Urology JC073: I Have Pain When I Pass Urine: Urinary Tract Infection Including Tuberculosis

Question 1

UTI

Answer 1

**Inflammatory response of urothelium to invasion by **bacteria / other pathogens
- usually associated with **bacteriuria, **pyuria (WBC in urine)

Result of interaction between host + uropathogens
1. Host
- Defence mechanisms
- Inherent susceptibility to UTI

2. Uropathogens
   - Virulence
   - Inoculum size

One of commonest bacterial infection:
- 30% women have symptomatic UTI by age of 24
- 50% women experience UTI during lifetime
- enormous cost to health system

Incidence:
- More common in women (∵ shorter urethra (2-3 cm) —> bacteria travel more easily)
- ↑ with age
- sharp ↑ in late adolescence (***onset of sexual activity) and 20-40 yo
- prevalence of bacteriuria in young women 30x than men —> ratio ↓ with age

Question 2

Bacteriuria vs Pyuria

Answer 2

Bacteriuria:
- Presence of bacteria in urine
- ***NOT equal to UTI
- DDx: colonisation, contamination
- Symptomatic vs Asymptomatic

Pyuria:
- Presence of **WBC in urine
- Indicative of **infection / inflammatory response of urinary tract
- **NOT equal to UTI
- DDx: **urolithiasis, **malignancy, **TB infection (記: Stone, Malignancy, Infection)

Question 3

***Natural defence of UT

Answer 3

1. Normal flora (periurethral area, introitus, vagina)
   - ***Lactobacilli (glycogen —> lactic acid) produces low vaginal pH
   - Vaginal environment related to Estrogen + Cervical IgA

Alterations:
- **Hypoestrogenised states (e.g. menopause)
- **Spermicidal agents
- ***Antimicrobial use
—> alters amount of Lactobacilli

2. Urine
   - **Antegrade flow of urine
   - Physical + Chemical characteristics unfavourable for UTI
   —> normal pH
   —> **high osmolality
   —> ***Tamm-Horsfall protein (from tubular cells of ascending LoH —> saturates mannose-binding sites of type 1 pili of pathogens)

Alterations:
- ***UT obstruction

3. Bladder
   - normal emptying of bladder urine (at low pressure)
   - normal **exfoliation of urothelial cells
   - receptors on **superficial urothelial cells recognise LPS + active innate immunity (↑ local PMN leukocytes, macrophages —> local inflammation)

Alterations:
- **Bladder outlet obstruction
- **Neurogenic bladder (loss of function of normal emptying)
- Bladder diverticulum (dead space with urine inside)
- **Indwelling catheter (bacteria get short-cut to bladder)
- **Vesicoureteral reflux

Question 4

Inherent susceptibility to UTI

Answer 4

**Vaginal cells’ susceptibility of bacterial adherence
- **genetically determined
- directly affects rate of recurrent UTI

**Lewis blood group
- determines ability of cellular **fucosylation —> affect bacterial **adherence
- Le (a-b-) / Le (a+b-) —> associated with higher incidence of recurrent UTI
- non-secretor status (Le **b-) —> associated with premenopausal acute pyelonephritis (easier access by bacteria to climb up ureter to kidney)

Question 5

Bacterial virulence

Answer 5

Characteristics of uropathogens that allow them to colonise + invade UT

Factors against host
1. **Adhesins (Bacterial adherence mechanisms)
2. **Toxins
- Haemolysin HlyA: forms pores in host cell membrane + erythrocyte lysis
3. **Urease
- breaks down urea into ammonia (favourable for uropathogens to reproduce)
4. Others
- **IgA inactivating protein
- ***Phasic variation of piliated state (to escape host defence mechanism)

Factors against external agents
- e.g. Antimicrobial resistance

Question 6

1. Bacterial adherence mechanisms / Adhesins

Answer 6

Fimbrial vs Afimbrial

Fimbrial adhesins (Pili) (記: **PS1):
1. **Type 1 (mannose-sensitive) pili (FimH, FimA)
- commonest pili expressed by E. coli
- found in majority of isolates from acute ***cystitis

2. **Type P (mannose-resistant) pili (PapG, X-adhesion)
   - binds preferentially to **upper tract urothelium
   - found in 80% of isolate from acute ***pyelonephritis
3. ***Type S
   - both bladder + kidney infection

