Urinary Tract Infections

Question 1

Briefly describe the pathophysiology of urinary tract infections & name the likely causative microorganisms that can cause such infections.

Answer 1

1) Ascending route
- Colonic/fecal flora colonise periurethral area or urethra & ascend to bladder & kidney
- Higher risk in females > males due to shorter urethra, use of spermicides & diaphragms as contraceptives
- Usually by gram-negative GIT bacteria e.g. E. coli, Klebsiella, Proteus & Enterobacteriaceae
2) Descending route (rarer)
- Organism is likely found at distant primary site (e.g. heart valve [endocarditis], bone [osteomyelitis] -> bloodstream [bacteremia] -> urinary tract)
- Usually by gram-positive non-GIT microorganisms e.g. S. aureus & M. tuberculosis

Question 2

What are the normal host defence mechanisms that are important in the prevention of UTI?

Answer 2

1) Increased micturition w/ increased diuresis, so as to empty bacteria in bladder as urine
2) Antibacterial properties of urine & prostatic secretion
3) Anti-adherence mechanisms of bladder preventing bacterial attachment to bladder
4) Inflammatory response with polymononuclear leukocytes (PMN) which phagocytose bacteria to prevent/control spread

Question 3

What are some factors determining the development of UTI?

Answer 3

1) Competency of natural host defence mechanism
- Increased micturition & increased diuresis
- Antibacterial properties of urine & prostatic secretions
- Anti-adherence mechanisms of bladder
- Presence of polymononuclear (PMN) leukocytes
2) Size of inoculums
- Increased risk w/ urinary retention / obstruction
3) Virulence / pathogenicity of microorganisms
- e.g. bacteria w/ pili (E. coli) is resistant to washout or removal by anti-adherence mechanisms of bladder

Question 4

What are some host risk factors that increase the risk of developing UTI?

Answer 4

1) Females > males (shorter urethra)
2) Sexual intercourse & use of diaphragms / spermicides (increase colonisation at vaginal area & change in vaginal flora)
3) Structural abnormalities in urinary tract
- Prostatic hypertrophy
- Kidney stones
- Urethral strictures (narrowing of urethra)
- Vesicourectal reflex (backflow of urine from bladder to kidney due to valve malfunction)
4) Neurological dysfunction (e.g. stroke, diabetes, spinal cord injuries -> urinary retention)
5) Anticholinergics (results in urinary retention)
6) Catheterisation & other mechanical instrumentation
7) Diabetes (risk of neuropathy & high sugar content in urine promotes bacterial growth)
8) Pregnancy
9) Genetic association (esp. mothers & sisters)
10) Previous UTI

Question 5

What are some non-pharmacological counselling points that are recommended to minimise the risk of UTI?

Answer 5

1) Drink lots of fluid (6-8 glasses a day) to flush bacteria (watch for fluid restrictions)
2) Urinate frequently & go when you first feel the urge
3) Urinate shortly after sexual intercourse

For females specifically:

4) Wear cotton underwear & loose-fitting clothes to keep periurethra area dry
5) Wipe from front to back esp. after bowel movement
6) Modify birth control methods if having trouble w/ UTIs

Question 6

Briefly discuss how UTIs are classified.

Answer 6

1) Complicated UTIs
- Associated w/ conditions that increase potential for serious outcomes & risk of therapy failure
- i.e. UTIs in men, children & pregnant women or recurrent UTIs
- Urinalysis & urine culture are indicated
2) Uncomplicated UTIs
- Usually in healthy pre-menopausal, non-pregnant women of child-bearing potential w/ no Hx suggestive of abnormal urinary tract
- Urinalysis & urine culture not routinely indicated unless pyelonephritis

• Note that this is an overly simplistic classification!

Question 7

What are some factors that indicate that a UTI is likely to be a complicated one?

Answer 7

1) Males
2) Functional & structural abnormalities of urinary tract
3) Genitourinary instrumentation
4) Diabetes mellitus / immunocompromised hosts
5) Neurogenic bladder / renal insufficiency

Question 8

What are some clinical symptoms presented in a patient who has a likely lower UTI?

