URINARY TRACT

INFECTIONS
(UTI)

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 • UTI is an infection in any part of the
urinary system. The urinary tract
consists of the kidneys, ureters, bladder,
and urethra.

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 TYPES OF INFECTION
Classified anatomically as
• Upper UTI - Involves the kidney or ureter
– Acute pyelitis – infection of pelvis of
kidney
– Acute pyelonephritis – infection of the
parenchyma of the kidney
• Lower UTI – Urinary bladder downwards
– Urethritis – infection of urethra
– Cystitis – infection of the urinary bladder
– Prostatitis – infection of the prostate

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 PREDISPOSING FACTORS

• Age - incidence increases with age

• Pregnancy – dilatation of ureters
and renal pelvis, incompetence of
vesico-urethral valves, hormonal
changes

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 Sex:
• The anatomy of the female urethra is of
particular importance to the pathogenesis
of UTIs. The female urethra is relatively
short compared with the male urethra and
also lies in close proximity to the warm,
moist, perirectal region, which is teeming
with microorganisms.

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 • Because of the shorter urethra, bacteria can reach the
bladder more easily in the female host; thus urinary tract
infections are primarily a disorder in females.
• In males, the incidence of urinary tract infections
increases after the age of 60 years, when the
enlargement of the prostate interferes with the removal
of urine from the bladder.

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 PREDISPOSING FACTORS

• Structural and functional abnormality

–obstruction due to stricture, calculus,
tumour or prostatic hypertrophy
• Neurogenic bladder, vesico-urethral reflex
• Genital prolapse
• Intervention – catheterisation
• Bacterial virulence - pili

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 • Pathogenesis :
• Routes of Infection: Bacteria can invade and cause a UTI via three
major routes: ascending, hematogenous, and lymphatic
pathways. Although the ascending route is the most common cause
of infection in females, ascent in association with instrumentation
(e.g., urinary catheterization, cystoscopy) is the most common
cause of health care–associated UTIs in both sexes.

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 • For UTIs to occur by the ascending pathway, enteric
gram-negative bacteria and other microorganisms that
originate in the gastrointestinal tract must be able to
colonize the vaginal cavity or the periurethral area.
Once these organisms gain access to the bladder, they
may multiply and then pass up the ureters to the
kidneys.

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 • In most hospitalized patients, UTI is preceded by urinary catheterization or
other manipulation of the urinary tract.
• Soon after hospitalization, patients become colonized with bacteria
endemic to the institution, often gram-negative aerobic and facultative bacilli
carrying resistance markers. These bacteria colonize the patient’s skin,
gastrointestinal tract, and mucous membranes, including the anterior
urethra.

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 • With insertion of a catheter, the bacteria may be pushed along the
urethra into the bladder or, with an indwelling catheter, may migrate
along the track between the catheter and the urethral mucosa,
gaining access to the bladder. It is estimated that approximately
10% to 30% of catheterized patients will develop bacteriuria
(presence of bacteria in urine).

• UTIs may also occur by the hematogenous, or bloodborne route.

Hematogenous spread usually occurs as a result of bacteremia.

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 *Any systemic infection can lead to seeding of the kidney, but certain
organisms, such as Staphylococcus aureus or Salmonella spp., are
particularly invasive. Although most infections involving the kidneys
are acquired through the ascending route, yeast (usually Candida
albicans), Mycobacterium tuberculosis, Salmonella spp., Leptospira
spp., or S. aureus in the urine may indicate pyelonephritis acquired
via hematogenous spread, or the descending route.

• Increased pressure on the bladder can cause lymphatic flow into

the kidneys, resulting in UTI.

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 • The Host-Pathogen Relationship

• In most cases, the host defense mechanisms are able to

eliminate the organisms.

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 • In addition, if urine has a low pH, high or low osmolality, high urea
concentration, or high organic acid content, even organisms capable
of growth in the urinary tract may be inhibited.

• If bacteria do gain access to the bladder, the constant flushing of

contaminated urine from the body either eliminates bacteria or
maintains their numbers at low levels. Clearly, any interference with
the act of normal voiding, such as mechanical obstruction resulting
from kidney stones or strictures, will promote the development of
UTI.

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 • A valve-like mechanism at the junction of the ureter and bladder
prevents the reflux (backward flow) of urine from the bladder to the
upper urinary tract.
*Therefore if the function of these valves is inhibited or compromised in
any way, such as by obstruction or congenital abnormalities, urine
reflux provides a direct route for organisms to reach the kidney.
• Hormonal changes associated with pregnancy and their effects on
the urinary tract increase the chance for urine reflux to the upper
urinary tract.

