Urinary Tract Infection

Definition of UTI
UTIs are defined by the presence of micro

organisms within the urinary tract that

may be difficult to distinguish between
contamination, colonisation or infection.
Significant bacteriuria : > 10 5 cfu/ml
Covert bacteriuria : no symptom
Symptomatic bacteriuria : w/ symptoms

Definition

Women:

Presence of at least 100,000 colonyforming units (cfu)/mL in a pure

culture of voided clean-catch urine

Men:

Presence of just 1,000 cfu/mL

indicates urinary tract infection

*Some labs do not routinely identify & determine the

sensitivity of organisms for specimens with <10,000
cfu/mL. May have to special request.
Swart, Soler & Holman, 2004

Epidemiology of UTI
1%-6% of general practitioner visits are for UTIs.

150 million people per year become infected

UTI is more common in females.

(1-2% of young nonpregnant women)

40% of females will have a symptomatic UTI

in their life time.

In men: prevalence is 0.04%.
Incidence of UTI increases in old age.

(10% of men & 20% of women)

Importance of Urinary Tract Infections is

demonstrated by the fact that 20% of women

between ages 20-65 suffer one attack per year

Approximately 50% of women develop a UTI

during their lives and there is a prevalence rate

of 5% per year of asymptomatic or covert
bacteriuria in non-pregnant women between
ages 21 and 65

Amongst working women days lost from work

as a result of UTIs account for about one tenth

those due to respiratory infections .

Financial Statistics
The cost of hospitalization for UTI amounts

to $180 million annually.

True financial burden is much higher as it
includes
cost of outpatient services
Imaging
other diagnostic evaluations
long term complications
management of associated conditions that

increase the frequency and morbidity of UTI.

Prevalence
Community-dwelling
Long-term

elders 25%

care elders
(chronically bacteriuric)

Marked

Swart, Soler & Holman, 2004

25-50% of women
15-40% of men
Juthani-Mehta et al., 2005

increases in women & men after age 65

Wagenlehner, Naber & Weidner, 2005

Physiologic changes with aging in the urinary tract

Age-Related Changes
Decreased bladder capacity and increased
urine production (especially at night)
Decreased voided volume

Men

Women

Decreased estrogen w/menopause leads to

thinning of vaginal & urethral mucosa

Decreased lower urinary tract sensory

threshold

Palmer, 2004

Physiologic changes with aging in the urinary tract

Age-Related Changes

Men Women

Problems of urinary storage & emptying

incidence of overflow incontinence from

urethral obstruction or stricture

Decreased estrogen levels leads to pH

changes in vagina, favoring colonization of E.
coli, risk of UTI
Prostatic enlargement can lead to urinary
obstruction, increased residual urine &
infection

Palmer, 2004

Age-Related Changes in the

Urinary System
Structure

Change

Impact

Glomeruli

number
surface area

Tubules

thickened membrane
fatty degeneration
shortening

tubule

Renal
vasculature

stiffening
narrowing

Connective
tissue

expandability &
compressibility of
bladder

filtration of blood
glomerular filtration rate by 30-40%
transport
urine-concentrating capacity
Na conservation
renal acidification
blood flow
efficiency in removal of waste
product
bladder capacity
residual urine volume after voiding
Palmer, 2004

Urinary Tract Infection

Urinary

tract infectionmost common source of

bacteremia, a dangerous systemic infection in longterm care facilities

Bacteremia40

times more likely to occur in

catheterized than non-catheterized residents

Bacteremia

leads to significant morbidity and mortality

in the vulnerable elderly

Nicolle, 2005

Risk Factors of UTI

Lithiasis
UT obstruction
Polycistic kidney
Papillary necrosis
DM
Post transpalntation
Analgetic nephropathy
Sickle-cell disease
Coitus
Pregnancy and Contraception w/ progesteron
Cathetherization

Risk factors for UTI

pregnancy, spermicidal
contraceptives,
diaphragm, estrogen
deficiency, diabetes.

in females:

In males:

lack of circumcision, prostatic hypertrophy,

use of condom catheter.
in both :

old age , obstruction, vesicoureteric reflux,

instrumentation, neurogenic bladder, renal
transplantation.

