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Urinary Tract Infection (UTI)

Epidemiology of UTIs (USA) Pathogenesis of Infection

8 million physician visits/ year Ascending Haematogenous Lymphatic
10.8% annual prevalence Female (95%) (common ) Rare (<3%) Rare
40-50% lifetime prevalence in women Urethra colonized by Results from Bacteremia
1 in 3 women – require antimicrobial therapy before 24 y/o Bacteria from Rectum, Vagina caused by relatively virulent
0.5-0.7 episodes/ person-year in sexually active women ascend to bladder organisms
$1 billion/ year for Evaluation, Treatment (eg. Salmonella, S. aureus)
Produce Focal Abscesses,
Epidemiology of UTIs areas of Pyelonephritis
↓ Prevalence in Men within a Kidney
Greater Distance between Result in +ve Urine Cultures
• Anus (source of organism)
• Urethral Meatus Pathogenesis
Greater Length of Male Urethra Vaginal Micro ecology
Drier Environment surrounding male urethra Alteration of Vaginal Microflora (facilitating vaginal colonization with coliforms)
Risk Factors associated with UTI in Healthy Man Alteration in [Lactobacilli] (H2O2 prod ucing strain)
Intercourse with Infected Female Partner Factors that predispose to Vaginal Colonization also to Bladder Colonization
Homosexuality Sexual Intercourse, use of Diaphragm with Spermicide
Lack of Circumcision (↑ Risk of E. coli vaginal colonization, Bacteriuria)
(Due to Alterations in Normal Vaginal Microflora)
Male Genitourinary System Postmenopausal Women (changes in Vaginal Environment)
Disappearance of previously predominant Lactobacilli (Vaginal Microflora)
↑ pH (alkaline)
↓ Prevalence of Vaginal E. coli colonization, I ncide 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
Host Defence Mechanism ↓ Prevalence ↑ Prevalence Highest Prevalance
↓ pH Urine (Acidic) (10-20%) (50-60%) (70-100%)
↑ Urea, [Organic Acid] Asymptomatic Cause Cause
Micturition (urination) – Flushing Infection Cystitis Pyelonephritis
Inflammatory response in GUT – Eradication of Bacteria Healthy Patients with Pyelonephritis
Prostatic Fluid – Inhibits Bacterial Growth (75-100% E. coli strains isolated from blood P fimbriae)
Antiadherence Type 1 Pilus (adhesion structure) – all E. coli strains possess
Urinary Mucus – Coats Bladder Epithelial Cells Binding of Uropathogenic E. coli to Receptors
Tamm-Hors fall Protein (Renal origin) – Glycoprotein that prevents organisms (initiates complex series of intracellular signalling events – alter epithelial cell
from binding to mucosa function, infla mmatory reaction)
Anatomic, Functional Abnormalities
Classification – UTI Vesicoureteral Reflux, Ureteral Obstruction, Foreign Body
Lower Tract Upper Tract Lead to Incomplete Bladder Emptying, Inhibit Ureteral Peristalsis (stasis)
Superficial, Mucosal Invasive
Urethritis Pyelonephritis Pathogenesis – Summary
Cystitis Intrarenal, Perinephritic Abscess Rectal, Vaginal Re servoirs
↓
Prostatitis Coloni zation of Per ianal Area
Epididymoorchitis ↓
Bacterial migrate to Perivaginal Area
↓
Classification – UTI Bacteria Ascend t hrough Urethra to B ladder
↓
Uncomplicated Complicated Intercourse may contribute to
Not due to functional or structural Due to Predisposing Lesion Urethral Co loni zation
Ascending Infection
abnormality
Short course of Therapy Longer course of Therapy
UTI Mechanism
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 s p.
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Symptoms Mid-Stream Urine (MSU) Culture

Dysuria Urine is frequently contaminated
Urgency Most common errors
↑ Frequency Collecting a 1st stream rather than a midstream sample (63%)
Hematuria Placing one’s fingers inside the container or upon undersurface of lid (38%)
Suprapubic, Low Back Pain Failure to spread the labia away from stream of urine (67%)
Contact between Penis and Inside of Sterile Container (73%)
Clinical Characteristics Common Contaminants
Coagulase-Negative Staphylococci (CoNS)
Lactobacillus spp.
Diphtheroids
E. coli
Micrococci
Viridans streptococci
Yeasts