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 *Activation of the host immune response by uropathogens also plays a
key role in fending off infection. For example, bacterial contact with
urothelial cells initiates an immune response via a variety of
signaling pathways. Bacterial lipopolysaccharide activates host cells
to ultimately release cytokines such as tumor necrosis factor and
interferon-gamma.

*In addition, bacteria can activate the complement cascade, leading to

the production of biologically active components such as opsonins,
as well as augment the host’s adaptive immune response.

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 • Host factors that lead to resistance to uropathogens have been
identified. For example, a glycoprotein synthesized exclusively by
epithelial cells in a specific anatomic location in the kidney, referred
to as Tamm-Horsfall protein (THP) or uromodulin, serves as an
antiadherence factor by binding to E. coli– expressing type 1
fimbriae.
• Defensins, a group of small antimicrobial peptides, are produced
by a variety of host cells such as macrophages, neutrophils, and
cells in the urinary tract and attach to the bacterial cell, eventually
causing the organism’s death.

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 • Although many microorganisms can cause UTIs, most
cases are a result of infection by a few organisms. To
illustrate, only a limited number of serogroups of E. coli
cause a significant proportion of UTIs.
• Uropathogenic E. coli (UPEC) possesses virulence
factors that enhance their ability to colonize and invade
the urinary tract. Those virulence factors are,
 Type 1 fimbriae that bind to uroepithelial cells
 Type P fimbriae that recognize kidney glycosphingolipids
 Siderophores that help gather iron from the host
 Alpha and beta-hemolysins that lyse host erythrocytes
 Capsules (K antigens)
 Sat protein that acts as a proteolytic toxin
 Cytotoxic necrotizing factor (CNF)

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 • Genome sequences of some UPEC strains have been
determined, indicating that several potential virulence
factor genes associated with the acquisition and
development of UTIs are encoded on pathogenicity
islands (e.g., hemolysins and E. coli P fimbriae). By
definition, pathogenicity islands contain genes that are
associated with virulence and are absent from avirulent
(not typically found in fecal strains) or less virulent
strains of the same species. UPEC strains are a major
cause of community-acquired UTIs.

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 *The importance of adherence in the pathogenesis of UTIs
has also been demonstrated with other species of
bacteria. Once introduced into the urinary tract, Proteus
strains appear to be uniquely suited to cause significant
disease in the urinary tract. Data indicate that these
strains are able to facilitate their adherence to the
mucosa of kidneys. Also, Proteus is able to hydrolyze
urea via urease production. The species Proteus
mirabilis accounts for approximately 77% of the urinary
isolates. Hydrolysis of urea results in an increase in urine
pH that is directly toxic to kidney cells and also
stimulates the formation of kidney stones.

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 • Other bacterial characteristics may be important in the pathogenesis
of UTIs. Motility may be important for organisms to ascend to the
upper urinary tract against the flow of urine and cause
pyelonephritis. Some organisms demonstrate greater production of
capsular K antigen; this antigen protects bacteria from being
phagocytized.

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 Clinical Manifestations

• Sometimes UTIs are classified as uncomplicated or

complicated. Uncomplicated infections occur primarily in
otherwise healthy females and occasionally in male
infants and adolescent and adult males. Most
uncomplicated infections respond readily to antibiotic
agents to which the etiologic agent is susceptible.

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 • Complicated infections occur in both sexes. In general, individuals
who develop complicated infections often have certain risk factors.
 Underlying diseases that predispose the kidney to infection (e.g.,
diabetes, sickle cell anemia)
 Kidney stones
 Structural or functional abnormalities of the urinary tract (e.g., a
tipped bladder)
 Indwelling urinary catheters
• In general, complicated infections are more difficult to treat and
have greater morbidity (e.g., kidney damage, bacteremia) and
mortality compared with uncomplicated infections. Urinary tract
infections identified in pregnant women, men, children, and
hospitalized patients or patients in other health care–associated
settings (e.g., cancer outpatient clinics) may be considered
complicated infections.

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 • The clinical presentation of UTIs may vary, ranging from
asymptomatic infection to pyelonephritis. Some UTI
symptoms may be nonspecific, and the symptoms of
lower UTIs may be considerably similar to those of upper
UTIs.

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 • Asymptomatic bacteriuria - 5-7% of
pregnant women
• Undetected - untreated – symptomatic
infection - pyelonephritis –
• hypertension in pregnancy- Fetus
prematurity and perinatal death.