Depending on the location of infecting bacteria,

distinct diseases will arise
Urethritis :
Painful urination and

burning
Cloudiness in urine
Blood in urine
Micro organism counts:
100,000/ml
(traditional)
1000/ml of one type
100/ml of E.coli

Cystitis :
Inflammation of the bladder,

but known to patients as

any UTI.
Infection caused by
bacterial infection mainly E.
coli.
Symptoms include painful,
burning, urgent urination
and WBC in urine.
Women mainly get this
because of the shorter
urethra, which puts it closer
to the anus where E.coli is
found.

Pyelonephritis
Acute infection of the

kidneys caused by
progressively untreated
cystitis
Symptoms include
fever, loin pain,
increase in WBC, and
bacteraemia
Can compromise kidney
function and require IV
antibiotics

Chronic

pyelonephriti :
Caused by chronic
inflammation of renal
and tubular tissue with
scarring and shrinkage
secondary interstitial
fibrosis.

Organisms associated with UTI

Gram negative organisms

Gram positive organisms

Escherichia coli > 80%

Klebsiella species
Proteus common in males
Enterobacter species < 2%
Pseudomonas species < 2%

Enterococci species
Staphylococcus

saprophyticus
Staph. aureus (uncommon)
Group B strep (uncommon)

Virulence
Infection is usually an interruptive

aberration of the balance

In order to exert damage, bacteria either
invade normally sterile compartments of
the body where they multiply, or they
produce toxins with general or highly
specific effects
UTIs may occur either because of the
pathogenicity of the organism, the
susceptibility of the host or a combination
of both factors

Virulence factors include:

Toxins
Factors for adherence on surfaces such

as epithelia
Degrading enzymes for maceration of
tissue
Factors promoting endocytosis or
preventing phagocytosis
Factors to overcome or survive
mechanisms of the host defense or
combinations of factors of the five groups

Confuse ... ?

Loking for more inspiration

Pathogenesis of UTI
Host defences:
Urinary bladder is usually resistant to

bacterial colonisation.
Bacteria accessing the bladder are
eliminated by:
- flushing
mechanism
- urine inhibitors (PH,
osmolality, urea)
- uroepithelial
defences (cytokines,PMNs)
- TammHorsfall protien

Pathogenesis of UTI
Organism features:
Most E.coli causing UTI belong to O,K

and H serotypes.
Uropathogenic E.coli virulence factors: Have fimbria (for adherence). - Secrete
hemolysin & aerobactin. - Resist serum
bacterical action.
- Have higher K
capsular antigen.
Adherence is important in other
bacteria.

Pathogenesis of UTI
Periurethral area & urethra are colonised

by bacteria.
Bacteria enter bladder in susceptable
host.
Adherence properties enable pathogens
to colonise bladder.
Pathogens attach to uroepithelial mucosa
secretion of cytokines recruitment
of PMNs inflammation.
Pathogens may ascend through ureter to
kidney pyelonephritis.

Clinical Manifestation
Asymptomatic bacteriuria
Acute cystitis
Acute pyelonephritis
Uncomplicated /
complicated UTI

Clinical Presentation of UTI

Asymptomatic bacteriuria:
Common in females & elderly.
25% develop symptomatic UTI .
25% clear spontaneously.
Spontaneous cure & reinfection are common.

Cystitis:
Frequency, dysurea , urgency.
Suprapubic discomfort +/- tenderness.
Fever is often absent.

Acute pyelonephritis:

Fever, abdominal pain, vomiting.

Dysuria ,frequency, flank or loin pain.
Flank or loin tenderness.
In elderly: symptoms are often

atypical.
Bacteremia is common.

Special situations

UTI in pregnancy (1)

Asymptomatic bacteriuria occurs in 4-

8%.
Of these: 25% develop acute
pyelonephritis.
Pyelonephritis in pregnancy predisposes
to:
- premature delivery.
- low birth weight
infant. - increased newborn mortality.

Catheter associated UTI (2)

Bacteriuria occurs in 10-15% of cathed

pts.
All chronicly cathed pts. develop
bacteriuria.
Organisms: E.coli, Proteus, Klebsiella, Serratia
Pseudomonas, Enterococci,
Candida.

Antibiotic resistance is common.

Symptoms are often absent or minimal.
Intermittent cathing reduces infections.

