Urinary Tract Infection (UTI)

Epidemiology of UTIs (USA)

8 million physician visits/ year

10.8% annual prevalence

40-50% lifetime prevalence in women

1 in 3 women – require antimicrobial therapy before 24 y/o

0.5-0.7 episodes/ person-year in sexually active women

$1 billion/ year for Evaluation, Treatment

Epidemiology of UTIs

↓ Prevalence in Men Greater Distance between

• Anus (source of organism)

• Urethral Meatus

Greater Length of Male Urethra Drier Environment surrounding male urethra

Risk Factors associated with UTI in Healthy Man Intercourse with Infected Female Partner

Homosexuality

Lack of Circumcision

Male Genitourinary System

Host Defence Mechanism

↓ pH Urine (Acidic)

↑ Urea, [Organic Acid]

Micturition (urination) – Flushing

Inflammatory response in GUT – Eradication of Bacteria

Prostatic Fluid – Inhibits Bacterial Growth

Antiadherence Urinary Mucus – Coats Bladder Epithelial Cells

Tamm-Hors fall Protein (Renal origin) – Glycoprotein that prevents organisms

from binding to mucosa

Classification – UTI

Lower Tract Upper Tract

Superficial, Mucosal Invasive

Urethritis Pyelonephritis

Cystitis Intrarenal, Perinephritic Abscess

Prostatitis

Epididymoorchitis

Classification – UTI

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, Recurrences

Causative Organisms

Community-Acquired Hospital-Acquired

Escherichia coli Escherichia coli

Klebsiella pneumoniae Pseudomonas aeroginosa

Proteus Mirabilis Proteus sp.

Staphylococcus saprophyticus Enterobacter sp.

Enterococcus faecalis Serratia sp.

Enterococcus sp.

Pathogenesis of Infection

Ascending Haematogenous Lymphatic

Female (95%) (common) Rare (<3%) Rare

Urethra colonized by Bacteria from Rectum, Vagina

ascend to bladder

Results from Bacteremia caused by relatively virulent

organisms

(eg. Salmonella, S. aureus)

Produce Focal Abscesses, areas of Pyelonephritis

within a Kidney

Result in +ve Urine Cultures

Pathogenesis

Vaginal Micro ecology

Alteration of Vaginal Microflora (facilitating vaginal colonization with coliforms)

Alteration in [Lactobacilli] (H2O2 producing strain) Factors that predispose to Vaginal Colonization also to Bladder Colonization

Sexual Intercourse, use of Diaphragm with Spermicide

(↑ Risk of E. coli vaginal colonization, Bacteriuria)

(Due to Alterations in Normal Vaginal Microflora)

Postmenopausal Women (changes in Vaginal Environment) Disappearance of previously predominant Lactobacilli (Vaginal Microflora)

↑ pH (alkaline)

↓ Prevalence of Vaginal E. coli colonization, Incide nce of UTI

Topical Estrogen Therapy (Restoration of Premenopausal Vaginal Flora)

Genetic Factors

Women with Recurrent UTI

• Persistent Vaginal Colonization with E. coli even in asymptomatic periods

• Vaginal, Periurethral Mucosal Cells bind Threefold ↑ Uropathogenic bacteria than women without recurrent infection

Women with Lewis Blood Group

• Epithelial cells may possess specific types or greater numbers of receptors

• Bind significantly greater numbers of bacteria

• Facilitating colonization - ↑ susceptibility

• Risk for Recurrent UTI

Bacterial Virulence Characteristics that have been associated with Uropathogenicity

• Antigen – Polysaccharide

• K Antigen – Antiphagocytic

• Siderophore Aerobactin – Resistance to Bactericidal activity of serum

• Toxins – Hemolysin, Cytotoxic Necrotizing Factor

• Adhesins (P Fimbriae) – mediate binding to specific receptors P fimbriae interact with specific receptor on epithelial cells

(Epithelial cell receptor – found in P blood group antigens)

Prevalence of P-fimbriated E. coli in Fecal Flora correlates with severity

↓ Prevalence

(10-20%)

↑ Prevalence

(50-60%)

Highest Prevalance

(70-100%)

Asymptomatic

Infection

Cause

Cystitis

Cause

Pyelonephritis

Healthy Patients with Pyelonephritis

(75-100% E. coli strains isolated from blood P fimbriae) Type 1 Pilus (adhesion structure) – all E. coli strains possess

Binding of Uropathogenic E. coli to Receptors

(initiates complex series of intracellular signalling events – alter epithelial cell

function, infla mmatory reaction)

Anatomic, Functional Abnormalities

Vesicoureteral Reflux, Ureteral Obstruction, Foreign Body

Lead to Incomplete Bladder Emptying, Inhibit Ureteral Peristalsis (stasis)

Pathogenesis – Summary Rectal, Vaginal Re servoirs

↓

Colonization of Per ianal Area

↓

Bacterial migrate to Perivaginal Area

↓

Bacteria Ascend t hrough Urethra to B ladder

↓

Intercourse may contribute to

Urethral Co lonization

Ascending Infection

UTI Mechanism

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Symptoms

Dysuria

Urgency

↑ Frequency

Hematuria

Suprapubic, Low Back Pain

Clinical Characteristics

Differential Diagnosis of Bacteriuria

Diagnosis of UTI

Urine Macroscopy

Urine Microscopy (Urine Analysis)

