Urinary Tract Infections

Overview of UTI

UTIs: presence of micro organisms within the urinary tract

May be difficult to distinguish between contamination,

colonisation or infection !!

Rare in men and in children, common in females

About 2/3rds of patients are women; 40% to 50% of women

have UTI at some point during their lives

Important complications of pregnancy, diabetes mellitus,

polycystic disease, renal transplantation, conditions that
impede urine flow (structural and neurologic)

If left untreated, simple cystitis may progress to renal

scarring ie/pyelonephritis which may develop renal failure

UTI by age and sex

Classification
Based

on anatomy

Upper UTI (pyelonephritis)

Lower UTI ( cystitis, urethritis)
Based

on clinical symptoms

Asymptomatic UTI
Symptomatic UTI
Based

on complication

Uncomplicated UTI: infection involving a structurally and functionally

normal urinary tract.
Complicated UTI : UTI with any underlying neurologic,structural or
medical problems (include UTI in male)

Definition or Terms
Urinary

Tract Infection :
A microbial colonization of the urine and infection of the
structure of urinary tract.
Bacteriuria : the presence of the bacteria in the urine
Significant bacteriuria 100.000 cfu/ml
Frequent recurrent > 4 events every year
Relaps

same organism, after eradication

Re-infection different organism, after eradication
Persistent

is the continued infection of the same

microorganism despite therapy

Definition or Terms
Upper

UTI: infection above the level of the bladder

Lower UTI: infection at or below the level of the
bladder
Urethral syndrome: clinical manifestations of lower
UTI (dysuria, frequency, urgency) without significant
bacteriuria
Pyuria: the presence of leukocytes]in urine, which
may or may not be caused by UTI.

Frequency of significant bacteriuria

After

one bladder catheterization: 2%

Medical outpatients: 5%
Pregnancy at term: 10%
Hypertensive patients: 14%
Diabetes mellitus: 20%
Women with cystocoele: 23%

Frequency of significant bacteriuria (2)

Congenital

urologic disease: 57%

Hydronephrosis;

nephrolithiasis: 85%

Indwelling

catheter, open drainage >

48 hours: 98%

Jackson et al, Arch Intern Med 1962; 110: 663)

Etiology of UTI

community-acquired UTI
Aerobic

gram-negative rods most often

E. coli accounts for about 90%
Staphylococcus saprophyticus has
been increasingly appreciated in recent
years
Rare: anaerobes; pyogenic cocci;
viruses

nosocomial UTI
E.

coli is the most common pathogen

However, also common are other
Enterobacteriacae (Proteus, Klebsiella,
Enterobacter, Serratia, Providencia species)
and Pseudomonadaceae (notably,
Pseudomonas aeruginosa)
Enterococci: often in obstructive uropathy
Yeasts: Candida albicans, others

Urease-producing
microorganisms
Urease

splits urea into ammonia, which has a

direct toxic effect on the kidney; inactivates
C4, and alkalinizes the urine with production
of struvite crystals (MgNH4P04.6H20) crystals

Proteus

mirabilis most often; also

Providencia, Morganella, S. saprophyticus,
Klebsiella, Corynebacterium D2; mycoplasma

UTI in children
Newborns:

overall rate is about 1%

(higher in males than in females)
Preschool children: UTI is 10 to 20
times more common in girls
School-aged children: about 1.2% of
schoolgirls have bacteriuria on any
given day

UTI in adults
Women:

bacteriuria increases with

age and sexual activity

Men:

bacteriuria is rare before age

50. Subsequently, bacteriuria
increases with onset of prostatism

Role of bacterial virulence in UTI

Bacterial

adherence to uroepithelial cells involves

specific binding of bacterial surface receptors
(adhesins) to complementary components on the
epithelial cells (receptors).

The

ability of E. coli to adhere to uroepithelial cells is

associated with the presence of pili or fimbriae.

Virulence

of E. coli strains multiple factors,

including adhesins, hemolysin, capsular
polysaccharide, aerobactin).

Host defenses

Antibacterial properties of urine

Osmolality

(extremes of high or low

osmolalities inhibit bacterial growth)
High urea concentration
High organic acid concentration
pH

Anti-adherence mechanisms
Bacterial

interference (naturally
endogenous bacteria in the urethra, vagina,
and periurethral region)
Urinary oligosaccharides (have the potential
to detach epithelial-bound E. coli
Tamm-Horsfall protein (uromucoid): coating
of E. coli by this protein might prevent
attachment

Miscellaneous
Mucopolysaccharide

lining of the

bladder
Urinary immunoglobulins
Spontaneous exfoliation of uroepithelial
cells with bacterial detachment
Mechanical flushing of micturition