Diagnosis of UTI

History & Physical Examination

Age-related Risk Factors for UTI
Advanced Age
Fecal incontinence/impaction
Incomplete bladder emptying or neurogenic bladder
Vaginal atrophy/estrogen deficiency
Pelvic prolapse/cystocele
Insufficient fluid intake/dehydration
Indwelling foley catheter or urinary catheterization

or instrumentation procedures

Age-related Risk Factors for UTI

Diabetes or immunosuppression
Benign prostatic hypertrophy
Bladder or prostate cancer
Urinary tract obstruction
Spinal cord injury
Mahan-Buttaro, Aznavorian & Dick, 2006

Urine dipstick:

- leukocyte esterase
- nitrite
Urine microscopy:

-WBCs, WBC casts, RBCs

- Bacteria ( 1 bact/hpf =
significant )

Complicated vs Uncomplicated
UTI
UTIs in elderly men are always considered

complicated
UTIs in women are complicated when:
Hx of recurrent UTI
Secondary to structural abnormalities
Catheters
Stones
Urinary retention
Abscess formation or urosepsis

Primary diagnostic and treatment focus in

research studies have been related to the

elderly female population

Swart, Soler & Holman, 2004

Complicated vs Uncomplicated UTI

Recurrent UTIsculture-confirmed UTIs
* >3 in 1 year or
* > 2 in 6 months
Relapse UTI

occurs within 2 weeks of Rx

of an earlier UTI
same pathogen
Re-infection UTI occurs >4 weeks after
earlier UTI
different pathogen
Swart, Soler & Holman, 2004

Causative Pathogens
UTI in Women
Escherichia coligram (-) etiologic agent in ~
=
80% of all UTIs
Research indicates primary source of
microbial invasion is retrograde colonization
by intestinal pathogens
Other factors influencing colonization: vaginal
pH, urethral length, capacity of bacteria to
adhere to urothelium
Osborne, 2004

Polymicromial bacteriuria
Contamination most frequent cause of

multiple microorganisms
25-33% in LTCFs may be polymicrobic due to
fistulas, urinary retention, infected stones, or
catheters
Midthun, 2004

Age/Type Specific Pathogens

Younger patients, rare in elderlyStaphylcoccus,

saprophyticus (gram pos.) 10-15%

Elderly diabetics

Klebsiella species (gram neg.) most common

LTCF elderly
E. coli ~ 30%
Proteus species (part of host flori in GI tract) ~ 30%
Staphylcoccus aureus, Klebsiella, Pseudomonas (gram

neg.) and Enterococcus (gram pos.) ~ 40%

Swart, Soler & Holman, 2004

Symptoms vs Asymptomatic
Bacteriuria
Asymptomatic Bacteriuria (ASB)
Defined as the presence of bacteria in urine of patients
who do not have dysuria, urinary frequency, urgency,
fever, flank pain, or other symptoms related to irritation of
the urethra, bladder, or kidney

Swart, Soler & Holman, 2004

Strictly definedexists when 2 urine cultures done with

clean-catch specimens are positive in a patient who has no

urinary tract symptoms

Frequent in elderly, even > prevalent in residents of LTCF:

elderly >70 yrs old

women: 16-18%
men: 6%

Foxman, 2003

Symptomatic vs. Asymptomatic

Bacteriuria, contd
Asymptomatic Bacteriuria (ASB)
Most ASB in the elderly is associated with complicating

factors such as:

Hormonal:
Anatomical:
Functional:
Metabolic:

post-menopausal women
prostatic obstruction in men, cystocele in women
CNS, i.e., P.D. & dementia
diabetics (ASB females with Type 2 diabetes

29%)
Immunological: s in inflammatory mediators (cytokines, acute
phase proteins)
Instrumental:
indwelling catheteralways bacteriuric symptoms
Wagenlehner, Naber & Weidner, 2005

Pyuria

Diagnostic Criteria

A host response to infecting bacteria causing an increase

of white blood cells or pus in the urine

Associated with presence of both symptomatic and
asymptomatic UTIs in elderly
Level of pyuria is when infected with a gram negative
organism
Most research finds this is so common that it has
questionable value in UTI detection and as an indicator
for Rx in the absence of clinical symptoms
McGeer et al. (one of the most commonly used consensus criteria

in LTCF for UTI detection in Canada) rejects it as being a reliable

predictor of bacteriuria or symptomatic infection
Midthun, 2004
Juthani-Mehta,, 2005

Screening/Diagnosis
Infectious Disease Society of America:
Guidelines for Dx & Rx of ASB in adults
1.