Answer 8

• Dysuria, urinary urgency / frequency, nocturia
• Suprapubic heaviness or pain
• Gross hematuria

Question 9

What are some clinical symptoms presented in a patient who has a likely upper UTI?

Answer 9

• Fever, rigour, chills & headache
• N/V & general GI symptoms
• Malaise
• Flank / abdominal pain
• Costovertebral tenderness (positive renal punch)
• Altered mental status, drowsiness & low alertness (esp. elderly pt.)
• Change in eating habits

Question 10

Besides examining for signs of UTI via vital signs, laboratory test results & radiological imaging, what other objective results can be used for the diagnosis of UTIs?

Answer 10

1) UFEME
- Pyuria if WBC > 10 per mm3; signifies presence of inflammation that may / may not be due to infection -> Absence of pyuria = unlikely UTI
- Hematuria if RBC > 5/HPF
- Gram staining results
- Presence of WBC casts indicates upper UTI (casts = mass of cells/proteins formed in renal tubules)
- High number of squamous epithelial cells suggests high levels of contamination
2) Nitrite test (e.g. of chemical urinalysis)
- Positive indicates presence of gram-negative bacteria
- Only GN bacteria can reduce nitrate to nitrite
- False-negatives can be attributed to inability to detect Gram-positives or P. aeruginosa (able to reduce nitrite into NO), low urinary pH or frequent voiding / dilution of urine
3) Leukocyte esterase (LE) test (e.g. of chemical urinalysis)
- Positive indicates leukocyte activities
- Correlates w/ significant pyuria (WBC > 10 per mm3)

Question 11

When is it necessary for pre-treatment cultures for a patient diagnosed with a likely UTI?

Answer 11

1) Pregnant women
2) Recurrent UTIs (relapse w/in 2 weeks or frequent)
3) Pyelonephritis
4) CA-UTI
5) UTI in men

Question 12

What is the most likely microorganism causing uncomplicated UTI?
Are there other possible microorganisms that can cause uncomplicated UTI?

Answer 12

Most likely (> 85%): Escherichia coli
Others include Staphylococcus saprophyticus (5-15%),  Enterococcus faecalis, Klebsiella pneumonia & Proteus spp.

Question 13

What is the most likely microorganism causing complicated UTI?
Are there other possible microorganisms that can cause complicated UTI?

Answer 13

Most likely (> 50%): Escherichia coli
Others include Enterococci, more resistant strains Enterobactericeae (Klebsiella spp., Proteus spp. & Enterobacter spp.) & Pseudomonas aeruginosa (healthcare-associated).

Question 14

What are possible risk factors that may result in complicated UTI caused by P. aeruginosa?

Answer 14

• Hospitalisation in the last 90 days
• Current hospitalisation >= 2 days
• Residence in nursing home
• Antimicrobial use in the last 90 days (consider ESBL resistance)
• Home infusion therapy
• Chronic dialysis

Question 15

What is a likely contaminant that may be found in urine culture?

Answer 15

Yeast (candida)

Question 16

If the urine culture results show that the infection is likely caused by Staphylococcus aureus, can we diagnose the current infection as an UTI?

Answer 16

No! Consider other primary sites of infection as S. aureus is commonly a result of bacteremia.

Question 17

It is generally recommended to treat patients displaying asymptomatic bacteriuria with a course of antibiotics. True or false?

Answer 17

False!
Only pregnant women & patients undergoing invasive urologic procedures with mucosal trauma a day later are treated with Abx despite being asymptomatic.

Question 18

Why is it recommended to treat pregnant women with asymptomatic bacteriuria?

Answer 18

Reduce development of pyelonephritis, risk of preterm (< 37 weeks) labour & low birth weight infants.

Question 19

Why is it recommended to treat patients undergoing invasive urologic procedures with mucosal trauma a day later with a course of antibiotics?

Answer 19

Prophylaxis to prevent post-operative bacteremia & sepsis.

To obtain urine culture first, then start Abx based on AST & culture results 12-24 h (1-2 doses) before the procedure.

Question 20

List all recommended first-line empiric Abx for the treatment of uncomplicated cystitis in women.

