T3 L14: Urinary tract infections

• How is the epidemiology of UTIs?

  common: 2nd only to resp infections; 1-3% of all GP consultations

  Significant cause of morbidity in females of all ages, infant boys and older men

  20% elderly have asymptomatic bacteriuria.
• What are the consequences / sequelae of UTIs?

  Societal and individual costs – health care costs (GP, ED and hospital), time missed from work

  Frequent recurrences

  Uncontrolled infection / sepsis

  Renal damage in young children

  Preterm birth

  Recurrent courses of antibiotics contribute to antimicrobial resistance and risk of CDI (C. difficile infection)
• What are the different classifications of UTIs?

  Uncomplicated “Lower” UTI:

  • Cystitis
  • Urethritis, prostatitis, epididymo-orchitis

  Uncomplicated “Upper” UTI:

  • Acute pyelonephritis
• What does 'uncomplicated' mean in relation to UTIs?

  no anatomical or neurological abnormalities of the urinary tract
• What is the aetiology of UTIs?

  Mainly: E. coli (UPEC - Uropathogenic E. coli)

  Uncomplicated UTI:

  • bacteria bind directly to the bladder epithelium, the umbrella cells (also known as superficial facet cells), intermediate cells and basal cells

  Complicated UTI:

  • bacteria bind to a urinary catheter, a kidney stone or a bladder stone, or when they are retained in the urinary tract by a physical obstruction.

  
• Most UTIs = gut bacteria ascending urethra, so women more susceptible than men
• What three factors does bacterial virulence depend on?

  Adhesion, invasion, evasion
• How does Adherence occur in UTIs?

  E coli express:

  • Type 1 pili: colonisation, invasion, persistence
  • P-pili: confer tropism to kidney
• How does Invasion occur in UTIs?

  Type 1 pilus → binds host cell → induce actin rearrangement → cause uptake of bacteria → intracellular protection (from antibiotics)

  
• What is the host cell defence against bacteria invasion?

  TLR4 recognises LPS and triggers exoctyosis
• How does evasion occur in UTIs?

  UPEC escapes TLR4 by:

  escape into cytoplasm → multiples into 'intracellular bacterial communities' (IBC). Then:

  • go on to invade other cells
  • invade transitional cells below to establish 'quiescent intracellular reservoir'
• How does UPEC survive in the bladder?

  adaptations to enable nutrient acquisition:

  • Secrete Haemolysin A: forms pores → cell lysis
  • Secrete Siderophores: scavenge iron
  • Adopt Filamentous morphology: harder for neutrophils to kill them

  
• E. coli strains originate from a reservoir in the gastrointestinal flora with the hypothesis of a faecal–vaginal–periurethral route of infection.
• How does the pathogenesis of UPEC go?

  1. contamination of periurethral area with uropathogens from gut
  2. colonisation of urethra & migration into bladder
  3. colonisation and invasion of bladder (mediated by pili & adhesins)
  4. neutrophil infiltration
  5. bacterial multiplication & immune system subversion
  6. Biofilm formation (behaviour to act as multicellular to survive)
  7. epithelial damage by bacterial toxins and proteases
  8. ascension to kidneys
  9. colonisation of kidneys
  10. host tissue damage by bacterial toxins
  11. bacteraemia (bacteria in blood)
• What are the host factors of lower UTI?


  • Obstruction (prostatic hypertrophy, urethral valves or stricture)
  • Poor bladder emptying   (neuropathic (MS, spinal cord injury), bladder diverticula, pelvic floor disorders)
  • Catheterisation/instrumentation
  • Vesico-enteric fistula
  • Sex  (female – vaginal or anal; male – insertive anal)
  • Diabetes
  • Genetics: non-secretors of ABH blood group antigens, esp in premenopausal women; and variable expression of the CXCR1 receptor, involved in neutrophil activation
• What are host factors of upper UTI?

  • May follow on from lower UTI
  • Vesico-ureteric reflux (urine flows back from bladder into ureters)
  • Obstruction (eg calculus, stricture)
• How are UTIs diagnosed?

  • Clinical symptoms
  • Urine dipstick testing
  • Urine culture
• What are the symptoms of Cystitis?

  • cystitis: inflammation of bladder
  • bladder and urethral symptoms
  • overlap with urethritis
  • dysuria (burning while urinating), frequency, urgency, suprapubic pain
  • nocturia (waking up in the night to go pee)
  • cloudy urine / visible blood

  Children, elderly and catheterised can be non-specific, such as delirium, lethargy so consider the diagnosis among other causes.
• What are the symptoms of Pyelonephritis?

