L75: Urinary Tract Infections

Question 1

Epidemiology of UTI

Answer 1

• Adult women: 25% by age 30
• Adult men: rare
• Female to male = 30:1
• 30-40%: Hospital-acquired due to use of catheters
• bacteraemia, chronic renal failure, renal stones

Question 2

Host defences in UTI

Answer 2

1. Flushing effect of urine
2. Humoral immunity
3. Cell-mediated immunity

Question 3

Host-microbe interaction

Answer 3

1. Entry
2. Adhesion / Colonisation
3. Spread + Multiplication
4. Damage

Question 4

Microbe entry in UTI

Answer 4

Microbial factors:
- Ascend from urethra
- Enteric / Skin bacteria:
—> E. coli (UPEC/ExPEC)
—> Staphylococcus saprophyticus
—> Enterococci
—> Proteus mirabilis

Question 5

Host factors in microbial entry

Answer 5

• Length of urethra
• Mechanical factors (catheter, trauma)
• Genetic factors
• Hormonal effect (atrophic effect)
• Underlying disease

Question 6

Virulence factors of main uropathogens

Answer 6

1. Adherence (pili, adhesin)
2. Toxin
3. Immune evasion (capsule, elastase)
4. Iron acquisition

Question 7

UPEC / ExPEC virulence factors

Answer 7

1. Type 1 and P Fimbriae
2. LPS (Lipid A+ polysaccharide (O-antigen + Core))
3. Capsular polysaccharide
4. Toxin:
   - Hemolysin
   - Aerobactin
   - Protease

Question 8

Microbial spread in UTI

Answer 8

• Bladder —> kidney —> blood
  1. Reflux (Incompetent ureterovesical valves)
  2. Poor emptying (neurogenic bladder)
  3. Dilatation / Decreased peristalsis of ureter (Pregnancy)
  4. Nidus for persistence (Catheter)
  5. Obstruction (stones)
  6. Immune incompetence (DM)

Question 9

Microbial damage in UTI

Answer 9

1. Polysaccharide capsule: inhibit phagocytosis
2. LPS: inflammation
3. Haemolysin: tissue damage
4. Urease: stone formation (urea —> NH3: precipitation of salt due to ↑ pH)

Question 10

***Uncomplicated UTI vs Complicated UTI

Answer 10

Uncomplicated UTI:

• Infection in structurally and neurologically normal UT / Health individuals
  1. UPEC
  2. S. saprophyticus
  3. K. pneumoniae
  4. Enterococcus

Complicated UTI:

• Compromised UT/ host defence / Infection in men, pregnant women, children
  1. UPEC
• 2. Enterococcus
     
     3. K. pneumoniae
• 4. Candida spp.

Question 11

***UTI syndrome

Answer 11

1. Acute pyelonephritis (high fever, loin pain)
2. Perinephric abscess (extension of pus through renal capsule into perinephric tissue)
3. Cystitis (frequency, dysuria, suprapubic discomfort)
4. Prostatitis (fever, perineal pain)
5. Asymptomatic bacteriuria
6. Urethritis
   * ** glomerulonephritis is autoimmune (x infection)

Question 12

Recurrent, Relapse, Reinfection, Urosepsis

Answer 12

Recurrent: relapse / reinfection

Relapse: same bacterial stain, consequence of bacterial persistence

Reinfection: new infection by a different strain

Urosepsis: sepsis caused by UTI

Question 13

Microbiological diagnosis

Answer 13

1. Bacteria culture (pyruria, significant bacteriuria)
   —> Quantitation / Semi-quantitative culture
   - differentiate contamination / genuine bacteriuria
   - standard loop
   - paper strip
   - dip slide
   - CLED agar (Cystiene, Lactose, Electrolyte Deficient agar: prevent Proteus swarming —> isolation and differentiation of urinary microbes)
2. Urine dipstick
   —> Nitrite detection
   - reduce nitrate to nitrite
   - pink colour
   - for Staphylococcus, Enterobacteriaceae, Proteus, Pseudomonas
   - negative does not rule out: bacteria do not have the enzyme / urine not retained long enough
   —> Leukocyte detection
   - leukocyte esterase
   - purple colour
   - drugs may interfere with chemical reaction: false negative
   - contamination / vaginal discharge: false positive

Question 14

Interpretation of significant bacteriuria

Answer 14

• Suprapubic tap urine: any growth
• Indwelling urine catheter: >10^5 cfu / ml plus symptoms
• Pediatric urine bag: >10^5 cfu / ml (caution)
• Clean-catch urine: >10^5 cfu / ml (caution)
• Mid-stream urine: >10^5 cfu / ml x 2 sample if no symptoms

Symptomatic patients without >10^5 cfu / ml:

• uncomplicated cystitis
• male patients
• pure growth (E. Coli) —> lower colony counts but may still be clinically significant

Question 15

Specimen collection

Answer 15

1. Avoid cleaning with antiseptic (false negative)
2. Whip in backward direction

False positive:

• heavy colonisation of vagina
• delayed transport

Question 16

Treatment of bacteriuria

Answer 16

• NO symptom = NO treatment
• since common in elderly, debilitated
• no urine culture if no symptom
• giving antibiotic may selective for resistant bacteria
• recurrence common after treatment

Asymptomatic but still need treatment:

1. Pregnant women
2. Before urological operation
3. Children < 5 (when associated with vesicoureteric reflux)

Question 17

Recurrent UTI

Answer 17

• **- 1 in 10 women
• most do NOT have structural abnormality
• behavioural factors
• receptive uroepithelial cells / colonisation by “stick strain” E. coli
• Urological evaluation not needed unless Recurrent + >= 1 red flag signs:
  1. Haematuria (between infection)
  2. Pyelonephritis
  3. Obstructive symptoms
  4. Urea-splitting bacteria
  5. Urine stone
  6. Severe diabetes

Question 18

Acute Prostatitis

Answer 18

Risk factors:

• unprotected anal intercourse
• catheter use
• prostate biopsy

Symptoms:

• Dysuria, frequency
• High fever
• Urinary retention
• Tender prostate

Culture: yield pathogen >10^5 cfu / ml (often E. coli)

Question 19

Chronic bacterial prostatitis

Answer 19

• Relapsing UTI by same organism
• causes: instrumentation, dysfunctional voiding, retrograde spread into prostatic duct
• Positive 4/2 glass test
• 4 glass test (1 log higher count): collect 1st 10ml voided urine after prostatic massage
  —> difficult to perform, limited sensitivity for gram +ve
• 2 glass test: collect semen, repeat if ejaculate yield gram +ve bacteria
  —> easier to perform, better sensitivity for gram +ve

Accepted pathogens

• E. coli
• Enterobacteriaceae
• Enterococci
• P. aeruginosa

Treatment: 6 weeks antibiotics