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UTI Microbiology and diagnosis

Dr Lana Sundac LGRS

Urinary tract infections:

Common in both community and hospital setting
o ~2/100 GP visits
o Most common cause of hospital acquired visits
Especially common in women, lifetime risk =40%
Urinalysis makes up bulk of microbiology lab work
Incidence increases with age (uncommon in children, here males more prevalent)
Common in both genders >70

Definitions:
Pyuria leukocytes in urine, can be infections but can also be non-inflammatory
Sterile pyruria leukocytes in urine without growth or culture
Bacteriurea bacteria in urine
o Asymptomatic bacteriuria: patient without symptoms of UTI
o Significant bacteriurea: >105 bacteria/ml of urine (+/- symptoms)
Uncomplicated UTI an UTI in a structurally and functionally normal urinary tract
Complicated UTI an UTI in a structurally or functionally abnormal urinary tract
o Some argue any UTI in men, children or pregnant women is complicated, as are those caused by urinary
catheters or urinary tract stones
Mainly caused by bacteria art of endogenous gut flora

Host defenses exist to prevent UTI:

Urine flow and micturition difficult for bacteria to adhere and move up tract
Antibacterial activity of urine pH, organic acids, urea, osmolality
Urinary tract mucosa itself is protective (cytokines released, bactericidal activity)
Normal kidney secretes complex carbohydrates and proteins that inhibit bacterial adherence to mucosa
o Mucopolysaccharide, Tamm-Horsfall protein
Inflammatory response
o Polymorphonuclear neutrophils (PMNs), cytokines
Innate immune system predominates
o Phagocytosis by polymorphonuclear cells
o Some adaptive immune response: Secretory IgA may also be protective

Predisposing risk factors:

Age ()
Female sex (shorter urethra)
o UTIs mainly caused by bacteria that are part of our endogenous gut flora gain access to sterile area
(urinary tract) infection
Pregnancy changes in immune system function
Sexual intercourse trauma to urethra
Surgery, instrumentation catheter, damage to mucosa
Abnormal renal tract
Immunosuppression (diabetes mellitus, chemotherapy, transplant, corticosteroids)

Renal tract abnormalities

Obstruction to urine flow normal flow is protective mechanism, pooling of urine in bladder creates ideal
environment for bacteria to grow
o Prostatomegaly causes obstruction to outflow tract
o Tumours
o Strictures
o Calculi
Vesicoureteral reflux (VUR)
o Especially in young children, urine refluxes through ureters back up to kidneys
o Congenital abnormality
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o Bladder over-distention
Neurogenic bladder
o Incomplete emptying
o Especially as these patients often require catheterization

Pathogenesis:
Renal tract above level of urethra is normally sterile
Ascending route (most common) bladder infection first reflux
kidney infection
Haematogenous spread (rare) not really UTI but Staph bacteremia
infection that has spread to kidney
Most are caused by endogenous bacteria rather than acquired bacteria
or fomites

Bacterial virulence factors:

Adherence to uroepithelial cells not washed away, promotes
bacterial colonization
o E. coli (has fimbriae), Proteus, Klebsiella, S. saprophyticus,
Enterococcus
Motility ascend renal tract against flow of urine
Urease splits urea, which is a host defense mechanism
Capsule prevents opsonisation
o Klebsiella
Haemolysin invasion, cell damage and iron release
Endotoxins decrease peristalsis

Causative organisms:
Gram negative bacteria Gram positive bacteria less common in UTI
Escherichia coli (E. coli) (main) Staphylococcus spp.
Other Enterobacteriaceae (gut bacteria) o S. saprophyticus (affects healthy, young
o Klebsiella spp. women)
o Proteus spp. o S. aureus (rare, involved via
o Serratia, Citrobacter, Enterobacter, haematogenous route)
Morganella Enterococcus spp.
Pseudomonas aeruginosa (opportunistic Group B Streptococcus
pathogen common in catheterisation, once
colonises can cause infection, but doesnt tend to
cause infection in community)

Uropathogenic E. coli

In lab, urine is placed on agar on plates to grow cultures

Left: (nutrient medium is horse blood agar) E. coli growing creamy, grey colour
Right: another medium initially agar is clear colour until some bacteria which can utilize lactose and ferment it
change pH of medium causing the colonies to turn pink)
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Uropathogenic E. coli has a number of virulence factors to be able to cause UTI

o Can attach to mucosa, ascend bladder, invade tissue, replicate inside cells, attach to ureter via fimbriae
and move to kidney, in kidney can invade renal tissue, and secrete hemolysis (which causes tissue
destruction)
Klebsiella part of Enterobacteriaceae family
o Less common form of UTI
Pseudomonas aeruginosa gram negative bacteria
o Flat colonies on plate
o Good at making biofilms, good at colonizing catheters
Enterococcus faecalis gram positive bacteria
o Breaks down cells in blood agar, clear zones on agar plate
Staphylococcus saprophyticus
o White, creamy colonies
Rare pathogens:
o Corynebacterium urealyticum
o Candida spp. yeast can occasionally cause UTI
o Myobacterium tuberculosis *Tip: TB can cause just about anything
o Viral pathogens: BK virus (pathogen in transplant pts), adenovirus

