Objectives

Distinguish types of UTI, including bacteriuria, urethritis,

cystitis, and pyelonephritis
Describe the pathophysiology related to UTI, such as
organisms and host factors
Describe typical clinical presentations, and elicit a pertinent
history, in a patient with UTI
Describe the diagnostic methods and diagnostic criteria for
the various types of UTI
Describe modes of therapy for acute, chronic, and
complicated UTI, including prophylaxis for recurrent
infection

Introduction
UTIs: presence of micro organisms within the urinary tract
May be difficult to distinguish between contamination,
colonisation or infection
UTI can occur from infancy through old age, Incidence is
highest in sexually active adolescent females.
Rare in men and in children, common in females, 10 - 20% of
all females will experience a UTI during their lifetime
1%-6% of general practitioner visits are for UTIs,
If left untreated, simple cystitis may progress to renal scarring
ie/pyelonephritis which may develop renal insufficiency

Terminology
Asymptomatic
Bacteriuria

UTI

Cystitis

Asymptomatic
UTI

Symptomatic
UTI
Pylonephritis

Urosepsis

Pyuria

Definition of UTI

Bacteriuria greater than >105 bacteria/ml**

Pathogenic microorganisms in urine, urethra, bladder, kidney, prostate

From midstream clean catch urine sample
If from catheter specimen can be significant with 10 2 or 104 organisms/mL
** Up to 50% of women with symptomatic infections have lower counts.
** < 1% of the represent contaminants; at counts of 10 3 104 there is a 50% chance
the results represent contamination.
Second criteria: presence of pyuria (> 5 WBC/HPF) on the urinalysis
Presence of pyuria correlates poorly with diagnosis of UTI

Cystitis
Infection of the urinary tract limited to the bladder, usually involving
only the mucosal surface

Most common type of UTI

- painful/burning urination
- urgency or frequency
- absence of symptoms or physical signs suggesting
inflammation at other sites within the urinary tract
clinical criteria are notoriously inaccurate in identifying the actual
anatomic site of infection

Pyelonephritis
Infection of the kidney
clinical diagnosis which implies a more invasive
infection
inflammation of the kidney and renal pelvis is
assumed to be present when patients have pain or
tenderness involving the flank, together with other
clinical or laboratory evidence of UTI
-fever, nausea, chills, malaise, headache, etc

Asymptomatic Bacteriuria
The presence of bacteria in the urine of a person without symptoms of
infection.

Should not be called a UTI

Should not be treated with antibiotics
Clinical significance controversial outside certain patient populations
- pregnant women
- patients undergoing invasive procedures of the UT

the presence of bacteria in urine does not necessarily imply infection

 Complicated infections

- underlying abnormality that predisposes patient to UTI

or makes UTI more difficult to treat effectively
Recurrent Infections
Relapse - recurrence of infection by same organism

after discontinuation of treatment

Reinfection - recurrence of infection by a different
organism after discontinuation of treatment

UTI Classification
Lower Tract

Upper Tract

Superficial or mucosal

Invasive

Urethritis

Pyelonephritis

- Urethra
Cystitis
- Bladder
prostatitis

- Acute or chronic
- intrarenal and
perinephric abscess

UTI Classification
Uncomplicated

Complicated

Not due to functional or

structural abnormality

Due to predisposing
lesion

Short course of therapy

Longer course of therapy

No sequelae

Leads to bacteremia and

recurrences

Also categorized into

Non-catheter associated
(community acquired)
Catheter associated
(hospital acquired)

Predisposing conditions to UTI

Gender (females>males)
Age
Pregnancy and menopause
Use of diaphragm

Congenital
abnormalities
Stone (kidney or any
part of tract)

Sexual intercourse

Urinary catheters

Vesicoureteral reflux

Diabetes mellitus
Inadequate fluid intake

Causative Organisms
Majority of UTI are due to a single pathogen
(commonly bacterial; virus rare)
>> by aerobic gram negative rod of the GIT.
~ 85% of all UTI : E. coli
~10% : Klebsiella, Proteus, Pseudomonas,
Enterobacter
~ < 5%: Staph aureus, enterococcus, chlamydia,
fungus, TB, other.

Causative Organisms
Community-acquired

Hospital-acquired

Escherichia coli*

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeroginosa

Proteus mirabilis

Proteus sp.

Staphylococcus
saprophyticus
Enterococcus faecalis

Enterobacter sp.
Serratia sp.
Enterococcus sp.