Afimbrial adhesins:
- Dr adhesins family

Question 7

Pathogenesis of UTI

Answer 7

3 important steps:
1. Bacterial adherence (onto urothelium / vaginal epithelium)
2. Bacterial colonisation / ascension
3. Bacterial invasion
—> Clinical UTI (characterised by presence of host inflammatory response)

Question 8

Routes of infection

Answer 8

1. Ascending route
   - commonest
   - rectum —> urethra —> bladder —> may ascend to kidney (pyelonephritis)
   - facilitated by
   —> **Indwelling catheter
   —> **Vesicourethral reflux
   —> ***Ureteral / Urethral obstruction
2. Haematogenous route
   - uncommon in normal individual
   - kidneys secondarily infected by extrarenal source of bacteria e.g. S. aureus
   - e.g. **Renal abscesses from **septic emboli, ***GUTB
3. Direct extension / Contiguous spread
   - from neighbouring suppurative infections (e.g. abscess in ***retroperitoneum)
   - unusual

Question 9

***Microbiology of UTI

Answer 9

***Facultative anaerobes (most, usually from bowel flora)

Community-acquired UTI:
- **E. coli (85%)
- **Proteus
- **Klebsiella spp.
- **Enterococcus
- ***Staphylococcus saprophyticus (10% of acute cystitis in young sexually active females)

Nosocomial UTI:
- **E. coli (50%)
- can be **polymicrobial
- ***Pseudomonas, Citrobacter, Providencia, Serratia, Enterobacter spp., Coagulase-negative Staphylococcus (normally harmless unless immunocompromised)

Anaerobes:
- ***Suppurative infection
- ~80% of scrotal, prostatic, perinephric abscess

Question 10

Diagnosis of UTI

Answer 10

1. Clinical S/S
2. ***Urinalysis
3. ***Urine culture

Can be a diagnostic challenge sometimes (e.g. elderly)

Urine collection methods (↑ in invasiveness but ↓ contamination risk):
1. ***MSU (commonest)
- prone to contamination (up to 1/3 specimens in female patients)

2. **Urethral catheterisation (CSU)
   - “Cath-once”
   - not indicated in men unless cannot void
   - may be used in females to avoid contamination
   - risk of **introduction of UTI
3. ***Suprapubic aspiration
   - most accurate method
   - indicated in paediatric patients, spinal cord injury with paraplegia
   - need a distended bladder

Question 11

MSU instructions

Answer 11

Female:
- spread labia + maintain separation
- cleanse periurethral area with moist gauze from back to front
- void initial 100-150 ml urine —> clean-catch 10-15 ml of urine

Male:
- retract foreskin, wash glans with soap + water
- void initial 100-150 ml urine —> clean-catch 10-15 ml of urine

Question 12

***Urinalysis

Answer 12

Gross + Microscopic examination of urine
1. Appearance

2. Chemical analysis
   - pH (normal: 5.5-6.5)
   —> overly alkaline (>7.5) suggest infection by an **urease-producing organism esp. in presence of stones (e.g. staghorn stones)
   —> **Proteus, **Klebsiella, **Pseudomonas etc.
   —> Urea converted by bacteria to NH3 —> ↑ pH —> facilitate precipitation of ***struvite calculi (alkaline) —> vicious cycle

• Osmolality
• SG (specific gravity)

3. Microscopic examination
   - RBC

• **WBC
  —> pyuria a good indicator of presence of clinical UTI
  —> absence of pyuria should raise suspicion of underlying UTI
  —> defined as **>2 WBC / HPF (or >10 WBC / ml)
  —> “sterile pyuria”: inflammatory conditions e.g. cancer, stones / TB
• Bacteria
  —> presence of bacteria **NOT equal to genuine bacteriuria
  —> bacteria only seen when **10^5 CFU/ml
  —> observed bacteria may be normal flora / contamination
• Other cells e.g. epithelial cells
  —> indicative of preputial / vaginal contamination (i.e. by skin epithelial cells)

4. Adjunctive tests
   - **Leukocyte esterase
   —> enzyme inside leukocyte (i.e. basically testing for presence of pyuria)
   —> test utilised in commercial dipstick
   —> LE +ve supports **pyuria
   —> sensitivity for underlying UTI 70-95%
   —> false negative: High SG, dehydration, glycosuria, urobilinogen in urine, excessive Vit C in urine, WBC lysis, neutropenia