Community vs hospital acquired infections:

o Different array of bugs that cause UTIs in a hospital setting than in
o Community: Overwhelmingly E. coli (~80%), remaining minority are equally gram positive and negative bacteria
o Hospital: People exposed to resistant bacteria, catheterization introduces, patients microbiome is changed E.
coli still majority, but other GNB that normally wouldnt cause infection in the community, e.g. pseudomonas

Clinical syndromes of UTI:

1. Cystitis
a. Lower urinary tract infection
b. Acute symptoms (pain is symptoms, tenderness on examination)
i. Dysuria (pain when passing urine)
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ii. Frequency + urgency
iii. Suprapubic pain +/- tenderness
c. Recurrent several episodes with different organisms
d. Relapsing several episodes with same organism
2. Pyelonephritis
a. Acute symptoms:
i. Fever
ii. Rigors
iii. Loin pain
b. +/- lower urinary tract infection symptoms
c. Can be complicated:
i. Stones
ii. Obstruction
iii. Abscess
iv. Hydronephrosis
d. Renal tract ultrasound if complication suspected
3. Urosepsis
a. Clinical evidence of UTI, additionally:
b. 2 or more markers of SIRS
i. Temperature: >38 or <36
ii. HR >90bpm
iii. RR >20/min
iv. WCC either high (>12 000/mm3) or low (<4000/mm3), or >10%band forms
4. Urethral syndrome
a. Similar to above, but no significant bacteriuria
b. Dysuria, frequency and urgency
c. Many potential aetiologies
i. Low bacterial count
ii. Fastidious organism, e.g. STI
iii. Atrophic urethritis (reduction of fat stores leads to vagina atrophy shorter urethra)
iv. Pinworm infection
v. Chemical irritant
vi. Mechanical irritant
5. Prostatitis
a. Acute symptoms and signs
i. Fevers, chills
ii. Lower back pain
iii. Perineal pain
iv. Tender prostate on PR exam
b. Chronic prostatitis
i. Vague lower genitourinary pain
ii. Normal prostate on PR exam
iii. May present as recurrent/relapsing UTI
c. Localization studies, e.g. Stamey test
i. Urine examination pre- and post-prostatic massage
Special groups:
Men
o Rare in young men and boys requires investigation
o Incidence with age
<1% in 20-60 age group
3% in 60-70 age group
10% in age >80
o Risk factors: prostatic enlargement, calculi, catheterization, mechanical
abnormality, anal intercourse, lack of circumcision
Children
o Needs investigation
o Risk factors:
Congenital abnormality of the renal tract
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Catheterization
o Neonate and age <2years
Generally unwell, poor feeding
Prolonged jaundice in neonates
Fever, febrile convulsions
o >2yo
Abdominal pain, nausea, vomiting
Crying during micturition, incontinence, enuresis
Fever, febrile convulsion
Elderly
o Common
o Difficult presentation
Fever (may be low grade)
Abdominal pain, nausea, vomiting
Incontinence, dysuria
Confusion
o Predisposing factors:
Women loss of estrogen, atrophy of vagina/urethra
Men urethral strictures, prostatomegaly
Hospitalization
Antibiotics
Catheterization
Women/Pregnant women
o Up to 30% of all GP visits
o 40% lifetime risk
o 1-2% pregnant women experience UTI
o Incidence with age (3% in young women 20% over 80y)
o Risk factors: sexual intercourse, spermicide use, diaphragm vaginitis (menopause), parity, catheterization

Complication of UTI:
Septicemia
Perinephric abscess
Renal scarring
Renal failure
Premature labour
Low birth weight
Rejection of renal transplant
Diagnosis

Diagnosis: specimens
Adults
o Mid stream urine
o * first catch urine for STI because there are vestidious and present in low numbers
Children
o Clean catch urine
o Urine collection bag high change of contamination
Catheter specimen
o In-out catheter if catheter difficult, use this technique introduce into bladder then immediately
take out when sample collected
o Indwelling catheter if long standing, can cause UTI
o *If worried about catheter infection, get a fresh one and take new sample
Suprapubic aspirate straight into bladder
Ureteric aspirate into ureter
Nephrostomy urine into renal pelvis, can be left for weeks
Urine is usually sterile BUT must be collected properly to avoid contamination by urethral and genital flora
o Early morning specimens are best (concentration overnight)
o Midstream urine:
Retract foreskin/labia discard first 30ml urine take next 30ml into sterile container
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o Transport ASAP culture within 2hrs of collection
o Can refrigerate specimen if delay > 2hrs

Diagnosis: Rapid screening

Urine dipstick
Leukocyte esterase test:
o Enzyme released by leukocytes
o 88-94% sensitive for detection of WCC >10
o False positives and false negatives occur
Nitrite reductase test:
o Some bacteria convert nitrate to nitrite
o False negatives
Enterococcus spp, Pseudomonas
If both negative, UTI unlikely