ASB Dx based on results of a culture from cleancatch specimen (* important to minimize

contamination)

Women: bacteriuria = 2 consecutive voided urine samples

w/isolation of same strain in cfu/mL >100,000
Men:
bacteria = single, clean-catch specimen with 1
bacterial species isolated in > 100,000 cfu/mL
Both:
single catheterized urine specimen with 1
bacterial
species isolated in a count of > 1,000 cfu/mL

Screening/Diagnosis
Guidelines, continued
2. Pyuria accompanying ASB not an indication for

antimicrobial Rx (A-2)
3. Pregnant women should be screened in early
pregnancy, at least once & treated if positive (A1)
4. Screening of ASB & Rx if positive before these
urological procedures:

Transurethral resection of prostate (A3)

Procedures anticipated to cause possible mucosal
bleeding (A-3)

Screening/Diagnosis
Guidelines, continued
5.

No screening for ASB: (A-1 & A-2 strongly

recommended via research evidence)

6.
7.

Pre-menopausal, non-pregnant women (A-1)

Diabetic women (A-1)
Community older adults (A-2)
Institutionalized elderly (A-1)
Spinal cord injury (A-2)
Indwelling-catheterized patients (A-1)

Antimicrobial Rx of asymptomatic women with

catheter-acquired bacteriuria persisting 48 hrs after
removed, should be considered (B-1/good)
No screening or Rx of ASB renal transplant or solid
organ transplant recipients (C-3/weak)
Infectious Disease Society of America, 2005
Nicolle et al. 2005
www.guideline.gov/summary/summary

Laboratory Analysis, continued

Routine UrinalysisKey Indicators of Infection

Urine collection

1st morning specimen is best

Straight catherization for those incontinent, functionally or cognitively impaired

Specific gravity

Measure of kidneys abiltiy to concentrte urine

Range of SG depends on state of hydration

Appearance

Cloudy, may not indicate WBCs

Could indicate a change in urine pH causes precipitation
Alkaline urine phosphates cloudy
Acid urine urates cloudy

Color

Pale yellow to amber

Variations can be caused by medications, disease processes (*nl urine darkens
on standing 30 min. after voidingoxidation of urobilinogen to urobilin)

Odor

nl faint odor when freshly voided

Foul-smellingoften presence of bacteria which splits urea to form ammonia
Fischbach, 2004

Laboratory Analysis, continued

Routine Urinalysis, continued
pH

Acid or basemeasures free H+ ion concentration in urine 7.0neutral.

Indicates kidney function
Determines if systemic acid-base disorders of metabolic/resp. origin
control of pH manages bacteriuria, renal calculi & drug Rx
bacteria from a UTI produce alkaline urine

Blood or
Hemoglobin

Always an indicator of kidney/UT damage

Protein (Albumin)

Single most important indication of renal disease

Microalbuminuria

Below dipstick range of detection

Detects deteriorating renal function in diabetic patients (standard screener)

Fischbach, 2004

Laboratory Analysis, continued

Routine Urinalysis, continued
*Nitrite (Bacteria)

Dipstick - rapid, indirect method to detect bacteria

common gram-negative organisms contain enzymes reduce nitrate
in urine to nitrite
some UTIs are caused by organisms that do not convert nitrate to nitrite
(e.g., staphylococcus, streptococci)

*Leukocyte

Esterase is released by leukocytes (WBCs) in urine

Microscopic exam & chemical test

Esterase

__________
*U/A testing positive for nitrite & leukocyte esterase should be cultured for bacterial pathogen
Fischbach, 2004

Other Laboratory Tests

Complete Blood Count with Differential
Indicated to R/O bacterial infection supports

treatment plan
Careful evaluation of WBC & differential (left shift)

Electrolytes
R/O dehydration & if IV fluids replacement needed

BUN, Creatinine
Determine renal function for nephrotoxic

medications

Blood Culture
Identify bacteremic organism in suspected

urosepsis

Urine Culture and Sensitivity

Traditional gold standard for significant

bacteriuria >100,000 cfu/mL of urine. Some

argue criteria for bacteriuria is only 100
cfu/mL of a uropathogen in symptomatic
females or 1,000 in symptomatic males.

Bacterial identification from urine C&S, key

in males and females with complicated

UTIs.