Mechanisms of UTI

Pathway Of Renal Infection

HEMATOGENOUS INFECTION
Common agents :
Staphylococcus
E.coli
Bacteremia

AORTA

Intrarenal reflux

Vesicoureteral reflux

ASCENDING INFECTION
Common agents :
E.coli
Proteus
Enterobacter

Deranged vesicoureteral
junction
Bacteria enter bladder
Bacterial colonization

PATHOGENESIS
Gut flora
Uropathogens
Colonization
Barrier normal mucosa
Cystitis
BACTERIA VIRULENCE HOSTS IMMUNE DEFENCE
1. VUR
1. P-fimbrie
2. O & K serotype 2. Intrarenal Reflux
3. Haemolicine
3. Urinary tract obstruction
4. Colistine V
4. Foreign bodies (cateter )
5. Aerobactin
6. Bactericidal action resistant

Acute Pyelonephritis
scarring Urosepsis

Ascending

Mechanisms of lower UTI

Experimentally, 99.9% of a bladder

inoculum of bacteria is promptly excreted

by voiding.
Deficient antibodies in vaginal secretions;

and biochemical differences in receptors

on uroepithelial cells.

Mechanisms of upper UTI

Ascent

of bacteria from the bladder to the

kidneys is promoted by obstruction and by
reflux.

In

addition, motile bacteria can ascend

against the flow of a column of urine. Gramnegative bacteria (or endotoxin derived from
them) can inhibit ureteral peristalsis.

Localization: upper vs. lower

Indirect: pattern of recurrence (i.e., same

organism?); maximum urinary concentration;

water loading test; serum antibodies; cellular
excretion; urinary proteins
Direct: renal biopsy; ureteral catheterization;

antibody-coated bacteria test

Localization: upper vs. lower

(in practice)
Frequency, dysuria, and urgency lower

UTI symptoms.. sometime can occur with

upper UTI as well.
Fever and flank pain acute upper
urinary tract infection.
Scarring of the kidney by imaging
procedures suggests chronic UTI.
The distinction is sometimes difficult.

Acute cystitis
Characterized by sudden onset, multiple urinary

symptoms, pyuria, and sometimes hematuria

(uncommon)
Acute dysuria in young women usually indicates:
acute bacterial cystitis; the urethral syndrome; or
vaginitis
Causes: E. coli (80%), S. saprophyticus (10% to

15%), and occasionally Klebsiella, Proteus mirabilis,

and other microorganisms

Acute uncomplicated pyelonephritis

Largely a clinical diagnosis
Pyuria is usually present; about 20% have

positive blood cultures; causative organisms

the same as with cystitis
Predisposing factors: structural
abnormalities; strains of E. coli with unique
markers; genetically-determined
carbohydrate receptors on uroepithelial cells

Recurrent UTIs in women

Between 20% and 25% of young women

with acute uncomplicated cystitis have 2 or

more infections per year,
Usually due to reinfection with a different E.
coli strain
Predisposing factors: genetically-determined
receptors on uroepithelial cells.

Complicated UTIs
Definition: UTI in patients with

predisposing anatomic, functional, or

metabolic abnormalities
Spectrum of organisms is skewed toward

difficult-to-treat pathogens (e.g.,

Pseudomonas sp., yeasts, enterococci,
Enterobacteriaceae other than E. coli)

Catheter-associated UTI
Risk factors: female sex; duration of

catheterization; disconnecting the

junction between the catheter and the
collecting tube

Long-term bladder catheterization

Incidence

of significant bacteriuria in patients who

are not receiving antibiotics is 8% to 10% per day

More

than 85% of patients have at least two

strains of bacteria and 10% have more than five
strains

Some

species (notably, enterococci,

Pseudomonas, and Proteus) notoriously tend to
persist

Prostatitis
Relapsing

acute urinary tract infection in

men caused by the same bacterial species
often suggests chronic prostatitis with
periodic spill-over into the bladder
Symptoms: pelvic heaviness, rectal or
perineal pain, urinary hesitancy, dribbling,
and burning
A risk of catheterization

DIAGNOSIS

Diagnosis of UTI
History
Physical

exam (PE)

Lab
Urinalysis
Urine

culture
Sensitivity
Imaging

study

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

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

Diagnosis of UTI
Urinalysis
Bacteriuria

: bacteria identified on culture

Significant bacteriuria :
bacteria > 100.000 colony /ml fresh urine

Gold standard diagnostic UTI

Urine collection

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

Urinalysis
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

White blood cell casts

Highly

significant!
Presence

suggests
pyelonephritis

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

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

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

Prognosis
Adults
The

prognosis for most women with cystitis and

pyelonephritis is good; about 25% of women with
cystitis will experience a recurrence.
The prognosis for emphysematous pyelonephritis is
not as good and is discussed in Special Concerns.
Infected cysts in polycystic kidney disease respond
to treatment slowly.

Prognosis
Children
In industrialized countries, kidney damage with longterm complications as a consequence of urinary tract
infection per se is currently less common than in the
early 20th century, when pyelonephritis was a
frequent cause of hypertension and ESRD in young
women
This change is probably a result of improved overall
healthcare and close follow-up of children after an
episode of pyelonephritis.