  Pyelonephritis - kidney infection

  • fever, rigors, loin pain
  • renal angle tenderness
  • often lower UTI symptoms in addition
  • if pain radiation to groin, suspect stone
  • risk of bacteraemia
• What is urine dipstick used for as a form of urinalysis?

  has value to rule out, rather than rule in, UTI in patients with lower pretest probably of UTI

  main use to determine treatment if symptoms are vague:

  • Not diagnostic on their own
  • Not useful if >65y or if catheterised
• What does the urine dipstick test for?

  • Look for nitrites, leucocytes and red blood cells (RBC)
  • Leukocyte esterase: is an enzyme released by inflammatory cells such as neutrophils and macrophages, and a positive test reflects an increased presence in the urinary tract.
  • Nitrate reductase: enzyme produced by Gram negative bacteria to reduce nitrates to nitrites

  
• What are the NICE guidelines for female <65 UTIs?

  68% with 1 of the 3 key diagnostic characteristics will have a culture-confirmed UTI. 

  Use the dipstick to increase diagnostic certainty and reduce unnecessary antibiotics
• What are the principles of a urine culture?

  • Urine in the bladder should be sterile in the absence of a UTI
  • However, it can be contaminated by bacteria colonising the distal urethra, or hands/genital contamination.
  • A mid-stream urine (MSU) reduces the effects of urethral contamination by avoiding the initial and end stages of micturition.  The initial urine flow washes away urethral colonisers.
• What are the types of urine specimens?

  Midstream urine

  Suprapubic aspirate

  Catheter urine:

  • acute
  • intermittent self catheterisation
  • indwelling

  Not recommended: clean catch urine, bag urine, pad urine
• What are the stages of collecting an MSU (mid stream urine) sample to diagnose bladder or urinary tract infections?

  1. Wash hands
  2. Open container - do not touch inside
  3. Wipe / wash before passing urine
  4. Pass urine into toilet for 3 seconds, then stop
  5. Collect the next 10-20mL, then pass the rest into toilet
  6. Replace lid
  7. wash hands
  8. take sample to doctor or nurse

  
• Why is Boric acid used for midstream urine samples?

  helps to maintain microbiological quality of specimen

  prevents cell degradation and overgrowth of organisms that can occur if sample is not analysed within 4 hours of collection

  however; can cause false negative if urine not filled to correct mark

  
• What laboratory diagnostic techniques are done on the MSU sample?

  • Microscopy (unless imunosuppressed or neonate): automated scan for red and white cells, organisms and epithelial cells
  • Culture and antibiotic sensitivity: quantitative (how many bacteria in that sample) 'significant bacteria'
• What should be considered in antibiotic treatment?

  empiric treatment, so need to consider:

  • target organisms
  • route of administration
  • target site
  • side effects
  • resistance (known or likely)
• What is important about antibiotic resistance?

  Changes over time

  Varies geographically

  Main risk factor for resistant E coli in community is previous antibiotic treatment

  
• How do we know about antimicrobial resistance (AMR) rates?

  report routine antimicrobial susceptibility testing (AST) results to PHE national laboratory surveillance system

  used to inform antibiotic prescribing guidance

  however, may be biased, so:

  key recommendation is sentinel surveillance: base resistance estimates on AST data collected from wider range of patients
• How are UTIs prevented?

  Correct any underlying host causes

  Antibiotic prophylaxis

  Behavioural changes eg high fluid intake, void after sex, double void
• What is Catheter-associated UTI?

  Bacteria colonise the catheter and bladder at a rate of 3-5% people / catheter day

  • Removal of catheter will clear bacteria in most cases
  • Usually asymptomatic, but some will develop UTI, and bacteremia, sepsis and death may result.
  • 21% of patients with an E coli bloodstream infection had UC inserted/ removed/ manipulated in prior 7days
• How are the key interventions regarding the prevention of catheter-associated UTIs?


  Use only for good reason:

  • measurement of urine output in acutely unwell
  • mx of acute retention / obstruction
  • selected surgical procedures

  Aseptic insertion

  Closed drainage system

  Daily review of need: remove promptly when no longer indicated

  Consider alternatives

  
• How do we diagnose a CAUTI?

  CAUTI: catheter-associated UTIs

  Assess for clinical signs and symptoms

  Take catheter sample of urine

  Dip stick testing must NOT be used because it will be positive.
• What is Asymptomatic baceriuria?

  the presence of bacteria in the properly collected urine of a patient that has no signs or symptoms of a urinary tract infection

  Best left untreated unless pregnant

  Extremely common in elderly patients: organisms often lack virulence factors

  Treatment is not benign - adverse effects, financial costs, development of resistant strains, risk of C. difficile infection
• What is the difference between relapse vs recurrence?

  Relapse: same uropathogen causes UTI symptoms within 2 weeks of completing appropriate AB treatment

  Recurrence: at least 2 culture-proven episodes in 6 months, or at least 3 in 1 year

  • beyond initial 2 weeks
  • or a different uropathogen