Uro-pathogens
E.coli, Klebsiella spp.
-intrinsic gut organisms
-highly motile
-produce fimbriae (pili) attachment
Proteus, Morganella, Providencia
-Urease producing organisms
-increases urinary pH - leads to crystal formation

Community-Acquired UTI
E.coli

S.epi &
gm - enterics
Enterococcus
K.pneumoniae

Proteus
S.saprophyticus

Nosocomial UTI
catheter associated
Short Term

Long Term
E.coli

Enterobacter

E.coli

Proteus

Enterococcus

Candida

Proteus

Providencia

S.aureus
Pseudomonas

Morganella
Pseudomonas

Bacterial factors: E. coli

> 700 serotypes based on O (somatic/surface cell
wall), H (flagellar), and K (capsular) antigens.
Serotyping is still important in distinguishing the small
number of strains that actually cause disease.
E. coli 3 types of infections in humans: UTI, neonatal
meningitis, and gastroenteritis depend on virulence
determinants.

Bacterial factors: E. coli

Adherence
Adhesins
Fimbriae
Non-fimbrial Adhesins
Biofilms
Important in catheter UTI
protects bacteria from host defenses & antibiotics
Soluble Virulence Factor Production
Disrupt bladder protective mucus layer

Bacterial factors: E. coli

Iron Acquisition Mechanisms
Siderophores and Haemolysins
Growth

Serogroup and Serum R

O ag LPS outer G -ve
Prevent complement destruction

Capsules
K ag covers bacteria capsule
Protects phagocytosis and complement attack

Bacterial factors: E. coli

Ig Proteases
Cleave gut IgA

Ureteric Paralysis
P. Fimbriae and endotoxin

Motility
Ascent of LUT

Urease Production
Hydrolyse urea and increases ammonia
which increases bacterial adherence

Summary of the Virulence Determinants of Pathogenic E. coli

Adhesins

- CFAI/CFAII
- Type 1 fimbriae
- P fimbriae
- S fimbriae
- Intimin (non-fimbrial adhesin)

Invasins

- Hemolysin
- Siderophores & siderophore uptake
systems
- Shigella-like "invasins" for intracellular

Antiphagocytic surface properties

- capsules
- K antigens
- LPS

Defense against serum bactericidal reactions

- LPS
- K antigens

Defense against immune responses

invasion & spread

- capsules
- K antigens
- LPS
- antigenic variation

Motility/chemotaxis

Genetic attributes

- Flagella

Toxins

- LT toxin
- ST toxin
- Shiga-like toxin
- Cytotoxins
- Endotoxin (LPS)

- genetic exchange by transduction &

conjugation
- transmissible plasmids
- R factors & drug resistance plasmids
- toxin & other virulence plasmids

Pathogenesis
- Ascending route of infection
Most common route in females (95%)
- Retrograde via the urethra
- Hematogenous route
- Rare (<3%)
- endocarditis, bacteremias, disseminated
infections
Complicating factors such as catheters, nephrostomy
tubes, surgery, urinary stones, etc

Host Defense Mechanism

Normal anatomy = physical barriers: urethral length, urethral
valves, antegrade flow
Lactobacilli Low urine pH, produce hydrogen peroxide
High urea and organic acid concentration
Prostate gland: secretes infection-fighting substances
Micturition (urination) flushing
Antiadherence
- Urinary mucus: coats bladder epithelial cells
- Tamm-Horsfall protein: glycoprotein that prevents
organisms from binding to mucosa

Clinical Presentation
Suprapubic pain, pain or burning during urination
frequency and urgency of urination
Dysuria
Nocturia
Hematuria
Cloudy urine
Foul or strong urine odor
Upper: fever, chills, malaise, N/V, weight loss, flank or
back pain

DIAGNOSTIC EVALUATION

Diagnosis of UTI
History
Physical exam (PE)
Lab
Urinalysis
Urine culture
Sensitivity