Urine Culture, Antibiotic Sensitivity Testing (Urine C&S)

Common Changes Found in Aged Urine

Urine Collection, Transportation

MSU

Catheterization (In, Out)

Suprapublic Aspiration

Urine Bag

Nephrostomy

Urine Microscopy

Urine is centrifuged – sediment – under ↑ Power Field – Leukocytes are count

↑ Leukocyte Count in Urine (>10/microliter) – Pyuria

Very accurate in identifying disease when it’s present

(But also Tests +ve in many people without UTI)

Diagnosis of UTI

Pyuria (non-hospitalized patients)

Presence of Standard Symptoms (Children – Fever)

Urine Culture

Urine is cultured on Cystine-Lactose-Electrolyte-Deficient (CLED) Medium

using UROSTRIP method

Plate is intubated at 37°C for 24h

UROSTRIP

Sterilized filter paper

Estimate amount of organisms present in urine

Interpretation

Significant Bacteriuria Asymptomatic Bacteriuria

Presence of 105 bacteria/ml

of Mid-Stream Urine Significant bacteriuria in patient without symptoms

Symptomatic (MSU) Asymptomatic (MSU) Catheterized Patients

≥ 105 CFU coliforms/ml

(95% probability True bacteriuria)

≥ 105 CFU bacteria/ml

on 2 consecutive specimens

(probability of True

bacteriuria – Single sp

80%, 2 sp. 95%)

≥ 102 CFU bacteria/ml

Mid-Stream Urine (MSU) Culture

Urine is frequently contaminated

Most common errors

Collecting a 1st

stream rather than a midstream sample (63%)

Placing one’s fingers inside the container or upon undersurface of lid (38%)

Failure to spread the labia away from stream of urine (67%)

Contact between Penis and Inside of Sterile Container (73%)

Common Contaminants

Coagulase-Negative Staphylococci (CoNS) Lactobacillus spp.

Diphtheroids

E. coli

Micrococci Viridans streptococci

Yeasts

Dipstick Test

Leukocyte Esterase

Leukocytes release Esterase in Urine

(Forming Indoxyl, which reacts with a diazonium salt to give a colour change)

Correlates well for detecting > 10WBC/hpf

Rapid screening test Sensitivity of 75-95%

Specificity of 65-95%

False –ve (common)(cause – unknown)

Nitrites

Bacteria (eg. Escherichia coli) convert nitrate – nitrite in Bladder

(Reacts with Napthylethylene – Colour Change) Require Bacteria in Urine in Bladder for 4-8h

(for enough conversion of Nitrate → Nitrite to be detectable)

Tests

-ve +ve

Organism is not nitrate-reducing Moderately Reliable

Enterococci False +ve

S. saprophyticus Old Voided (non-sterile collection)

of urine Acinetobacter

Ultrasound

Noninvasive

Risk-Free Imaging Test

Used to Screen Hydronephrosis

Kidney Stones

Abscesses

Nuclear Scans

Useful in certain complicated cases

Detect Kidney Scarring (after Pyelonephritis in Children)

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT)

Used when Nuclear Scans are Inconclusive

X-Rays with Contrast

Voiding Cystourethrogram Intravenous Pyelogram (IVP)

Detect Structural Abnormalities

Urethral Narrowing

Incomplete Bladder Emptying

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Uncomplicated UTI

Definition

No GU Abnormality

• Anatomy

• Function

• Metabolic Usually occur in otherwise Healthy Women

Common in Women throughout their lifespan

• Affect Typically 40-50% of Women

• Recent Onset < 65 y/o

• Single Pathogen

• E. coli (>80% of cases)

Pathogenesis

Ascending Uropathogens (E.coli, S. aprophyticus, Proteus spp., Klebsiella spp.)

Etiology in US (Women 15-50 y/o)

Gram Negative Gram Positive

Escherichia coli (72%) Enterococcus species (5%)

Klebsiella species (6%) Other Gram +ve species (7%)

Proteus species (4%)

Other (5%)

Treatment

Responds well to Treatment with Standard, Inexpensive Antimicrobial

TMP/ SMX resistance < 20% TMP/ SMX resistance > 10-20%

TMP/ SMX – 3 days Fluoroquinolone – 3 days

TMP – 3 days Nitrofurantoin – 7 days

Recurrent Uncomplicated UTIs

Pathogenesis Recurrent UTI due to Reinfection

(usually E. coli – not always from same strain as original infection)

Epidemiology

20-30% of Young Wome n with Uncomplicated Cystitis have Recurrent UTI

Risk Factors

• Sexual Intercourse

• Spermicide

• 1st

UTI at early age

• Maternal history of UTI

Treatment

Long-Term Post-Intercourse Self-Treatment

Diagnosis (3 days)

↓ Dose Prophylaxis

(6-12 months)

