Urinary Tract Infection
What is the pathogenesis
associated with UTI?
1 Ascending (most common route of infection)
- Colonic/faecal flora colonise peri-urethral/ urethra ascend to bladder and kidney
- Higher risk in females (shorter urethra) and in use of contraceptives i.e. spermicides and diaphragms (disrupts
natural ecologic of urinary tract)
- E Coli, Klebsiella, Proteus
2 Haematogenous/ descending
- Organism at distant primary site (e.g. heart valve, bone) enters blood i.e. bacteraemia kidney kidney
abscess
- Staphylococcus aureus, Mycobacterium tuberculosis
How can we classify UTI?
1 Complicated UTI
o Associated with potential for (1) serious outcomes, (2) risk for therapy failure or, (3) recurrence
o Infections in men, children, pregnant women
o Presence of complicating factors:
- Functional and structural abnormalities
- Genitourinary instrumentation
- Diabetes mellitus
- Immunocompromised
- Resistant organisms
2 Uncomplicated
o In females of childbearing age who are otherwise healthy, with a normal urinary tract
What are the factors
determining the
development of UTI?
1 Competency of natural host defence mechanisms
2 Size of inoculum
Increases with obstruction or urinary retention bladder unable to purge bacteria
3 Virulence/ pathogenicity of microorganism
Bacteria with pili e.g. E. Coli are resistant to washout or removal by anti-adherence mechanisms of bladder
more likely to cling onto mucosa to cause infection
How does natural host
defense mechanism
prevent UTI?
To prevent microorganism invasion,
o Bacteria in bladder stimulates micturition with increased diuresis emptying of bladder and because urine
has high organic acid, extreme osmolality and high urea making it difficult for bacteria to grow
o Urine and prostate secretions have antibacterial properties
o Anti-adherence mechanism of bladder
If microorganism has invaded,
o Inflammatory response with polymorphonuclear leukocytes phagocytosis prevent/control spread
What are the risk factors of
UTI?
What are the anatomical,
hormonal and physiological
changes to urinary tract
that predisposes pregnant
women to UTI?
What are the organisms
most commonly isolated in
UTI?
Females > males because females have shorter urethras and lack prostate secretions
Structural abnormalities e.g. prostatic hypertrophy, urethral strictures, tumours causes urinary retention
unable to purge bacteria size of inoculum
(3) Neurologic malfunctions e.g. stroke, diabetes, spinal cord, injuries bladder cannot be cleared
(4) Vesicoureteral reflux i.e. urine is forced back up through the ureter to kidney risk of pyelonephritis
(5) Anti-cholinergic drugs urinary retention
(6) Catheterization and other mechanical instrumentation introduces bacteria into urinary track + patients
who are catherized already have urological problems predisposed to UTI
(7) Diabetes urine with sugar encourages microbial growth
(8) Pregnancy
(9) Sexual intercourse introduces bacteria
(10) Use of diaphragms and spermicides alter flora pathogenic microbial growth
(11) Genetic association (positive family history)
(1)
(2)
o Increased smooth muscle relaxation
o Dilatation of renal pelvis and ureters
Facilitates entry of bacteria into bladder
o Increase in bladder capacity
o Decreased ureteral peristalsis
o Partial obstruction of ureter due to enlarging fetus
Causes urinary retention microbial load
o Estrogen may facilitate infection of upper urinary tract by UTI
o Pregnancy associated glycosuria and aminoaciduria provides good medium growth for bacteria
Note: urinary tract returns to normal by approximately 2 months post partum
Un-complicated or community-acquired infections:
o E. Coli (85%)
o Staphylococcus saprophyticus (5-15%)
o Enterococcus faecalis, Klebsiella pneumoniae, Proteus spp
Complicated or nosocomial infections:
o E. Coli (50%)
o Enterococci
o Proteus spp, Klebsiella spp, Enterobacter spp
o Pseudomonas aeruginosa
Others:
o Staphylococcus aureus commonly due to bacteremia consider kidney abscess
o Staphlococcus epidermis skin commensal generally considered a contaminant consider other
sites of infection
o Candida spp common in gut possibly contaminant consider other sites of infection but candida is also
What is the typical clinical
presentation of UTI?
