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UTI – definitions and pathophysiology

Urinary tract infection (UTI) – inflammatory response of the urothelium to bacterial invasion, associated with bacteriuria and pyuria

Bacteriuria – presence of bacteria in the urine

Cutoff for ‘significance’ is debated – initially thought to be 105 cfu / mL, but may be as low as 102 cfu / mL in symptomatic patients

Pyuria – presence of white blood cells in the urine, typically representing infection or inflammation

Bacteriuria without pyuria may represent colonisation

Sterile pyuria warrants further investigation if no known cause

Uncomplicated UTI – non pregnant women, with no known anatomical or functional urinary tract abnormality, without co-morbidities

Complicated UTI – all UTIs not fitting the above definition -> higher risk of complicated course

  • Men
  • Pregnant women
  • Underlying functional or anatomical abnormalities
  • Immunosuppression including diabetics

Normal host defences to urinary tract infection:

  • Antegrade flow of urine
  • Commensal flora of females – e.g. lactobacillus lowers vaginal pH
  • Oestrogen (reduces pH, maintains skin integrity)
  • Physical and chemical characteristics of urine (osmolality, pH, organic acid concentration, urea concentration)
  • Normal excretion/exfoliation of urothelial cells
  • Intact GAG layer
  • Tamm-Horsfall protein (binds E.coli, preventing adherence)

Pathogenicity: ability of an organism to cause disease  

Virulence: the degree of pathogenicity  

Virulence factors: factors which help bacteria avoid host defences, and assist in colonisation

Common organisms causing UTI:

  • E.coli – > 80 % of UTIs in some series – UPEC (uropathogenic E.coli) differentiated from normal gut colonisers
  • Klebsiella
  • Proteus
  • Enterococcus
  • Pseudomonas
  • Staph. Saprophyticus
  • Serratia

Pathogenic factors promoting infection / evading host response

  • Extracellular capsule – to avoid phagocytosis and reduce immunogenic response
  • Production of toxins and enzymes (gram negative sepsis commonly mediated by endotoxins)
  • Mechanisms to reduce efficacy of antibiotics
    • Intrinsic resistance – with these species selected for and replicated
    • Biofilms
    • Acquired – often plasmid mediated – e.g. production of beta-lactamase
  • Adhesion mechanisms to attach to the host
  • UPEC has a number of adhesins
    • Type 1 (mannose sensitive) pili
    • P pili (mannose resistant, p for pyelo)

Routes of infection:

  • Ascending
    • From bowel and skin -> ascend into bladder via urethra
    • Bladder -> kidney
  • Haematogenous
    • Uncommon – usually staph seeded
  • Lymphatic
    • Unusual and rare