↓ Dose Prophylaxis TMP/ SMX

Single Dose TMP

TMP TMP/ SMX Fluoroquinolone

Nitrofurantoin TMP

Norfloxacin Nitrofurantoin

Cephalexin

Fluoroquinolone

Self-Diagnosis, Treatment of Recurrent UTI Study to determine accuracy, efficacy

Patient-Initiated Treatment of Recurrent UTI

Treated with

• Ofloxaci n 200mg BID for 3 days

• Levofloxacin 250 mg QD for 3 days Urine samples

• 84% of self-diagnosed cases were culture +ve

• 11% were sterile pyuria Self-Treated cases result in

• 92% Clinical Cure

• 96% Microbiological Cure

Complicated UTI

Definition

Urinary Tract Infection with Abnormal Urinary Tract

• Functionally

• Metabolically

• Anatomically Abnormality Include

• Foreign Body (Catheter, Stent)

• Obstruction (Calculi, Congenital Anomaly, Prostatic Disease, Stricture, Tumour)

Epidemiology/ Pathogenesis

UTI Men 16-35 y/o (most common) Nosocomial Infection (most common)

• Catheter-related UTI (31% of Hospital-Acquired Infections)

• Prolongs Hospital Stay

• ↑HospitalizaRon costs

E. coli ↓ common (compared to Uncomplicated UTI)

Risk Factors

Advanced Age, Debility

Hospitalization

Long-Term Care

Diabetes Mellitus

Functional/ Anatomical Abnormalities

Immunosuppression, Suppressive Drugs

Pregnancy, Menopause

Catheter, Stent

Stones in Bladder, Urinary Tract

Recent Antibiotic use

Recent Urinary Tract Instrumentation

Renal Transplant

Clinical Implications

Pathogens – wide range of Gram –ve, Gram +ve

Resistance to TMP/ SMX common

Therapy – 7-14 days of Antimicrobial Therapy

Follow up – Repeat Urinalysis, Culture

(1-2 weeks after completion of Antibiotic Therapy)

Etiology

Bacterial Uropathogen Prevalence in Complicated UTI (%)

Escherichia coli 21 – 54

Klebsiella pneumoniae 1.9 – 17

Enterobacter species 1.9 – 9.6

Citrobacter species 4.7 – 6.1

Proteus mirabilis 0.9 – 9.6

Providencia species 18

Pseudomonas aeruginosa 2 – 19

Enterococci species 6.1 - 23

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Acute Pyelonephritis

Epidemiology

250,000 patients/ year in US

Pathogenesis

Infection of Upper Urinary Tract

Implicated Pathogens

• Escherichia coli

• Proteus Mirabilis

• Klebsiella pneumoniae

Symptoms (May develop rapidly <24h) Fever > 38°C

Chills

Nausea/ Vomiting

Diarrhoea Symptoms of Cystitis

Generalized Muscle Tenderness

Flank Pain

Treatment

(Eradicate Pathogens in Kidney, Urothelium)

(Treat/ Prevent Bacteremia)

Hospitalized Patients – IV Antibiotic 1st

48-72h, followed by 7d Oral Antibiotic

• Fluoroquinolone IV, then PO

• Aminoglycoside + Ampicillin IV then TMP/SMX PO or amox/ clav

• 3rd

Generation Cephalosporin IV

then TMP/SMX PO or amox/ clav Ambulatory Patients – 7-14d of PO therapy (with 1 of Antimicrobials above)

Prostatitis

Epidemiology

1/3 of Men will have episode of Bacteruria by 8th

decade

50% of Men will have Symptoms

25% will be diagnosed with one of the prostatitis syndromes Most common Urologic Problem in Men < 50 y/o

Category

I II III IV

Acute

Bacterial

Prostatitis (1-5%)

Chronic

Bacterial

Prostatitis (5-10%)

IIIA IIIB Asymptomatic

Inflammatory

Prostatitis

Chronic

Nonbacterial

Prostatitis

(Inflammatory)

Chronic Pelvic

Pain

Syndrome

(Non-Inflammatory)

Acute Bacterial Prostatitis Chronic Bacterial Prostatitis

Symptoms

Characterized by

• Symptoms of UTI

• +ve Urine o Prostatic Secretion

o Inflammatory Cells Acute Presentation (Men - 40-60 y/o)

Warm, Tender Prostate

Organisms typically seen in UTIs

Ascending route of Infection Responds favourably to Antibiotics

Present similar to Relapsing UTI even

after appropriate antibiotic therapy Seen in Men 50-80 y/o

Characterized by

• Dysuria

• Voiding complains

• Ejaculatory Pain

• Nonspeci fic Pelvic Pain Response to Antibiotics may be slow

(but predictable)

Treatment

• Co-Trimoxazole

(DS 1 tab twice daily 4-6 weeks)

• Ciprofloxaci n (500mg PO twice daily (4-6 weeks

• Ampicillin (2gm every 6h) + Gentamicin (5mg/kg)

in divided doses

(if enterococcus suspected)

Treatment

• Fluoroquinolone

(Oral, 4-8 weeks)

• Co-Trimoxazole (DS BID PO, 4-8 weeks)

• Doxycycline (100mg PO BID, 4-8 weeks)

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