What are the tests used to
support diagnosis of UTI?
commonly seen in critically ill or chronically catherised patients
Lower urinary tract infection symptoms usually local urinary symptoms
o Dysuria
o Urination urgency and frequency
o Nocturia i.e. frequent urination at night
o Suprapubic heaviness or pain
o Gross hematuria
Upper urinary tract infection systems usually systemic symptoms
o Fever and headache
o Nausea, vomiting, flank or abdominal pain
o Malaise and rigors
o Costovertebral tenderness i.e. positive renal punch whereby doctor pressed against where kidneys are
located and patient reports pain
To confirm presence of infection, urine is collected and sent for urinalysis and culture
Urine is collected via:
1 Mid-stream clean-catch
2 Catheterisation i.e. where a new catheter is placed in bladder to collect urine
3 Suprapubic bladder aspiration i.e. where a needle is inserted into bladder to aspirate directly
Microscopic urinalysis/ UFEME
o WBC
- > 10 WBC/mm3 = pyuria
- Signifies presence of inflammation, may or may not be infection
- In a symptomatic patient, pyuria correlates with significant bacteruria
- Absence of pyuria = unlikely UTI high negative predictive value
o RBC
- Presence (microscopic > 5 HPF or gross) = hematuria
- Frequently occurs in UTI but not specific
o Microorganisms identify bacteria or yeast via Gram stain
o WBC casts i.e. masses of cells and proteins that form in renal tubules (kidneys)
- Indicate upper urinary tract infection
Note: presence of squamous epithelial (source: from other urethra) suggests contamination
Chemical urinalysis/ dipstick
o Nitrite
- Positive test = presence of gram-negative bacteria because only gram-ve bacteria can reduce nitrates to
nitrites
- Requires at least 105 bacteria/mL
- False negative results from: gram-+ve bacteria and P. aeruginosa, low urinary pH, frequent voiding, dilute
dilute urine
o Leukocyte esterase
- Positive test detects esterase activity of leukocytes in urine
- Corelates with significant pyuria (> 10 WBC/mm3)
Is it necessary to obtain
urine culture for every
patient?
Is there a need to treat
every positive urine
culture?
Urine Culture GOLD STANDARD
Definition of significant bacteruria are as follows:
Asymptomatic female
> 105 CFU/mL x 2 readings
Asymptomatic male
> 105 CFU/mL x 1 reading
Symptomatic (male or female)
> 103 CFU/mL
From urinary catheter (male or female)
> 102 CFU/mL
From suprapubic catheter (male or female) ANY growth in a symptomatic patient
It is NOT necessary in young women with uncomplicated cystitis because presence of urinary symptoms w/o
vaginal discharge correlates with 90% positive predictive for acute cystitis and abx can be given based on
susceptibility patterns and UTI will respond to treatment
However, pre-treatment cultures may be necessary for
o Pregnant women
o Recurrent UTI (relapse within 2 weeks or frequent)
o Pyelonephritis
o Catheter-associated UTI
o All men with UTI
Only treat positive urine culture if the patient is symptomatic
Do not treat if patient is asymptomatic UNLESS:
o Preschool children (especially < 5y/o)
- Because children amy not be able to verbalise symptoms
- Treat based on culture and sensitivity, not empirical
o Pregnant
o Patients undergoing invasive urologic procedures e.g. transurethral resection of prostate (TURP or cystoscopy
with biopsy
- Because there is a chance that mucosa of urinary tract may be perforated during the procedure
introducing bacteria into the blood causing bacteremia
- give prophylaxis abx
- Obtain cultures then start abx bassed on culture and sensitivity 12-24h before procedure
- Continue until urine catheter is out
What are the goals and
monitoring of therapeutic
responses?
What are recurrent UTI
infecctions?
1 Resolution of signs and symptoms after 24-72h of abx initation
- If the patient fails to respond within 24-72h or has persistently positive blood or urine cultures, investigate for
(1) bacterial resistance, (2) possible obstruction, (3) renal abscess
2 Bacteriological clearance
- Repeat urine culture for pregnant women to document clearance of infection
- Repeat culture is not requires for other patients who have responded
There are 2 types of recurrent infections.
How do we manage
recurrent UTI infections?
Apart from antibiotics, what
are the adjuctive therapies
for UTI?
What are the non-anti
microbial options for
prevention?
What are the nonpharmacological advice for
patients?
What are the special
populations of UTI patients
which we would be
concerned with?
Why is it important to treat
asymptomatic bacteruria in
pregnant women?
When do we screen
pregnant women for
bacteriuria?