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 CLINICAL PRESENTATION

Symptomatic UTI
• Urgency, frequency, discomfort or pain
• Pyelonephritis – loin pain, tenderness, high
fever and rigor
• Cystitis – dysuria, fever with chills and
frequency
• Upper UTI – fever, flank pain

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 • Urethritis
Symptoms associated with urethritis (infection of the
urethra), dysuria (painful or difficult urination) and frequency,
are similar to those associated with other lower
UTIs. Urethritis is a common infection. Because C. trachomatis,
Neisseria gonorrhoeae, and T. vaginalis are common
causes of urethritis and considered to be sexually transmitted,

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 • Ureteritis
Inflammation or infection within the ureters (ureteritis) is
considered in combination with kidney infections. UTI
within the ureters indicates that organisms have begun or
are in the process of ascending into the kidneys

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 • Cystitis
Typically, patients with cystitis (infection of the bladder)
complain of dysuria, frequency, and urgency (compelling
need to urinate). These symptoms are a result not only of
inflammation of the bladder but also of multiplication of
bacteria in the urine and urethra. Often, there is tenderness
and pain over the area of the bladder. In some individuals,
the urine is grossly bloody. The patient may note urine
cloudiness and a bad odor. Because cystitis is a localized infection,
fever and other signs of a systemic illness are usually
not present.

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 • Pyelonephritis
Pyelonephritis refers to inflammation of the kidney parenchyma,
calices (cup-shaped division of the renal pelvis), and
pelvis (upper end of the ureter that is located inside the kidney)
and is usually caused by bacterial infection.
An inflammatory infiltrate of white blood cells,
predominantly lymphocytes, is typically present. In addition,
the tubules in the kidneys may either be dilated or
constricted and contain colloid casts (crystalized mucous
secretions). The typical clinical presentation of an upper urinary
tract infection includes fever and flank (lower back)
pain and, frequently, lower tract symptoms (frequency, urgency,
and dysuria). Patients can also exhibit systemic signs
of infection such as vomiting, diarrhea, chills, increased
heart rate, and lower abdominal pain.
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 • Acute Urethral Syndrome
Another UTI is acute urethral syndrome. Patients with
this syndrome are primarily young, sexually active females,
who experience dysuria, frequency, and urgency but yield
fewer organisms than 105 colony-forming units of bacteria
per milliliter (CFU/mL) urine on culture. Approximately
90% of these females have pyuria and 50% have symptoms
of acute cystitis

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 Urosepsis
Approximately 25% of sepsis cases (severe blood infection)
are a result of urosepsis, a systemic infection that may develop
from community-, hospital- or health care–associated
UTIs. Urosepsis is defined as evidence of a UTI and two or
more additional signs including an elevated temperature
(.38°C), an elevated heart rate (.90 beats per minute), an
increased respiratory rate (.20 breaths per minute or a
PCO2 of ,32 mm Hg), or an abnormal white blood cell
count (.12,000/mm3, ,4000/mm3, or .10% neutrophilic
band forms).

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 • Asymptomatic Bacteriuria
Asymptomatic bacteriuria or asymptomatic UTI is the
isolation of a specified quantitative count of bacteria in
an appropriately collected urine specimen obtained from
a person without symptoms or signs of urinary infection.
screening and treatment for asymptomatic bacteriuria is
recommended for pregnant females (because of the risk
of progression to severe symptomatic UTI and possible
harm to the fetus), males undergoing transurethral
resection of the prostate, and individuals undergoing
urologic procedures for which mucosal bleeding is
anticipated..
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 ETIOLOGY - BACTERIA
Etiological agents of urinary tract infection

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 • Miscellaneous Other less commonly isolated agents are:
 Acinetobacter and Alcaligenes spp., other Pseudomonas spp.,
Citrobacter spp., Gardnerella vaginalis, Aerococcus urinae, and
beta-hemolytic streptococci.
 Bacteria such as mycobacteria (predominantly in patients who are
human immunodeficiency virus [HIV]-positive), Chlamydia
trachomatis, Ureaplasma urealyticum, Mycoplasma hominis,
Campylobacter spp., Haemophilus influenzae, Leptospira, and
certain Corynebacterium spp. (e.g., C. renale) are rarely recovered
from urine

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 LABORATORY DIAGNOSIS
COLLECTION AND TRANSPORT OF SPECIMEN

• Specimen Collection : Prevention of contamination by

normal vaginal, perineal, and anterior urethral microbiota is the most
important consideration for collection of a clinically relevant urine
specimen.
• Samples collected:
• Midstream urine (MSU)
• Catheter sample urine (CSU)
• Suprapubic aspirate
• Early morning urine (EMU)

• If delay in processing, Preservative

used:1.8% boric acid
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 collecting, transporting, and processing
urinary tract specimens.