• **Nitrites
  —> most **Gram -ve bacteria convert nitrates —> nitrites
  —> test utilised in commercial dipstick
  —> N +ve support **bacteriuria
  —> sensitivity for UTI 35-85% but specificity 92-100%
  —> false negative: **Pseudomonas, ***Gram +ve bacteria, Low SG

Question 13

Sterile pyuria

Answer 13

Pyuria without bacteriuria

DDx: (記: Stone, Malignancy, Infection)
1. **TB
2. **Bladder cancer (CIS)
3. **Urinary tract stones
4. Schistomsomiasis
5. Partially treated UTI
6. **Other inflammatory bladder conditions (e.g. interstitial cystitis, ketamine cystitis)

Question 14

Urine culture

Answer 14

“Significant” culture: **10^5 CFU/ml
- figure based on “asymptomatic” patients
- sensitivity ~50% for symptomatic UTI
- 20-40% of women clinical UTI present with only 10^2-4 CFU/ml
- **lower cut-off used for symptomatic UTI

Cut-off for significant culture:
- female uncomplicated cystitis: >10^3
- female uncomplicated pyelonephritis: >10^4
- female complicated UTI: >10^5
- male complicated UTI: >10^4
- **Suprapubic tap urine: **any growth

Question 15

Imaging

Answer 15

• Not required in most UTIs as **clinical + **urinalysis findings adequate for diagnosis
• Imaging in most women with UTI ***unremarkable + no additional useful information

Role in UTI:
1. Look for factors that require treatment ***beyond medical means
2. Diagnose a focus of bacterial persistence

(Indications in acute pyelonephritis (high fever, loin pain):
1. **Potential ureteral obstruction
2. **History of urolithiasis esp. infectious stones
3. Papillary necrosis
4. Poor response to medical treatment
5. **DM
6. **Polycystic kidney disease with poor renal function
7. ***Neuropathic bladder
8. Unusual uropathogen e.g. mycobacterium, fungus, urea-splitting organisms)

Question 16

***Terminology of UTI

Answer 16

1. Uncomplicated UTI
   - UTI in a host with structurally + functionally ***normal urinary tract
   —> indicate no ↑ risk of failing standard therapy
   —> e.g. acute cystitis in young sexually active females
2. Complicated UTI
   - UTI in structurally / functionally **abnormal urinary tract +/- **immunocompromised state
   —> indicate ↑ risk of failing standard therapy
   —> ↑ risk of progressing into sepsis / death

• e.g. UTI in presence of:
  —> **Indwelling catheter
  —> Recent hospitalisation
  —> **Neurogenic bladder
  —> **Bladder outlet obstruction
  —> **Vesicoureteric reflux
  —> Pregnancy / ***DM / immunocompromised state
  —> Multi-drug resistant organism

3. Isolated UTI
   - UTI isolated from last UTI ***>6 months
4. Recurrent UTI
   - UTI after resolution of previous one, at a frequency of **>=2 in 6 months / **>=3 in 12 months
   - documented by **negative culture in between episodes
   - 2 mechanisms
   —> bacterial **reinfection
   —> bacterial **persistence (same pool of bacteria)
   - 20% women with UTI will develop recurrence within 6 months
   - predisposition to recurrence is genetically determined (∵ mostly **reinfection rather than persistence)
   - important to document ***urine culture
   - need to sought out persistence + correct
5. Asymptomatic bacteriuria
   - defined as **>=10^5 CFU in female / **>=10^3 in men
   - presence of pyuria in absence of S/S does NOT equal to presence of clinical UTI
   - common in long-term catheters, institutionalised elderly, DM, female > male

Question 17

***Uncomplicated vs Complicated UTI

Answer 17

Uncomplicated UTI:
- Usual uropathogens (***E. coli 70-95%)
- Shorter duration of treatment
- Out-patient treatment
- Complete cure very likely

Complicated UTI:
- **Broader spectrum of bacteria (often drug-resistant)
- **Longer duration of treatment
- May require **in-patient treatment
- True cure without recurrence not possible unless **complicating features eradicated

Question 18

4. Recurrent UTI: Bacterial reinfection vs persistence

Answer 18

Reinfection:
- recurrent infection from a source **outside urinary tract
- caused by different / same organisms
- responsible for **>95% of recurrent UTIs in women
- due to underlying susceptibility to UTI (genetically determined easier adherence by bacteria)

Persistence:
- recurrent infection due to a **focus within UT
- caused by **same organism from same focus from same inoculum
- potentially correctable by removal of infective focus