Imaging study

Diagnosis of UTI
Determination of the number and type of bacteria important
diagnostic procedure.
Symptomatic
105 CFU bacteria/ml
Asymptomatic
105 CFU bacteria/ml on 2 consecutive specimens
Catheterized patients
102 CFU bacteria/ml

antibiotic, high urea concentration, high osmolarity, low pH

inhibits bacterial multiplication low bacterial colony counts

Diagnosis of UTI
Rapid methods: detect bacterial growth by photometry,
bioluminescence rapid results, usually in 1 to 2 h.
Microscopic bacteriuria, is found in > 90% of specimens from patients
whose infections colony counts of at least 10 5/mL, (very specific).
Infections with lower colony counts (102 to 104/mL) bacteria ve.
Bacteria +ve infection, bacteria ve not exclude the diagnosis.
Pyuria is a highly sensitive indicator of UTI in symptomatic patients.
The leukocyte esterase "dipstick" method is less sensitive
Sterile pyuria unusual bacterial agents (C. trachomatis, U.
urealyticum, and M. tb or with fungi) or noninfectious urologic conditions
(calculi, anatomic abnormality, nephrocalcinosis, vesicoureteral reflux,
interstitial nephritis, or polycystic disease).

History and Physical Examination

Costovertebral angle (CVA) tenderness
Abdominal tenderness or mass
Palpable bladder
Dribbling, poor stream, or straining to void
Examine the pelvic & vaginal area in women for signs of
irritation, vaginitis, trauma, or sexual abuse.
Men require a digital rectal examination to determine if
prostate enlargement is present

Specimen collection
Clean catch mid stream specimens

- most frequently used method

- urethra cleaned prior to collection
- first void urine allowed to pass to clear urethra
- mid-stream collected in sterile container
Suprapubic aspiration / straight catheters
- invasive
- specimen obtained directly from bladder
Indwelling catheters
- urine obtained by inserting needle into catheter
- preferable from new catheter, rather than old catheter

Specimen transport
Sent to and processed by lab as quickly as possible
- Require: method of collection
time of collection
patients antibiotics
Specimens not received by lab in 1-2 hours MUST be
refrigerated
Urines not received within 24 hours or not refrigerated will be
rejected by laboratory

Urinalysis
Offers a number of valuable clues for an accurate diagnosis:
- Color and cloudiness of urine
- Acidity
- White blood cells (leukocytes).
Treatment can be started without the need for further tests if
the following urinalysis results are present in patients with
symptoms and signs of UTIs:
- A high white cell count
- Cloudy urine

Urinalysis
Parameter

Normal values

UTI

Appearance

Yellow

Cloudy

pH

4.5-8.5

Alkaline

Protein

Negative

Positive

Nitrite test

Negative

Positive

RBC

Negative

Positive

WBC

0-5 / hpf

> 5 / hpf

Cast

Negative

Positive

Absent

Many present

Bacteria

Urine culture
Results are best interpreted with knowledge of the collection
method and results of the urinalysis.
A clean-catch urine sample with > 105 CFU of a single organism
is classic criteria for UTI.
102 to 104 accepted as significant if patient symptomatic
Contamination with perineal flora may mask an existing UTI.
UT abnormalities may be associated with multiple organisms.
Cultures with growth of more than 10,000 CFU from bladder
catheterization or suprapubic aspiration should be considered
significant for UTI with any colony count.

Imaging Techniques
Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If suspects obstruction or an abscess
VUR ultrasound and voiding cystourethrogram

TREATMENT

General Principles of treatment

1. Except in acute uncomplicated cystitis in women, a urine culture, a
Gram stain, or an alternative rapid diagnostic test should be
performed to confirm infection before treatment is begun.
2. Factors predisposing should be identified and corrected.
3. Relief of clinical symptoms bacteriologic cure.
4. Each course of treatment failure or cure.
5. In general, lower tract short courses, upper tract longer.
6. community-acquired infections antibiotic-sensitive strains.
7. In patients with repeated infections, instrumentation, or recent
hospitalization antibiotic-resistant strains should be suspected.

Goals of Therapy
Prevent or treat systemic consequences
Relieve symptoms
Eradicate invading organism
Eliminate uropathogenic bacterial strains from fecal
& vaginal reservoirs
Prevent reoccurrence of infection
Prevent long-term sequelae

Antimicrobial Selection
Empiric Therapy
- based on most probable pathogens
- local rates of resistance
- acute infection vs chronic
- reinfection or relapse
- indwelling catheter etc
Good urine concentration
Minimal effects on fecal and vaginal flora
Acceptable safety profile
Cost-effective