Urine culture:

Significant bacteriuria= 100K cfu/ml

symptoms: 1 +ve cuture = infection
Symptoms: 10K cfu/ml = propable

infection
Asymptomatic: 2 +ve cultures =
infection
False negative : antibiotics, antiseptics,
urethral

syndrome,TB kidney, diuresis.

Treatment of UTI

Treatment Plan
Early detection/Rx goal is to prevent systemic

infection, bacteremia
Initiation of antibiotic treatment is recommended for a
clinically-diagnosed UTI. Adjust medication when urine
C&S is final
Selection of antibiotic must be individualized and
consider:
Side effect profile
Cost
Bacterial resistance
Likelihood of compliance (convenience, fewer pills/day s

compliance)
Effect of impaired renal function on dosing
Possible adverse drug reactions in elderly (multiple drugs, comorbidities.
Osborne, 2004
Swart et al. 2004

Treatment Plan
AB Rx for at least 10 days for institutionalized

elderly, as short-term therapy may not be as

effective.
Ten-14 days, if indicated, for complicated UTI.

(recommended for males)

Evercare, 2004

Conventional regimen of 7-10 days duration is

usually recommended.
Wagenlehner et al. 2005

Asymptomatic bacteriuria

No urgency to treat confirm by 2

cultures.
Treatment is indicated in :
- Children with VU reflux
obstruction

- Pregnancy
- Urinary

Treatment is not indicated in : - Young

nonpregnant women without
structural abnormalities - Elderly patients

Cystitis
young females: 3 days of oral therapy
(fluoroquinolone,cotrimoxazole,cefuroxime,augmenti
n)

In females: symptoms x 7 days or

history of
previous
infection 7 days therapy.
In males : oral therapy for 7-10 days.

Acute pyelonephritis
Mild infections are treated orally.

(fluoroquinolones,co-trimoxazole,cefuroxime)

Moderate - severe infections parenteral trt.

(aminoglycosides,ceftriaxone,aztreonam,tazocin)

Therapymarked decline in bact.count after

48hrs.
Persistant fever, +ve blood culture after 3
days of therapy..R/O obstruction, abscess.
After defervescence..change to oral therapy
to complete 2 weeks.
In males look for a predisposing cause.
FU urine cultures 2 weeks after end of
therapy.

Treatment Plan
Complicated UTI
Can be common in LTC patients
Associated with azotemia, obstruction, or indwelling foley
Can lead to bacteremia, life-threatening systemic infection

Recommended Treatment for Acute Complicated UTI

IV antibiotic therapy--*consider renal & hepatic
elimination, creatinine clearance for dosage
adjustment
3rd generation cephalosporin (Ceftriaxone = Rocephin) Rx

1 gram IV every 24 hours

Or if fluoroquinolones (Levofloxacin = Levaquin) 250-500
mg IV every 24 hours
Continue until afebrile, minimum of 48 hrs, then start oral
therapy and fluids x 14 days.
Mahan-Buttaro et al., 2006

Relapse of infection:
Relapse may be due to :
- renal invovement
- structural abnormalities
- chronic bacterial prostatitis

Relapses need to be treated for 2 weeks.

Obstuction should be corrected .
If uncorrectable obstruction: treatment is

prolonged for 4-6 weeks or as required.

The latter group needs FU by monthly
cultures and annual assessment of kidneys.
In males R/O chronic prostatitis.

Recurrent UTI
Infrequent symptomatic UTI : treat attacks.
In females, reinfections may be related to

sexual activity attacks may be reduced by:

- avioding use of spermicidal contraceptives voiding after intercourse

- post coital single dose
therapy

If no precipitating factors long term

prophylaxis.
Long term prophylaxis is also indicated for
frequent asymptomatic infection in:
Children with VU reflux
- Patients with obtructive uropathy

E-coli Resistance
E coli often carry multi drug resistant

plasmids and under stress also can transfer

these plasmids to other species.
Marked increase in E coli resistance is
occurring over the last decade to various
antibiotics including pencillins,
cephalosporins, Trimethoprim sulfamethoxazole etc.
Treatment usually is based on local
resistance rates / patterns.

Prevention & Treatment Plan

Recommendations/Considerations/Prevention

Indwelling-Catheterization
Foley catheterization should be avoided if at all possible
Most effective means of UTI prevention is limitation of

chronic indwelling catheters.

Wagenlehner et al. 2005

So I learned something ,how

about you ?