Urinary Tract Infections

Question 1

General definition of UTI’s

• general definition?
• Can be? ^v
• Infectious or not??
• Complicated or non-complicated?
• how many bacteria have to be present to be significant bacteria?

Answer 1

• Definition: Microbial colonisation of the urinary tract by pathogenic micro-organisms and infection of the structures of the UT together with signs and symptoms of inflammation.
• UTI’s can be ascending or descending
• Endogenous; non-communicable
• UTI’s can be both complicated or uncomplicated but uncomplicated can become complicated.
• Presence of at least 10^5 bacteria/ml of urine may be symptomatic or asymptomatic.

Question 2

• Cystitis: Lower UTI:
• Where does it take place?
• could it be ascending or descending?
• Common symptoms?
• Acute pyelonephritis (upper UTI):
• Where?
• ascending or descending?
• Symptoms?
• Recurrent UTI:
• can be?
• Relapse?
• Reinfection?

Answer 2

Cystitis:

• infection of the bladder, most common UTI.
• Generally ascending
• Common symptoms: syndrome of frequency, dsyuria and urgency, foul smelling/bloodstained urine.

Acute pyelonephritis:

• infection of one or both kidneys
• can be ascending (severe urinary reflux) complication of a UTI.
• Can be descending (hematological spread from distant infection)
• Symptoms: Back pain, chills, fever, frequency and dsyuria.

Recurrent UTI:
- May be relapse or reinfection

• Relapse: Recurrent UTI caused by the same organism that caused the original infection.
• reinfection: recurrent UTI caused by a different microorganisms.

Question 3

Microorganisms associated with UTI:

• Community UTI: name 4?
• Hospital UTI: name 8?

Other possible causes of UTI. (5)

Answer 3

Community UTI: Usually:

• E. coli 80%
• Staphylococcus 10%
• Saprophyticus 10%

Hospital UTI:

• E. coli 50%
• Proteus sp. Klebsiella sp. Enterobacter sp. 40%
• Staphylococcus aureus and (MRSA), Coagulase negative staphylococci, enterococcus faecalis, candida albicans 10%

Other causes:

• Viral, very rare. Cytomegalovirus
• Fungi; Candia albicans. (risk: Hospitalization, antibiotic use and catherization).
• Parasites. schistosome haematobium Fluke (middle east, africa, india).
• Mycobacterium tuberculosis/MAI (HIV, immunosuppression).

Question 4

Pathogenesis of UTI: E. coli virulence factors:
- E. coli serotypes that cause UTI’s:

• Attachment:
• Avoidance:
• Production of toxins:

Answer 4

• most common serotypes are O5, O17 and O25. (Uropathogenic E. coli UPEC) Serotypes are determined on the O (polysaccharide), F (fimbriae), K (capsular polysaccharides) antigens, H (flagellum).
• Attachment: Fimbriae: 100-400 per bacterium
  
  • P-fimbriae (Pyelonephritis Associated Pili) - binds
    to galactose disaccharide moieties on p blood
    group antigens of RBC or epithelial cells of the
    urinary tract.
  • Type 1 fimbriae - binds mannose receptor.
    (secondary binding) The receptor is found in UT.
• Avoidance of the host defence:
  
  • polysaccharide capsule, K1 (Sialic acid) this mimics
    host sialic acid.
• Production of exocellular factors:
  
  • Haemolysin
  • siderophores (enterobactin, aerobactin).

Question 5

Treatment:

• Symptomatic?
• Bacteriuria (symptomatic or asymptomatic)?
• Sample?
• Collection of sample?

Answer 5

• ANY Symptomatic UTI requires antibiotics.
• Bacteriuria (symptomatic or asymptomatic) in preschool children with vesicoureteral reflux and pregnant women require antibiotics.
• Urine sample for microbiological analysis should always be taken prior to treatment.
• Collection of sample could be a mid stream urine (most common), bag urine/suprapubic aspiration, catheter specimen of urine (CSU).

Question 6

Treatment of UTI:

• Uncomplicated UTI (short course therapy)
  - Nitrofurantoin: mode of action?
  - Trimethoprim: mode of action?

Complicated upper UTI (pyelonephritis):

 - Ciprofloxacin: MOA?
 - Ceftriaxone: MOA?

Answer 6

Uncomplicated:
- Nitrofurantoin: QTS. Reduced by bacteria flavoproteins
(nitrofuran reductase): Ribosomal protein & DNA damage: cellular respiration: pyruvate metabolism.
- Multitarget activity may account for current widespread
sensitivity.
- Can be given in pregnancy.

Trimethoprim: BD

• MOA: inhibits dihydrofolate reductase (DHF) cannot be reduced to THF stopping thymidine synthesis thus DNA production inhibited.
• Cannot be given in pregnancy.

Complicated:

• Ciprofloxacin: BD or IV
• Inhibition of DNA gyrase
• huge tissue concentrations achieved
• avoid in pregnancy
• Ceftriaxone: IV only once daily:
• Inhibits Penicillin-Binding-Protein.
• can cause hypersensitivity.

Question 7

Prevention of UTI: (5)

Answer 7

• Low dose antibiotics
• Cleanse genitals before sex and after.
• Single dose antibiotics after sex
• drink plenty of water/do not resist urination
• Cranberry juice: condensed tannins.

Question 8

Diagnostics:

• request
• Collection
• Transport
• Non-culture techniques
• Culture techniques
• Identification

Answer 8

• Request form : full completed
• Sample: Mid stream urine red top boric acid
• transport: <24hrs boric acid refrigeration.
• Non-culture:
  - Microscopy: Allows rapid preliminary report.
  - Examine for bacteria, WBC, RBC, parasites
  - Presence of WBC and high number of
  bacteria is suggestive of UTI.
  - Presence of RBC may indicate other diseases
  e.g renal tuberculosis/carcinoma
• Culture: - Semi quantitate culture:
  - 2uL of MSU culture onto CLED agar (cystine
  lactose electrolyte deficient agar)
  - 37 degrees
  - 20-200 colonies on CLED = 10^4/10^5
  CFU/ml.
  - >200 + colonies = 10^5 CFU/mL
  - E. coli is a lactose fermenting colony so turns
  yellow on CLED.
• Identification:
  - Basic ID is often sufficient.
  - Full ID: analytical profile index - test
  commonly positive for E. coli = Indole,
  LDC/ODC, fermentation of glucose, sorbitol,
  mannitol.
  - test commonly negative: Urease, Citrate,
  gelatin.

Question 9

Sterile pyuria:

- If WBC present on microscopy but no bacteria recovered from culture on CLED agar (causes) (4)

Answer 9

• Renal tuberculosis
• Antibiotic treatment prior to MSU.
• Urethritis (e.g STI’s: Trichomonas vaginalis, Chlamydia trachomatis).
• Vaginitis - vaginal discharge.