Dipstick Test
Leukocyte Esterase
Leukocytes release Esterase in Urine
Differential Diagnosis of Bacteriuria (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)
Diagnosis of UTI Require Bacteria in Urine in Bladder for 4-8h
Urine Macroscopy (for enough conversion of Nitrate → Nitrite to be detectable)
Urine Microscopy (Urine Analysis) Tests
Urine Culture, Antibiotic Sensitivity Testing (Urine C&S) -ve +ve
Organism is not nitrate-reducing Moderately Reliable
Common Changes Found in Aged Urine Enterococci False +ve
S. saprophyticus Old Voided (non-sterile collection)
Acinetobacter of urine

Ultrasound
Noninvasive
Risk-Free Imaging Test
Used to Screen
Hydronephrosis
Kidney Stones
Abscesses

Urine Collection, Trans portation Nuclear Scans

MSU Useful in certain complicated cases
Catheterization (In, Out) Detect Kidney Scarring (after Pyelonephritis in Children)
Suprapublic Aspiration
Urine Bag Magnetic Resonance Imaging (MRI) or Computed Tomography (CT)
Nephrostomy Used when Nuclear Scans are Inconclusive

Urine Microscopy X-Rays with Contrast

Urine is centrifuged – sediment – under ↑ Power Field – Leukocytes are count Voiding Cystourethrogram
↑ Leukocyte Count in Urine (>10/microliter) – Pyuria Intravenous Pyelogram (IVP)
Very accurate in identifying disease when it’s present Detect
(But also Tests +ve in many people without UTI) Structural Abnormalities
Diagnosis of UTI Urethral Narrowing
Pyuria (non-hospitalized patients) Incomplete Bladder Emptying
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 Significant bacteriuria in patient
of Mid-Stream Urine without symptoms
Symptomatic (MSU) Asymptomatic (MSU) Catheterized Patients
≥ 105 CFU coliforms/ml ≥ 105 CFU bacteria/ml ≥ 102 CFU bacteria/ml
(95% probability True on 2 consecutive
bacteriuria) specimens
(probability of True
bacteriuria – Single sp
80%, 2 sp. 95%)
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Uncomplicated UTI Complicated UTI

Definition Definition
No GU Abnormality Urinary Tract Infection with Abnormal Urinary Tract
• Anatomy • Functionally
• Function • Metabolically
• Metabolic • Anatomically
Usually occur in otherwise Healthy Women Abnormality Include
Common in Women throughout their lifespan • Foreign Body (Catheter, Stent)
• Affect Typically 40-50% of Women • Obstruction
• Recent Onset < 65 y/o (Calculi, Congenital Anomaly, Prostatic Disease, Stricture, Tumour)
• Single Pathogen Epidemiology/ Pathogenesis
• E. coli (>80% of cases) UTI Men 16-35 y/o (most common )
Pathogenesis Nosocomial Infection (most common )
Ascending Uropathogens (E.coli, S. aprophyticus, Proteus spp., Klebsiella spp.) • Catheter-related UTI (31% of Hospital-Acquired Infections)
Etiology in US (Women 15-50 y/o) • Prolongs Hospital Stay
Gram Negative Gram Positive • ↑HospitalizaRon costs
Escherichia coli (72%) Enterococcus s pecies (5%) E. coli ↓ common (compared to Uncomplicated UTI)
Klebsiella species (6%) Other Gram +ve species (7%) Risk Factors
Proteus species (4%) Advanced Age, Debility
Other (5%) Hospitalization
Treatment Long-Term Care
Responds well to Treatment with Standard, Inexpensive Antimicrobial Diabetes Mellitus
TMP/ SMX resistance < 20% TMP/ SMX resistance > 10-20% Functional/ Anatomical Abnormalities
Immunosuppression, Sup pressive Drugs
TMP/ SMX – 3 days Fluoroquinolone – 3 days
Pregnancy, Menopause
TMP – 3 days Nitrofurantoin – 7 days
Catheter, Stent
Stones in Bladder, Urinary Tract
Recurrent Uncomplicated UTIs
Recent Antibiotic use
Pathogenesis Recent Urinary Tract Instrumentation
Recurrent UTI due to Reinfection Renal Transplant
(usually E. coli – not always from same strain as original infection) Clinical Implications
Epidemiology Pathogens – wide range of Gram –ve, Gram +ve
20-30% of Young Wome n with Uncomplicated Cystitis have Recurrent UTI Resistance to TMP/ SMX common
Risk Factors Therapy – 7-14 days of Antimicrobial Therapy
• Sexual Intercourse Follow up – Repeat Urinalysis, Culture
• Spermicide (1-2 weeks after completion of Antibiotic Therapy)
• 1st UTI at early age Etiology
• Maternal history of UTI Bacterial Uropathogen Prevalence in Complicated UTI (%)
Treatment Escherichia coli 21 – 54
Self-Treatment Klebsiella pneumoniae 1.9 – 17
Long-Term Post-Intercourse
Diagnosis (3 days) Enterobacter species 1.9 – 9.6
↓ Dose Prophylaxis ↓ Dose Prophylaxis TMP/ SMX Citrobacter species 4.7 – 6.1
(6-12 months) Single Dose TMP Proteus mirabilis 0.9 – 9.6
TMP TMP/ SMX Fluoroquinolone Providencia species 18
Nitrofurantoin TMP Pseudomonas aeruginosa 2 – 19
Norfloxacin Nitrofurantoin Enterococci species 6.1 - 23
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
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Acute Pyelonephritis Prostatitis