Bacteria by Site of Infection

Mouth

Skin/Soft Tissue

Bone and Joint

Peptococcus
Peptostreptococcus
Actinomyces

S. aureus
S. pyogenes
S. epidermidis
Pasteurella

S. aureus
S. epidermidis
Streptococci
N. gonorrhoeae
Gram-negative rods

Abdomen

Urinary Tract

Upper Respiratory

E. coli, Proteus
Klebsiella
Enterococcus
Bacteroides sp.

E. coli, Proteus
Klebsiella
Enterococcus
Staph saprophyticus

S. pneumoniae
H. influenzae
M. catarrhalis
S. pyogenes

Lower Respiratory
Community

Lower Respiratory
Hospital

Meningitis

S. pneumoniae
H. influenzae
K. pneumoniae
Legionella pneumophila
Mycoplasma, Chlamydia

K. pneumoniae
P. aeruginosa
Enterobacter sp.
Serratia sp.
S. aureus

S. pneumoniae
N. meningitidis
H. influenza
Group B Strep
E. coli
Listeria

Antimicrobial Therapy
Cystitis - usually responds to 3 days of treatment
- effective concentrations into the urine > serum
uncomplicated pyelonephritis - 2 weeks treatment
- effective concentrations into the urine = serum
complicated infections / prostatitis - 6 weeks
IV antibiotics may be required in seriously ill patients,
but oral drugs usually effective

Antimicrobial Therapy
Acute Uncomplicated cystitis
Trimethoprim/sulfamethoxazole (TMP/SMX)
1 DS (160/800 mg) BID x 3 days
Fluoroquinolones:
Ciprofloxacin 250 mg BID x 3 days
Levofloxacin 250mg QD x 3 days
Gatifloxacin 200 mg QD x 3 days
Nitrofurantoin: 100 mg QD x 3 days
Cephalosporins, doxycycline, amoxicillin/clavulanate

Antimicrobial Therapy
Acute pyelonephritis
Duration on therapy= 7-14 days
TMP/SMX
1 DS (160/800 mg) BID x 14 days
Fluoroquinolone
Ciprofloxacin 500 mg BID x 14 days
Levofloxacin 250mg QD x 14 days
Gatifloxacin 250 mg QDx 14 days
Cephalosporins, doxycycline, amoxicillin/clavulanate
For more seriously ill patients IV therapy

Specific
Recommendations

Acute uncomplicated cystitis

in young women
Objective:
- eradication of superficial mucosal infection
- eradication of uropathogenic clones
Short course therapy:
- single-dose and 3-day course
- equally efficacious, but re-infection more common with
single-dose therapy
TMP/SMX or fluoroquinolones

Contraindications of
short-course therapy
Any man with UTI
Anyone with overt PN
Patients with symptoms of > 7 days duration
Patients with underlying structural of functional defects of
the urinary system
Immunosuppressed individuals
Patients with indwelling catheters
Patients with a high probability of infection with antibioticresistant organisms

Women who present with complaints

of dysuria and frequency
Treat with short-Course Therapy
Follow-up 4-7 days later

Asymptomatic

Symptomatic

No Further
Intervention

Urinalysis, Urine culture

Both
Negative
Observe,
Treat with
Urinary analgesia

Pyuria,
No Bacteriuria
Treat for
Chlamydia
trachomatis

Fig. Clinical approach to the women with dysuria and frequency

Bacteriuria
w./w.o Pyuria
Treat with
Extended
Course

Recurrent UTI in Young Women

Approximately in 20% cases
Simple interventions approach
Preventive strategies effective at low doses, minimal side effects,
minimal impact on the make-up & antibiotic susceptibility of the bowel
flora
Acidify the urine methenamine + ascorbic acid
Nitrofurantoin 50 mg or macrocrystals 100 mg at bedtime
Low dose TMP/SMX half a tablet, 3 times weekly at bedtime.
Duration of treatment
Relapse or repeated:
- relapse: fails short-course intensive course of prolonged therapy.
- repeated: respond to short-course long-term prophylaxis

History of Multiple UTI

New Acute Symptomatic UTI
Treat with Short-course Therapy
Follow-up 4-7 Days later
Success of Treatment

Failure of Treatment

Patient has
Recurrent Reinfection

Antibiotic-Resistant
Infection

Candidate for
Long-Term
Low-Dose
Prophylaxis

Treat with
Short-Course
Regimen to Which
Organism
Susceptible

Success

Antibiotic-Susceptible
Infection
6 weeks of
High-Dose
Curative
Therapy
Failure

Fig. Clinical approach to the women with recurrent UTI

Acute Uncomplicated Cystitis

in Older Women

Frequency higher than in younger age groups:

