UTI

Question 1

definition

Answer 1

Urinary tract infection (UTI) refers to a symptomatic infection within the urinary tract.

Asymptomatic bacteriuria – significant numbers of bacteria in the urine but no symptoms of infection.
Currently – single species at > 100000 ml-1 from mid-stream urine sample.

Lower UTIs involve the bladder (cystitis) or urethra (urethritis).

Upper UTIs generally affect the kidneys (pyelonephritis) or ureters (ureteritis).

Question 2

prevelance

Answer 2

UTI is a very common bacterial infection, with approx. 1 – 3% of GP visits due to UTIs.

About 1 in 3 women will have had at least one UTI by age 24.

About 1 in 2 women will be treated for a symptomatic UTI.

Incidence of UTI in women increases with age.

Asymptomatic bacteriuria is more common in women than men.
In pregnancy – asymptomatic bacteriuria in range 2 – 10%, with incidence of acute cystitis being in the range 1 – 4%.

Question 3

more common in women

Answer 3

Anatomy – shorter urethra, closer to the bladder.

Birth control – use of spermicidal agents or diaphragms can increase risk of infection.

Menopause – decline in circulating oestrogen, causes changes to urinary tract, more vulnerable to infection.

Sexual activity – more common in sexually active women.

Question 4

single or recurrent

Answer 4

Single episode or recurrent. For recurrent UTIs, either a relapse by the same organisms or a reinfection with a different organism.

Question 5

complicated vs uncomplicated

Answer 5

Uncomplicated - individuals otherwise healthy, with no additional urinary tract problems

Complicated – associated with other factors including urinary obstruction, renal failure, urinary retention, presence of indwelling catheters, etc.

Question 6

risk factors

Answer 6

1. latrogenic/ drugs
2. behavioural
3. anatomic
4. genetic

Question 7

latrogenic drugs

Answer 7

1. indwelling catheter
2. antibiotic use
3. spermicides

Question 8

behavioural

Answer 8

1. voiding dysfunction
2. frequent sex

Question 9

anatomic

Answer 9

1. vesicoureteral reflux
2. female sex
3. pregnancy

Question 10

genetic

Answer 10

familial tendencies

Question 11

pathogenesis of UTI

Answer 11

1. acute kidney injury
2. pyelonephritis
3. ascension
4. uroepithelium penetration
5. colonisation

Question 12

tests

Answer 12

Generally rely on chemical tests (dipstick) and bacterial culture.
Definitions:
Dysuria – pain/discomfort on passing urine.
Polyuria – excessive urine production.
Pyuria – presence of pus/white blood cells (6 – 10 neutrophils per high magnification field of view from unspun, mid-stream urine).
Haematuria – blood in urine.
Suprapubic – relating to area above pubis.

Question 13

nitrites

Answer 13

test for asymptomatic infections caused by nitrate-reducing bacteria (including Gram negative uropathogens like E. coli, Enterobacter, Klebsiella, Citrobacter, Proteus)
BUT – not very sensitive
Negative in presence of non-nitrate reducing organisms
Nitrate-reducing bacteria need to be in contact with reagents for long enough to get visible reaction
Often bacteria are able to reduce nitrate to nitrogen, leading to false negative results

Question 14

leukocytes

Answer 14

can indicate an infection if present in high numbers (> 3 per microscopy field of view)
test detects leukocyte esterase
BUT – infections caused by trichomonas, chlamydia and yeasts can result in this without bacteriuria

Question 15

UPEC

Answer 15

Initial colonisation of GI tract, followed by colonisation of urethra into bladder.
Women 14 x more likely to suffer an ascending UTI than men.

environment can be hostile to e.coli

Virulence mechanisms fall into 3 categories:

1. Adhesion – prevent removal in flow of urine, there are fast flowing forces against side of the bladder
2. Survival – able to acquire iron and can evade host defences, low iron low nutrients environment
3. Toxicity – leads to inflamation.

Question 16

UPEC virulence

Answer 16

UPEC strains are opportunistic intracellular pathogens.

Essential to be able to bind and attach to host cells and tissues.

Primary adherence factors are pili and fimbriae.

Common adhesive organelles are type 1, P, S and FIC pili.

Type 1
Required for colonisation, invasion and persistence (bladder).

Have adhesin FimH:
Mannosylated uroplakins
Α3β1 integrins

Question 17

other virulence factors

Answer 17

1. Siderophores
   - bladder is an iron-limited environment
   - scavenge Fe3+
2. α-haemolysin (HylA)
   - secretes high concentration
   - causes pore formation in umbrella cells, promoting lysis and release of nutrients and iron
   - triggers exfoliation and highly expressed in IBCs
3. Cytotoxic necrotising factor 1 (CNF1)
   - affects actin modelling
   - causes membrane ruffling, aids internalisation

Question 18

pathogenesis during catheter

Answer 18

Proteus
Initial attachment due to expression of mannose-resistant Proteus-like (MR/P) pili.

Followed by production of urease which elevates pH.

EPS traps crystals – formation of crystalline biofilm.

If in contact with host tissues, toxins produced:
Haemolysin (HpmA) – inserts into cell membrane and induces pore formation.

Proteus toxic agglutinin (Pta) – punctures host membrane, cytosol leakage leads to osmotic stress and depolymerisation of actin filaments.

Question 19

antimicrobial resistance

Answer 19

In 2016 E. coli resistant to colistin was detected in a UTI sample from a woman in the US.

E. coli had the mcr-1 gene – confers protection against colistin.

Up to 8 million UTIs in US each year, at least 10% (increasing) are antibiotic resistant.