Answer 20

1) PO Nitrofurantoin 50mg QDS x 5 days

2) PO Cotrimoxazole 960mg BD x 3 days

Question 21

List all recommended first-line empiric Abx for the treatment of cystitis in pregnant women.

Answer 21

1) PO Cefuroxime 250mg BD x 7 days
2) PO Cephalexin 500mg BD x 7 days
3) PO Amoxicillin-clavulanate 625mg BD x 7 days

Question 22

What are some possible first-line empiric Abx for the treatment of uncomplicated cystitis in women with sulfa allergy?

Answer 22

1) PO Nitrofurantoin 50mg QDS x 5 days
2) PO Cefuroxime 250mg BD x 5 days
3) PO Cephalexin 500mg BD x 5 days
4) PO Amoxicillin-clavulanate 625mg BD x 5 days

Question 23

List all recommended first-line empiric Abx for the treatment of complicated cystitis in women.

Answer 23

1) PO Cotrimoxazole 960mg BD x 7 days
2) PO Nitrofurantoin 50mg QDS x 7-14 days
3) PO Fosfomycin 3g EOD x 3 doses

Question 24

List all possible empiric Abx for the treatment of community-acquired mild/moderate pyelonephritis in women.

Answer 24

First-line:
1) PO Ciprofloxacin 500mg BD x 7 days
2) PO Levofloxacin 750mg OD x 5 days
Alternatives:
3) PO Cotrimoxazole 960mg BD x 14 days
4) PO Cephalexin 500mg BD x 10-14 days
5) PO Amoxicillin-clavulanate 625mg TDS x 10-14 days

Question 25

List all recommended empiric Abx for the treatment of community-acquired severe pyelonephritis in women who require hospitalisation.

Answer 25

1) IV Ciprofloxacin 400mg BD
2) IV Cefazolin 1g q8h
3) IV Amoxicillin-clavulanate 1.2g q8h
4) Additional IV/IM Gentamicin 5 mg/kg to cover ESBL-producing E. coli / Klebsiella

Question 26

List all recommended first-line empiric Abx for the treatment of community-acquired UTI in men w/o concern for prostatitis.

Answer 26

Tx similar to complicated cystitis in women

1) PO Cotrimoxazole 960mg BD x 7 days
2) PO Fosfomycin 3g EOD x 3 doses

Question 27

List all recommended first-line empiric Abx for the treatment of community-acquired UTI in men with concern for prostatitis.

Answer 27

1) PO Ciprofloxacin 500mg BD x 10-14 days
2) PO Cotrimoxazole 960mg BD x 10-14 days
* Duration of Tx = 6 weeks if prostatitis is confirmed

If prostatitis is ruled out subsequently, possible to streamline ciprofloxacin to beta-lactams:

3) PO Cephalexin 500mg BD
4) PO Cefuroxime 250mg BD
5) PO Amoxicillin-clavulanate 625mg BD

Question 28

Define ‘nosocomial UTI’.

Answer 28

Onset of UTI > 48h post-admission

Question 29

Define ‘healthcare-associated UTI’.

Answer 29

UTI occurring in patients who have been hospitalised or underwent invasive urological procedures in the last 6 months or has indwelling urine catheter.

Question 30

List all recommended first-line empiric Abx for the treatment of nosocomial / healthcare-associated pyelonephritis.

Answer 30

Broad-spectrum beta-lactams used for empiric Tx.
Consider the possibility of P. aeruginosa & other resistant bacterias present.
1) IV Cefepime 2g q12h +- IV Amikacin 15mg/kg/day x 7-14 days
2) IV Imipenem 500mg q6h x 7-14 days
3) IV Meropenem 1g q8h x 7-14 days

For less sick patients:

1) PO Ciprofloxacin 500mg BD x 7-14 days
2) PO Levofloxacin 750mg OD x 7-14 days

• Shorter duration if no longer febrile in 3 days

Question 31

Define ‘catheter-associated UTI’.