Correctable bacterial persistence:
1. Infectious stones (**struvite)
2. **Infected atrophic kidney
3. ***Foreign body in UT
4. Urethral diverticulum
5. Medullary sponge kidney
6. Ureteral stump after nephrectomy
7. Infected urachal cyst
8. Papillary necrosis
9. Chronic bacterial prostatitis
10. Urinary fistula (e.g. colovesical fistula)

Question 19

***Risk factors for recurrent UTI

Answer 19

Pre-menopausal women:
- Sexual intercourse (frequency, new partner)
- *Use of spermicide + diaphragm
- Pelvic anatomy (urethra-to-anus distance)
- Age of first UTI
- Family history (genetic factors)
- *Prior antimicrobial use

Post-menopausal women:
- *Estrogen deficiency
- *Urinary incontinence
- *Presence of cystocele
- Large post-void residual urine
- History of UTI before menopause
- Genetic factors

*: correctable

Question 20

Management of recurrent UTI

Answer 20

General measures:
1. Avoid use of spermicide / diaphragm
2. *Observe personal hygiene
3. *Post-coital voiding
4. *Hydration to maintain adequate urine output
*: never shown to be associated with ↓ risk of recurrent UTI

Specific measures:
1. **Topical vaginal estrogen (level 1a evidence) —> make vagina acidic again
2. **Antimicrobial prophylaxis
- Post-coital prophylaxis (single dose after each intercourse)
- Self start “prophylaxis”
- Continuous prophylaxis

Question 21

5. Asymptomatic bacteriuria

Answer 21

• defined as >=10^5 CFU in female / >=10^3 in men
• presence of pyuria in absence of S/S does NOT equal to presence of clinical UTI
• common in long-term catheters, institutionalised elderly, DM, female > male

Screening / Treatment of asymptomatic bacteriuria is NOT indicated in:
1. Pre-menopausal non-pregnant women
2. Postmenopausal women
3. Men
4. Patients on indwelling catheters
5. Patients on nephrostomy tubes / ureteric stents
6. Patients with spinal cord injury

ONLY indicated in:
1. **Pregnant patients (∵ can lead to premature labour)
2. **Patients about to undergo **invasive genitourinary procedure (e.g. cystoscopy) for which there is risk of **mucosal bleeding

Question 22

Asymptomatic bacteriuria in Pregnancy

Answer 22

• Incidence of asymptomatic bacteriuria ~ to non-pregnant patients
• Physiological changes in pregnancy (**marked ↑ in GFR, **hydronephrosis, **hydroureter)
  —> progression from bacteriuria to **upper tract infection likely
• Upper tract infection during pregnancy associated with prematurity, LBW etc.
  —> **routine screening of urine + **treatment of bacteriuria is ***standard of care

Question 23

Asymptomatic bacteriuria in DM

Answer 23

• Very common in diabetic women
• prone to rapid progression of renal parenchyma infection if occurs
• screening + treating bacteriuria makes sense
  —> but studies show no ↓ in complications
  —> ∴ not clinically indicated to treat

Question 24

***Common UTI syndromes

Answer 24

Acute:
1. Cystitis (no fever, suprapubic pain, dysuria, haematuria)
2. Pyelonephritis (fever + **loin pain)
3. **Renal abscess / Pyonephrosis (if obstruction in ureter)
4. Prostatitis
5. Epididymo-orchitis
6. Urethritis / STD

Others:
1. Mycobacterial
2. Parasitic
3. Fungal

Question 25

Acute cystitis

Answer 25

Classic uncomplicated UTI
- usually young sexually active females

Causative organism:
- ***E. coli (most common)

S/S:
1. **Dysuria
2. **Frequency
3. **Urgency
4. **Haematuria
5. **Foul-smelling urine
6. No vaginal discharge
7. No systemic upset (∵ localised infection —> **no fever)

DDx:
- Other non-infective cystitis
- Vaginosis
- Herpes

Diagnosis:
- Clinical +/- Urinalysis
- ***NO need culture

Treatment:
- ***Empirical without further urine culture

Choice of antimicrobials:
- Likely microbiology
- Local antimicrobial resistance pattern
- Any recent antimicrobial use
- Costs, allergy, SE profile etc.