What are the
considerations in antibiotic
1 Relapses (20%) persistence of infections of the same organism (usually within 2 weeks)
o Indicates that patient may have renal involvement, structural abnormalities or chronic bacterial prostatitis
o Re-treat with prolonged duration of abx for 2-6 weeks
2 Reinfections (80%) infection with different organism or after 2 weeks of prior UTI episode
o Treat as per separate infections
o But note for risk factors and counsel patient accordingly to modify lifestyle
1 Infrequent recurrence (< 3 infections/ year)
o Treat each episode as a separate infection
2 Frequent recurrence (> 2 infections in 6 months or > 3 in 1 year)
o Need to evaluate reason for recurrence e.g. structural or neurogenic abnormalities
o Prophylaxis
- Not recommended because it tends to exert selection pressure on more pathogenic bacteria
- Treat underlying infection before starting long-term prophylaxis
- Usually give 3-12 months then reassess
o Post coital prophylaxis
- Single dose after sexual intercourse
o Intermittent self-treatment
- Patient starts course of therapy with onset of typical signs and symptoms of cystitis
- Women with recurrence are > 90% accurate in identifying a new episode
- Suitable for women who may develop infection while travelling or otherwise unable to access healthcare
- Regimen as per acute uncomplicated cystitis
For pain and fever Paracetamol or NSAIDs
For vomiting counsel to drink more water + oral rehydration salts
For urinary symptoms:
o Phenazopyridine (Urogesic)
- Exerts topical analgesic effect on urinary tract mucosa symptomatic relief
- Treatment should be limited to duration of symptoms
- Do not use in G6PD
- ADR: nausea, vomiting, orange-red discolouration of urine and stool
o Urine alkalinisation
- Relieves discomfort in mild UTI but no proven benefit
1 Cranberry juice (active ingredient: cranberry proanthocyanidine)
- Inhibits adherence of E. Coli to urinary tract epithelial cells
2 Intravaginal estrogen cream
- Decreases UTI incidence in post-menopausal women by restoring vaginal flora, preventing colonization by E.
Coli
3 Lactobacillus probiotics
- Works by restoring normal vaginal flora ans has a protective effect against E. Coli colonisatiion
Drink 6-8 glasses of water a day to flush the bacteria. But do not drink this much if patient has kidney failure.
Urinate frequently as bacteria can grow when urine stays in the bladder for too long
Urinate shortly after sex to flush away bacteria which may have entered urethra during sex
Wipe from front to back especially after bowel movement
Wear cotton underwear and loose-fitting clothes so that air can keep the area dry. Avoid tight-fitting jeans and
nylon underwear, which trap moisture and can help bacteria grow.
o For women using spermicide or diaphragm for birth control, consider alternative contraceptives. Also,
unlubricated condoms or spermicidal condoms increase irritation, which may help bacterial grow.
o
o
o
o
o
UTI in pregnancy and catheter-associated UTI
Recall: usually, we only treat a positive urine culture IF the patient is symptomatic but pregnant women is one of
the exceptions. This is because if left untreated,
o More likely to develop symptomatic UTI later in pregnancy
o Post-partum UTI is more common in women with bacteruria during pregnancy
o Development of pyelonephritis in 20-50%
o Increases risk of preterm delivery, low birth weight infant and perinatal mortality
We cannot rely on symptoms to indicate UTI
o Obtain urine culture or 12-16 weeks gestation or first prenatal visit
o If negative next urine culture at 3rd trimester
o If positive must treat and monitor for bacteriuria at every monthly visit until delivery
choice for pregnant
women?
What is the antibiotic
regime duration for
pregnant women?
What monitoring do we do
for UTI in pregnant
women?
o Avoid ciprofloxacin because of fetal cartilage damage
o Avoid co-trimoxazole in 1st and 3rd trimester
- In 1st trimester, folate antagonism may cause neural tube defects
- In 3rd trimester, sulphonamides displaces bilirubin from albumin kernicterus (hyperbilirubinemia)
- Also, concern for fetus being g6pd deficient
o Nitrofurantoin avoided at term (38-42 weeks) because conern for fetus being g6pd deficient
o Aminoglycosides are used with caution due to fetal 8th cranial nerve toixicty with older AG e.g. kanamycin and
streptomycin
o Beta-lactams are safe options 1st choice in pregnancy
7 days for asymptomatic bacteruria or 14 days for cystitis
14 days for pyelonephritis
What is catheterassociated UTI?
What are the risk factors
for catheter-associated
UTI?
What are the causative
organisms of catheterassociated UTI?
What are the treatment
considerations for catheterassociated UTI?
o Follow-up urine culture 7 days after completion of therapy must be done to ensure that bacteria is eradicated
o If negative surveillance cultures every month until after delivery
o If persistent or recurrent bacteruria,
- Treat again with 7-14 days regimen
- Consider prophylaxis until delivery
- Follow-up urine culture after delivery
- Evaluation of urinary tract for anatomic or physiologic abnormalities 3-6 months postpartum
Catheter-associated UTI is:
- Presence of symptoms or signs compatible with UTI with no other identified source of infection AND
- 102 cfu/mL of > 1 bacterial species in
- Either a single catheter urine specimen in patients with (1) indwelling urethral, indwelling suprapubic or
intermitten catheterization or
- Mid-stream voided urine specimen from a patient whose catheter has been removed within the previous 48h
Note: symptomtic manifestations are uncommon i.e. < 10% fever cases are due to UTI and not usually associated
with excess mortality
1 Duration of catheterization (MOST IMPT FACTOR)
2 Colonisation of drainage bag, catheter and periurethral segment
3 Diabetes
4 Female
5 Renal function impairment
6 Poor quality of catheter care, including insertion
Short-term catheterization (< 7 days) 85% single organisms reflecting those that prevail in environment e.g. E.