Diagnosis: Laboratory processing

Phase microscopy
o Wet mount
o Cell count normal =<10x106/L
Leukocytes raised in infection/inflammation
Significant if >10x106/L
Erythrocytes bleeding, infection, inflammation
Epithelial cells high number suggests urogenital contamination if >10x106/L
o Bacteria
o Casts (hyaline casts, WBC casts), crystals gout
Normal urine contains <10 leuks, <10 RBC, <10 epithelial

No UTI
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leuk: infection/inflammation
RBC: bleeding
Normal epithelial cells, unlikely
contamination
E.coli growth
=UTI

Leuk:
RBC:
Unlikely contaminiation (normal
epithelial)
Klebsiella pneumoniae growth
= UTI

Leuk could be infection, or

inflammation
Normal RBC
Epithelial
Culture: mixed skin flora

Very likely contamination

Probably not UTI
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Slightly Leuk, but not very high
RBC normal
Epithelial

Urine bag collection = high likelihood of

contamination
Positive E. Coli growth

Could still possibly be UTI

Slightly Leuk
RBC, epithelials

Positive E.coli growth

Probable UTI as in/out technique is

least likely to be contaminated (popped
in to get sample, then removed)
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Unlikely to be contaminied, UTI

mucoid strain - biofilm loving type

- colonising type

Catheter associated UTI

Catheters become colonies with organisms within 48hrs
Most common cause of hospital acquired infection
Treatment with antibiotics ONLY if symptoms present (fever, suprapubic discomfort, loin pain) inappropriate
treatment promotes development of antimicrobial resistance
Asymptomatic bacteriuria:
o Remove catheter if possible
o New catheter if IDC still indicated
In general, remove all unnecessary catheters!

Sterile pyuria:
Prior antibiotic therapy
Foreign body, e.g. catheter, stone
Recent surgery
Glomerulonephritis
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Vaginal discharge
Urethral syndrome
STI, esp. gonorrhoea
Renal tract tuberculosis
Fastidious organisms organism that will only grow when specific nutritional components are available in its diet
(uncommon)

Management of UTI:
1. Uncomplicated cystitis
a. Non-pregnant women
i. Empiric short course (3-5days) of oral antibiotics
1. Cephalexin
2. Trimethoprim
3. Amoxicillin + clavulanic acid
4. Nitrofurantoin
ii. Cultures not mandatory in this group, unless:
1. Recurrent UTI, recent antibiotics, recent international travel due to increased risk of
multi-resistant organisms
b. *If cystitis is suspected in the following groups (men, pregnant women, aged care facility residents,
children) always obtain culture prior to treatment + consider ultrasound
c. Pregnant women
i. While awaiting results, empirical antibiotics (as above) 5 day course
ii. Would not use Trimethoprim targets folate, affect baby
d. Men same empirical agents as above, but 7 day course
2. Acute pyelonephritis
a. Always obtain urine culture (and blood culture in hospitalized patients) prior to antibiotics
b. Mild infection oral antibiotics for 10-14 days
i. Empirical agents as above, N/B: Nitrofurantoin is only used in uncomplicated cystitis
c. Severe infection initial IV therapy
i. Consider imaging to rule out structural abnormality
ii. Ampicillin and Gentamicin; IV
iii. Switch to oral antibiotics (as above) ASAP
iv. 10-14 days in total
3. Recurrent UTI
a. Only investigate and treat if symptoms of UTI present
b. If symptomatic, always culture before antibiotics
c. Investigate for structural or functional abnormality
i. Ultrasound renal tract
ii. Prophylactic antibiotics in very rare circumstances
iii. Stand-by therapy
4. UTI in children
a. May be associated with mechanical abnormality VUR found in 30-50%
b. Need early diagnosis + prompt treatment
c. Always culture before antibiotics
d. Imaging infants, all children with severe/recurrent UTI
i. If required, ultrasound is first line
ii. If USS is normal, no further imaging needed
iii. If USS suggest VUR micturition cystourethrogram
5. Asymptomatic bacteriuria (ABU)
a. Defined as bacterial concentration >108 cfu/L without symptoms of UTI
b. Screening/treatment for ABU not recommended, except for:
i. Pregnant women risk of adverse pregnancy outcomes if bacteriuria progresses to
pyelonephritis
ii. Patients undergoing elective urological procedures
c. For other patient groups, there is no evidence that screening/treatment of ABU has benefit
d. Inappropriate treatment also has risks medication side effects + antimicrobial resistance

Summary:
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Diagnosis of UTI is based on the presence of symptoms
Bacteriuria in properly collected urine, usually associated with pyuria, confirms the diagnosis
Treatment choice depends on the UTI syndrome and patient demographics i.e. Pregnant, male, child
Asymptomatic bacteriuria occurs frequently in elderly people and those with urinary catheters
Screening for, or treatment of, ABU is not recommended except in specific circumstances
o Pregnancy
o Prior to elective urological procedures