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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

Homosexuality Lack of Circumcision Male Genitourinary System Host Defence Mechanism ↓ pH Urine (Acidic) ↑ Urea,

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-Horsfall 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 toVaginal Colonization alsoto 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 withE. 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

↑ Prevalence

Highest Prevalance

(10-20%)

(50-60%)

(70-100%)

Asymptomatic

Cause

Cause

Infection

Cystitis

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

hrough Urethra to B ladder ↓ Intercourse may contribute to Urethral Co lonization Ascending Infection UTI

Symptoms

Dysuria

Urgency

↑ Frequency

Hematuria

Suprapubic, Low Back Pain

Clinical Characteristics

Suprapubic, Low Back Pain Clinical Characteristics Differential Diagnosis of Bacteriuria Diagnosis of UTI

Differential Diagnosis of Bacteriuria

Characteristics Differential Diagnosis of Bacteriuria Diagnosis of UTI Urine Macroscopy Urine Microscopy

Diagnosis of UTI

Urine Macroscopy

Urine Microscopy (Urine Analysis)

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

Common Changes Found in Aged Urine

Testing (Urine C&S) Common Changes Found in Aged Urine Urine Collection, Transportation MSU Catheterization

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 10 5 bacteria/ml of Mid-Stream Urine

Significant bacteriuria in patient without symptoms

Symptomatic(MSU)

Asymptomatic (MSU)

Catheterized Patients

≥ 10 5 CFU coliforms/ml (95% probability True bacteriuria)

≥ 10 5 CFU bacteria/ml on 2 consecutive specimens (probability of True bacteriuria – Single sp 80%, 2 sp. 95%)

≥ 10 2 CFU bacteria/ml

Mid-Stream Urine (MSU) Culture

Urine is frequently contaminated

Most common errors Collecting a 1 st 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

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 withStandard, 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

1 st 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

↑Hospitaliza on 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

Acute Pyelonephritis

Prostatitis

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 1 st 48-72h, followed by 7d Oral Antibiotic

Fluoroquinolone IV, then PO

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

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

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

Chronic

IIIA

IIIB

Asymptomatic

Bacterial

Bacterial

Chronic

Chronic Pelvic

Inflammatory

Prostatitis

Prostatitis

Nonbacterial

Pain

Prostatitis

(1-5%)

(5-10%)

Prostatitis

Syndrome

(Inflammatory)

(Non-

Inflammatory)

Acute Bacterial Prostatitis

 

Chronic Bacterial Prostatitis

Symptoms Characterized by

 

Present similar to Relapsing UTI even after appropriate antibiotic therapy

Symptoms of UTI

Seen in Men 50-80 y/o

+ve Urine

Characterized by

 

o

Prostatic Secretion

Dysuria

o

Inflammatory Cells

Voiding complains

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

Ejaculatory Pain

 

Warm, Tender Prostate Organisms typically seen in UTIs Ascending route of Infection Responds favourably to Antibiotics

Nonspeci fic Pelvic Pain

Response to Antibiotics may be slow

(but predictable)

 

Treatment

Treatment

 
 

Co-Trimoxazole (DS 1 tab twice daily 4-6 weeks)

Fluoroquinolone (Oral, 4-8 weeks)

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

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

Ampicillin (2gm every 6h) + Gentamicin (5mg/kg) in divided doses (if enterococcus suspected)

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