- Residual urine consequence of childbirth & loss of pelvic tone
- Lack of estrogens change in the susceptibility of the uroepithelium &
vagina to pathogens
- changes in the vaginal microflora as the loss of lactobacilli

Symptomatic with pyuria & negative cultures:

- genitourinary tuberculosis
- Systemic fungal infection
- diverticulitis on the bladder or ureters

Estrogen replacement therapy (local or oral) restores the atrophic

genitourinary tract re-appearence of lactobacilli vaginal pH &
vaginal colonization by Enterobacteriaceae

UTI in Pregnancy
should be screened for UTIs high risk for UTIs and their
complications.
Asymptomatic bacteriuria have a 30% risk for acute PN
short course of antibiotics (3 to 5 days).
Uncomplicated UTI need longer-term antibiotics (7 to 10
days).
Sulfonamides, nitrofurantoin, ampicillin, cephalexin safe
in early pregnancy
Avoid: sulfonamides (near term kern icterus ), TMP (toxic
effects in the fetus at high doses), fluoroquinolone (fetal
cartilage development),

UTI in Men

Uncommon in younger than 50 years

Older than 50 years assumed from prostate or kidney

Recurrent infection sustained focus within the prostate

Difficulty of eradication of prostatic foci

- failure antimicrobial diffuse into the prostatic gland
- prostate may harbor calculi block drainage or act as a foreign bodies
- enlarged & inflamed bladder outlet obstruction

Intensive therapy: at least 4-6 weeks with TMP/SMX, fluoroquinolones

Failure treatment:
- Anatomic factors
- Infection due to E. faecalis or P. aeruginosa

Treatment relapse Long term antimicrobial suppression, repeated

treatment courses for each relapse and surgical removal of infected prostate
gland

Management of
Catheter-Induced UTI

Preventing Catheter-Induced Infections

Catheter-induced UTIs are very common and preventive measures are
extremely important.
Catheter Coatings.

Catheter coatings, such as silver nitrate, antibiotics, and other substances,

are being tested and are showing some benefits, but the problem is still not
resolved.

One promising catheter (LoFric) uses a so-called hydrophilic coating

consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the
catheter surface, putting up a water barrier to reduce friction. In a 2003
study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters.

If a catheter is required for long periods, it is best to use it intermittently if

possible (as opposed to an indwelling catheter).

replacing it every 2 weeks to reduce the risk of infection and irrigating

the bladder with antibiotics between replacements.

Preventing Catheter-Induced Infections

Daily Hygiene. Tips to prevent infection:
Drink plenty of fluids, including 3 glasses of cranberry juice a day
The catheter tube should be free of any knots or kinks
Clean the catheter and the area around the urethra with soap
and water daily and after each bowel movement. (Women should
be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area
Keep the drainage bag off the floor
Stabilize the bag against the leg using tape or some other
system

Antibiotics for Catheter-Induced

Infections
UTIs with symptoms treated and removed the catheter. , if possible.
A major problem in treating catheter-related UTIs is that the organisms
involved are constantly changing.
Because there are likely to be multiple species of bacteria broad
spectrum antibiotic (fluoroquinolone group and drug combinations such
as ampicillin plus gentamicin or imipenem plus cilastatin).
Antibiotics to prevent a UTI is rarely recommended, despite bacteriuria.
Many catheterized patients do not develop symptomatic urinary tract
infections even with high bacteria counts.
If bacteriuria occurs without symptoms, antibiotic therapy has little benefit
if the catheter is to remain in place for a long period.

Prevention
Adequate fluid intake (6-8 glasses/day)
Appropriate hygiene and cleanliness of the genital
Pre & post-coital urination
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing
both at least once a day.
Take showers rather than baths.
Avoid douching or similar feminine hygiene products.
Urinate frequently.

Prognosis

Urinary discomfort and emotional distress. Impairment of a woman's QoL

during symptom periods social function, vitality, & emotional well being

Uncomplicated cystitis or PN complete resolution of symptoms.

Repeated episodes of cystitis nearly always reinfections, not relapses.

Acute uncomplicated PN rarely progresses to renal functional

impairment & CRD.

Repeated UTI relapse rather than reinfection search for an

underlying

Repeated symptomatic UTIs with obstructive uropathy, neurogenic

bladder, structural renal disease, or diabetes progress to CRD with
unusual frequency.

Asymptomatic bacteriuria in these groups as well as in adults without

urologic disease or obstruction predisposes to numbers of episodes of
symptomatic infection but does not result in renal impairment in most
instances.