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 TYPES OF URINE SAMPLE
Specimen Collection
URINE

Male
MSU
Female

CSU During cystoscopy

Children, infants,
Suprapubic aspirate
older women

EMU TB of urinary tract

Initial flow Urethritis, prostatitis

Types of urine samples to be collected

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 • Clean-Catch Midstream Urine
The least invasive and preferred routine collection procedure,
the clean-catch midstream urine specimen collection,
must be performed carefully for optimal results, especially
with female patients.
• The patient should be instructed to wash their hands before cleaning the
periurethral area, wiping from front to back three times, each time with a
clean sterile gauze pad soaked with a mild detergent to prevent
contamination. Of importance, the patient should also be instructed to rinse
well with two or more sponges soaked in sterile distilled water to remove the
detergent, which may be bacteriostatic. Once cleansing is completed, the
patient should retract the labial folds or glans penis, begin to void, and then
collect a midstream urine sample.

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 • Straight Catheterized Urine
Although slightly more invasive, urinary catheterization
provides a method for the collection of uncontaminated
urine from the bladder in uncooperative patients or
patients
unable to void because of other underlying physiologic
conditions. Either a physician or another trained health
professional performs this procedure.

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 • Suprapubic Bladder Aspiration
After preparation of the skin, urine is withdrawn directly
into a syringe through a percutaneously inserted needle
during suprapubic bladder aspiration, thereby ensuring
a contamination-free specimen. The bladder must be full
before the procedure is performed. This collection
technique may be indicated in certain clinical situations,
such as pediatric practice, when urine is difficult to
obtain.

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 • Specimen Transport :
 Because it is an excellent supportive medium for growth
of most bacteria, urine must be immediately refrigerated
or preserved. Bacterial counts in refrigerated (4°C) urine
remain constant for as long as 24 hours.
 Urine transport tubes (BD Urine Culture Kit) containing
boric acid, sodium borate, and sodium formate have
been shown to preserve bacteria without refrigeration for
as long as 48 hours.

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 Approach to diagnosis
of urinary tract
infections
Urinary tract infections

Pus cells, RBCs,

bacteria
Microscopy
Gram stain

Quantitative methods
Culture
Semi-quantitative
methods
Antibiotic sensitivity

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 • Gram or Methylene Blue Stain :
• A differential Gram stain or basic nondifferential methylene blue
stain of urine is an easy, inexpensive means to provide immediate
information as to the nature of the infecting organism (bacteria or
yeast) to guide empiric therapy.
• After a drop of well-mixed urine is allowed to air dry, the smear is
fixed, stained, and examined under oil immersion for the presence
of 1 or 5 bacteria per oil immersion field (OIF).

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 • Red blood cells or erythrocytes identified in the urine,
hematuria, may also indicate UTI, but this occurs in a
variety of other physiologic disorders. White blood cell
casts in urine are strong evidence of pyelonephritis but
can also be associated with renal disease in the absence
of infection

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 • Pyuria
Pyuria (10 leukocytes/mm3, using a hematocytometer from
a clean catch midstream specimen) is the hallmark of
inflammation, and the presence of polymorphonuclear
neutrophils (PMNs) can be detected and enumerated in
uncentrifuged specimens.

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 • Indirect Indices: Screening tests commonly detect
bacteriuria or pyuria by examining for the presence of
bacterial enzymes or PMN enzymes rather than the
organisms or PMNs themselves.
• Griess nitrate test
• Catalase test
• Leukocyte Esterase Test

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 • Nitrate Reductase (Greiss) Test
The nitrate reductase (Greiss) test looks for the presence of urinary
nitrite, an indicator of UTI. Nitrate-reducing enzymes
that are produced by the most common urinary tract
pathogens reduce nitrate to nitrite. This test has been incorporated
onto a urinary dipstick that also tests for leukocyte
esterase, an enzyme produced by PMNs.

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 • Leukocyte Esterase Test
Evidence of a host response to infection is the presence of PMNs in
the urine. Because inflammatory cells produce leukocyte esterase, a
simple, inexpensive, and rapid method that measures this enzyme
has been developed. Studies have shown that leukocyte esterase
activity correlates with hemocytometer chamber counts. The nitrate
reductase and leukocyte esterase tests have been incorporated into
the urinary dipstick.