Management:
- **Single-dose treatment not recommended
- **3-day course of **Co-trimoxazole (Septrin) / **Fluoroquinolone (avoid Co-trimoxazole if resistance among E. coli >20%)
- Alternative: **Nitrofurantoin 7 day course (but high resistance among non-E. coli uropathogens)
- **Beta-lactams NOT recommended

(CHP: 1st line
- **Nitrofurantoin 50mg QDS 5-7 days
- **Augmentin 250mg TDS 5-7 days)

Question 26

Complicated cystitis

Answer 26

Potential complicating features:
1. ***Pregnancy
2. DM
3. Immunocompromised
4. Recent antimicrobial use
5. Recent urinary tract intervention
6. Nosocomial infection

Treatment:
- generally longer duration treatment required (>3 days vs uncomplicated)
- **10-14 days **Fluoroquinolones
- also measures to eradicate complicating feature

Question 27

Acute pyelonephritis

Answer 27

S/S:
1. **Fever
2. **Loin pain
3. Vomiting
4. Haematuria
5. Sepsis

• Potentially life-threatening
• **Imaging should be done (e.g. USG) to exclude underlying causes —> may have underlying obstruction accelerating disease tempo (e.g. **ureteral stones, strictures etc.) / ***abscess formation in kidney

Treatment:
- **10-14 days treatment
- **Fluoroquinolones + **3rd gen Cephalosporin
- Co-trimoxazole / Co-amoxiclav should **NOT be used empirically unless pathogen sensitivity known
- In areas with FQ-resistance / ESBL among E. coli >10%
—> **Aminoglycosides / **Carbapenems should be used

• If no improvement beyond ***72 hours —> CT contrast for renal abscesses / obstruction

Complications:
- ***Emphysematous pyelonephritis (fulminant form of pyelonephritis)

Question 28

Male UTI

Answer 28

• Much less common
• ~50% have ***underlying urologic abnormality (e.g. prostate obstruction, urethral stricture)
• Male UTI = complicated?

Investigate if:
1. Febrile UTI
2. Pyelonephritis
3. Recurrent UTI (chronic prostatitis)
4. History of voiding difficulty / AROU
5. Persistent microscopic haematuria
—> Investigate Lower UT to see for ***obstructions

Treatment:
- **7 day
- 2-6 weeks antibiotics if prostate involvement suspected —> **Quinolones preferred: excellent prostatic penetration

Question 29

Elderly UTI

Answer 29

Can cause mortality

Risk factors:
1. **Impaired elimination of urine (constipation, drug-induced ROU)
2. **Cystocele / **Prostate enlargement
3. Poorer perineal hygiene (e.g. fecal soiling)
4. **Neurologic impairment + poor mobility
5. ***Post-menopausal changes (lack of natural defence mechanisms against UTI)

S/S:
Non-specific symptoms
1. Decrease in general condition / delirium
2. Poor appetite
3. N+V
4. Diarrhoea
5. Fever
6. **Unexplained sepsis
7. **Hypotension / Shock (may be first presentation)

Treatment:
- 1 week for cystitis
- 2 weeks for pyelonephritis

Question 30

Genitourinary TB

Answer 30

TB urinary tract is **secondary infection from primary pulmonary TB
- reactivation of dormant focus
- **haematogenous
- only 1/4 patients have known history of TB
- symptoms usually arise ***10-15 years after primary infection
- 30-40% extrapulmonary TB (second only to lymphonodal TB)

Manifestations:
1. Kidneys
- abscess, fibrosis —> cicatrical complications
- **calcified, non-functioning kidney (*autonephrectomy)

2. Ureters
   - ***strictures
3. Bladder
   - ***cystitis
   - contracted “thimble” bladder
   - “golf-hole” ureteral orifice
4. Epididymis, Vas deferens
   - haematogenous spread
   - **abscess, sinus, beading of vas
   - infertility: **obstructive azoospermia
   - discharging sinus
5. Prostate
   - ***nodules
   - asymptomatic

S/S:
1. Chronic, non-specific
2. Frequency, dysuria, loin pain
3. Haematuria
4. Suprapubic pain, fever
(5. Scrotal sinus with discharge
6. Epididymal / prostatic nodules
7. Beading of vas)

Investigations:
- EMU x3 (Early morning urine)
—> **AFB smear
—> Culture (Lowenstein-Jensen medium 4-8 weeks / BACTEC 460 medium 2-3 days)
—> **PCR (only 6 hours)

Treatment:
- HERZ: Isoniazid + Ethambutol + Rifampicin + Pyrazinamide for 2 months
—> HR for 4-7 months
—> according to sensitivity