Urinary Tract Infection

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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

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 Superficial, Mucosal Urethritis Cystitis Prostatitis Epididymoorchitis

Upper Tract Invasive Pyelonephritis Intrarenal, Perinephritic Abscess

Pathogenesis of Infection Ascending Female (95%) (common ) Urethra colonized by Bacteria from Rectum, Vagina ascend to bladder

Haematogenous Rare ( 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) Acinetobacter of urine Ultrasound Noninvasive Risk-Free Imaging Test Used to Screen Hydronephrosis Kidney Stones Abscesses

Urine Collection, Trans portation MSU Catheterization (In, Out) Suprapublic Aspiration Urine Bag Nephrostomy

Nuclear Scans Useful in certain complicated cases Detect Kidney Scarring (after Pyelonephritis in Children)

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)

X-Rays with Contrast Voiding Cystourethrogram Intravenous Pyelogram (IVP) Detect Structural Abnormalities Urethral Narrowing Incomplete Bladder Emptying

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%)

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Used when Nuclear Scans are Inconclusive

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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 s pecies (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 Self-Treatment Long-Term Post-Intercourse Diagnosis (3 days) ↓ Dose Prophylaxis ↓ Dose Prophylaxis TMP/ SMX (6-12 months) 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, Sup pressive 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 U pper Urinary Tract Implicated Pathogens • Escherichia coli • Proteus Mirabilis • Klebsiella pneumoniae Symptoms (May develop rapidly 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 Chronic IIIA IIIB Asymptomatic Bacterial Bacterial Chronic Chronic Pelvic Inflammatory Prostatitis Prostatitis Nonbacterial Pain Prostatitis (1-5%) (5-10%) Prostatitis Syndrome (Inflammatory) (NonInflammatory) Acute Bacterial Prostatitis Chronic Bacterial Prostatitis Symptoms Present similar to Relapsing UTI even Characterized by after appropriate antibiotic therapy Seen in Men 50-80 y/o • Symptoms of UTI Characterized by • +ve Urine o Prostatic Secretion • Dysuria o Inflammatory Cells • Voiding complains Acute Presentation (Men - 40-60 y/o) • Ejaculatory Pain Warm, Tender Prostate • Nonspeci fic Pelvic Pain Organisms typically seen in UTIs Response to Antibiotics may be slow Ascending route of Infection (but predictable) Responds favourably to Antibiotics 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)