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 • Leukocyte Esterase Test
As previously mentioned, evidence of a host response to infection
is the presence of PMNs in the urine. Because inflammatory
cells produce leukocyte esterase, a simple, inexpensive,
and rapid method that measures this enzyme has been
Developed .
The nitrate reductase and leukocyte esterase tests have been
incorporated into the urinary dipstick.

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 • Catalase
The Accutest Uriscreen (JANT Pharmacal Crop., Encino,
CA) is another rapid urine-screening system based on the detection of
catalase present in human somatic cells and in
most bacterial species that commonly cause UTIs except for
streptococci and enterococci. Approximately 1.5 to 2 mL of
urine is added to a tube containing dehydrated substrate.
Hydrogen peroxide is added to the urine, and the solution
is mixed gently. The formation of bubbles above the liquid
surface is interpreted as a positive test.

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 • Automated and Semiautomated Systems
Various automated or semiautomated urine-screening
systems are commercially available, such as the Iris Urinalysis
System (Beckman-Coulter, Inc., Brea, CA), and
are capable of analyzing a urine or body fluid sample
in one instrument. The instrument analyzes both the
microscopic components and the urine chemistries by
combining technology of both types of analyzers into one
automated system.

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 • Urine Culture
Inoculation and Incubation of Urine Cultures. The urine should be
mixed thoroughly before plating. The plates can be inoculated using
a calibrated loop designed to deliver a known volume, either 0.01 or
0.001 mL of urine.

The calibrated loop that delivers the larger volume of urine (0.01 mL) is
recommended to detect lower numbers of organisms in certain
specimens. For example, urine collected from catheterization,
nephrostomies, ileal conduits, and suprapubic aspirates should be
plated with the larger calibrated loop.

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 Method for streaking with calibrated urine loop to
produce isolated colonies and countable colony-forming units .

Loop is touched to the center of the plate, from

which the inoculum is spread in a line across
the diameter of the plate.

Without flaming or re entering urine, loop is

drawn across the entire plate, crossing the first
inoculum streak numerous times to produce isolated
colonies.

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 The use of a 5% sheep blood agar plate and a MacConkey agar
plate allows detection of most gram-negative bacilli, staphylococci,
streptococci, and enterococci.

**To save cost and somewhat streamline culture processing, many

laboratories use an agar plate split in half (biplate); one side
contains 5% sheep blood agar and the other half contains
MacConkey or Eosin Methylene Blue agar.

• CLED agar does not contain sodium chloride, inhibiting the

characteristic swarming of Proteus spp., but still supports adequate
growth of most common urinary pathogens .

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 Before inoculation, urine is mixed thoroughly, and the top of the
container is then removed. The calibrated loop is inserted vertically
into the urine in a cup. Once plated, urine cultures are incubated
overnight at 37°C. Incubation for a minimum of 24 hours is typically
to detect uropathogens.
Interpretation of Urine Cultures
As previously mentioned, UTIs may be completely asymptomatic,
produce mild symptoms, or cause life-threatening infections. Of
importance, the criteria most useful for microbiologic assessment of
urine specimens is dependent not only on the type of urine
submitted (e.g., voided, straight catheterization) but the clinical
history of the patient (e.g., age, sex, symptoms, antibiotic therapy).

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 • One major problem in interpreting urine cultures arises
because urine cultures collected by the voided technique may be
contaminated with normal microbiota, including Enterobacteriaceae.
Determining what colony count represents true infection from
contamination is of utmost importance and is related to the patient’s
clinical presentation.
• A pure culture of S. aureus is considered to be significant regardless
of the number of CFUs, and antimicrobial susceptibility tests are
performed. The presence of yeast in any number is reported to
physicians, and pure cultures of yeast may be
identified to the species level.

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 • Kass concept of significant bacteriuria: the presence of bacteria
>105 CFU/ml of urine sample is considered significant.

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 An antibiotic sensitivity test should be preceded by a positive urine
culture . Antibiotic susceptibility test identifies which antibiotics the
bacteria is sensitive or resistant.
• Treatment
Antibiotics usually are the first treatment for urinary tract infections
Medicines commonly used for simple UTIs include:
• Trimethoprim and sulfamethoxazole
• Fosfomycin
• Nitrofurantoin
• Cephalexin
• Ceftriaxone

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 • The group of antibiotics known as fluoroquinolones isn't commonly
recommended for simple UTIs. These drugs include ciprofloxacin
(Cipro), levofloxacin and others ; which is recommended for
complicated UTI.

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