBPs that are located inside the bacterial cell
wall.
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