Answer 31

Presence of symptoms or signs compatible with UTI w/ no other identifiable source of infection along with 10^3 cfu/mL of >= 1 bacterial species in a single catheter urine specimen in patients with indwelling urethral/suprapubic or intermittent catheterization (inserted for >= 48h), or in midstream voided urine specimen from patients whose catheter has been removed w/in previous 48h.

Question 32

What are some factors that increase the risk of developing CA-UTI?

Answer 32

1) Duration of catheterisation (most impt; 3-5% chance of isolating bacteria per day)
2) Colonisation of drainage bag, catheter & periurethral segment
3) Diabetes mellitus
4) Female
5) Renal function impairment
6) Poor quality of catheter care, including insertion

Question 33

If an indwelling catheter has been in place for _____ & still indicated, catheter should be replaced to hasten resolution of symptoms & reduce risk of subsequent CA-UTI bacteriuria & CA-UTI.

Answer 33

> 2 weeks at the onset of CA-UTI

Question 34

List all recommended first-line empiric Abx for the treatment of symptomatic CA-UTI.

Answer 34

1) IV Cefepime 2g q12h +- IV Amikacin 15mg/kg/day
2) IV Imipenem 500mg q6h
3) IV Meropenem 1g q8h
* 7 days Tx if afebrile in 3 days; otherwise 10-14 days Tx

For less sick patients:

1) PO/IV Levofloxacin 750mg OD x 5 days
2) PO Cotrimoxazole 960mg BD x 3 days (for women <= 65 y/o w/ CA-UTI w/o upper urinary tract symptoms after indwelling catheter has been removed)

Question 35

List all recommended first-line empiric Abx for the treatment of pyelonephritis in pregnant women.

Answer 35

1) PO Cefuroxime 250mg BD x 14 days
2) PO Cephalexin 500mg BD x 14 days
3) PO Amoxicillin-clavulanate 625mg BD x 14 days

Question 36

What are some non-pharmacological recommendations for the prevention of CA-UTI?

Answer 36

1) Avoid unnecessary catheter use (trial of catheter to see if pt. can urinate w/o help of catheter)
2) Use for minimal duration
3) Long-term indwelling catheters changed before blockage is likely to occur
4) Use of closed system (less fiddling of catheter & urine bag)
5) Ensure aseptic insertion technique
6) Topical/Prophylatic antiseptic & antibiotics not recommended
7) Chronic suppressive antibiotics not recommended

Question 37

What are some considerations when treating UTI in pregnant women?

Answer 37

1) Avoid fluoroquinolones
2) Avoid cotrimoxazole in first (neural tube defects in infants) & third (kernicterus) trimesters
3) Avoid nitrofurantoin at term (38-42 weeks)
4) Caution w/ aminoglycosides
5) Beta-lactams are first-line Abx
6) Duration of Tx = 7 days for asymptomatic bacteriuria & cystitis; 14 days for pyelonephritis

Question 38

What are some general patient counselling points for Abx?

Answer 38

• This is an antibiotic to treat your _____ infection.
• Take _ tablets/capsules _ times a day / about _ hours apart. Take ___ food. Do not take together with ___, space _ hours apart.
• Side effects may include…
• Complete the whole _ day course unless signs of allergy (like rash, itch, swollen eyes) or serious side effects occur.
• If allergy or any intolerable effects occur, stop taking and see your doctor immediately.
• You should feel better in 2-3 days, if not, please see your doctor.
• Do remember to complete the course even if you feel better.

Question 39

What are some adjunctive therapies for the management of UTI?

Answer 39

1) Pain & fever - paracetamol & NSAIDs
2) Vomiting - rehydration
3) Urinary symptoms - Phenazopyridine (Urogesic) 100-200mg TDS

Question 40

What are the therapeutic goals & monitoring parameters in the treatment of UTI?

Answer 40

1) Resolution of signs & symptoms
- Improvement/resolution in 24-72h after effective Abx initiation
- If fail to respond clinically w/in 2-3 days or have persistent positive blood cultures, consider further investigation to exclude bacterial resistance, possible obstruction, renal abscess or other disease processes.
2) Bacteriological clearance
- Repeat culture not required for pt. who responded
- Culture to document clearance of infection in pregnant women.
3) Absence of ADR & allergies