Epidemiology Epidemiology
250,000 patients/ year in US 1/3 of Men will have episode of Bacteruria by 8th decade
Pathogenesis 50% of Men will have Symptoms
Infection of U pper Urinary Tract 25% will be diagnosed with one of the prostatitis syndromes
Implicated Pathogens Most common Urologic Problem in Men < 50 y/o
• Escherichia coli Category
• Proteus Mirabilis I II III IV
• Klebsiella pneumoniae Acute Chronic IIIA IIIB Asymptomatic
Symptoms (May develop rapidly <24h) Bacterial Bacterial Chronic Chronic Pelvic Inflammatory
Fever > 38°C Prostatitis Prostatitis Nonbacterial Pain Prostatitis
Chills (1-5%) (5-10%) Prostatitis Syndrome
Nausea/ Vomiting (Inflammatory) (Non-
Diarrhoea Inflammatory)
Symptoms of Cystitis Acute Bacterial Prostatitis Chronic Bacterial Prostatitis
Generalized Muscle Tenderness Symptoms Present similar to Relapsing UTI even
Flank Pain Characterized by after appropriate antibiotic therapy
Treatment • Symptoms of UTI Seen in Men 50-80 y/o
(Eradicate Pathogens in Kidney, Urothelium) • +ve Urine Characterized by
(Treat/ Prevent Bacteremia) o Prostatic Secretion • Dysuria
Hospitalized Patients – IV Antibiotic 1st 48-72h, followed by 7d Oral Antibiotic o Inflammatory Cells • Voiding complains
• Fluoroquinolone IV, then PO Acute Presentation (Men - 40-60 y/o) • Ejaculatory Pain
• Aminoglycoside + Ampicillin IV Warm, Tender Prostate • Nonspeci fic Pelvic Pain
then TMP/SMX PO or amox/ clav Organisms typically seen in UTIs Response to Antibiotics may be slow
• 3rd Generation Cephalosporin IV Ascending route of Infection (but predictable)
then TMP/SMX PO or amox/ clav Responds favourably to Antibiotics
Ambulatory Patients – 7-14d of PO therapy (with 1 of Antimicrobials above) Treatment Treatment
• Co-Trimoxazole • Fluoroquinolone
(DS 1 tab twice daily 4-6 weeks) (Oral, 4-8 weeks)
• Ciprofloxaci n • Co-Trimoxazole
(500mg PO twice daily (4-6 weeks (DS BID PO, 4-8 weeks)
• Ampicillin (2gm every 6h) + • Doxycycline
Gentamicin (5mg/kg) (100mg PO BID, 4-8 weeks)
in divided doses
(if enterococcus sus pected)