Coli, Klebsiella
Long-term catheterization (> 28 days) 95% are polymicrobial (2-3 organisms) and there is a need to consider
Pseudomonas aeruginosa
How to prevent catheterassociated UTI?
o Treatment fo asymptomatic bacteruria is not recommended except prior to traumatic urologic procedure (refer
above) only give antibiotics if symptomatic CA-UTI
o Removal of catheter should always be considered
o If indwelling catheter has been placed for > 2 weeks at the onset of CA-UTI and is still indicated, the catheter
should be replaced to hasten resolution of smx and reduced risk of subsequent CA-bacteruria and CA-UTI
o Symptoms include: new onset or wosening of fever, rigors, altered mental state, malaise, lethargy with no other
identifiable cause
o Flank pain, costovertebral angle tenderness, acute hematuria, pelvic discomfort
o If patient is stable and fever is low grade can consider observation over immediate abx
o Urine (+/-) blood culture must be taken before abx is given
1 Avoid unnecessary catheter use and use for minimal duration
2 Change long-term indwelling catheters before blockage is likely to occur
3 Use closed systems lesser manipulation required lesser contamination
4 Ensure aseptic insertion technique
5 Topical antiseptic of antibiotics not recommended
6 Prophylactic antibiotics or antiseptics not recommended
7 Chronic suppressive antibiotics not recommended
Acute
uncomplicated
cysitis in
women
Treatment
1st line:
PO co-trimoxazole 800/160mg BD x 3/7
PO nitrofurantoin 50mg QDS x 5/7
Alternative:
PO fosfomycin trometamol 3gm single dose
PO fluoroquinolones x 3/7:
PO ciprofloxacin 250mg BD
PO levofloxacin 250mg OD
PO ofloxacin 200mg BD
PO beta-lactams x 3-7/7:
PO cefuroxime 250mg BD
PO cephalexin 500mg BD
PO augmentin 625mg BD
Community
acquired
pyelonephritis
For complicated cystitis: treat for longer duration i.e.
7-10 days
1st line:
PO fluoroquinolone
PO ciprofloxacin 500mg BD x 7/7
PO levofloxacin 750mg OD x 5/7
Alternative:
PO cotrimoxazole 800/160mg BD x 14/7
PO beta-lactams x 10-14/7
PO cefuroxime 250mg BD
PO cephalexin 500mg BD
PO augmentin 625mg BD-TDS
May consider initial IV therapy if
(1) severely ill who require hospitalization
(2) cannot tolerate PO decause of n/v
IV ciprofloxacin 400mg BD or
IV cefazolin 1g q8h or
IV augmentin 1.2 q8h and/or
IV/IM gentamicin 5mg/kg
Acute cystitis
in men
Switch to oral therapy when patient has improved or
able to take orally
PO ciprofloxacin 500mg BD x 7-14/7
PO co-trimoxazole 800/160mg BD x 7-14/7
If prostatis is confirmed, treat for 4-6 weeks
These abx are chosen because lipid soluble
concentrates in prostate we are treating for
prostatitis until prostatitis is ruled out
Symptoms of prostatitis: localized pain (perineal,
scrotal, pain on ejaculation, voiding difficultieis,
suprapubic discomfort)
Clincally presented as tender and enlarged prostate
gland on digital rectal exam
Nosocomial/
healthcarerelated
pyelonephritis
IV cefepime 2g q12h +/- amikacin 15mg/kg/day
IV imipenem 500mg q6h
IV meropenem 1g q8h
Duration of therapy: 10-14/7
Catheterassociated UTI
These therapies covers P. aeruginosa and ESBLproducing E. Coli and Klebsiella
IV imipenem 500mg q6h x7/7
IV meropenem 1g q8h x7/7
PO/IV levofloxacin 750mg x 5/7 (if mild infection)
PO co-trimoxazole 800/160mg BD (for women < 65
y/o w/o upper urinary tract smz after indwelling
catheter has been removed)
Duration usually 7 days IF smx resolve within 72h
Extend to 10-14 days if delayed response
Chronic suppressive therapy is not recommended
Standard
prophylaxis
Post-coital
prophylaxis
Prophylaxis
Cotrimoxazole 40/200mg OD or 3x a week
Nitrofurantoin 50mg OD
Trimethoprim 100mg OD
Cephalexin 250-500mg OD
Norfloxacin 200mg OD or 3x a week
Ciprofloxacin 125-250mg OD
Single dose after sexual intercourse
Cotrimoxazole 40/200mg
Nitrofurantoin 50mg
Trimethoprim 100mg
Cephalexin 250mg
