Microbiology Of Utis

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Urinary Tract and UTIs

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MIcrobial Causes of UTI

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• Usually monomicrobial disease
• Bacteria (common)
– Gram-negative (Escherichia coli, Klebsiella species,
Proteus, Enterobacter etc)
– Gram-positive (Staphylococcus saprophyticus,
Enterococcus)
• Viruses
– Adenoviruses, enteroviruses
• Fungi (rare)
– Candida albicans

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Cllassssiifiicattiion

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• Uncomplicated
– Occur in a structurally and functionally intact urinary
tract
– Example: acute cystitis
• Complicated
– Occur in an abnormal urinary tract or in the presence
of risk factors
– Example: acute pyelonephritis
– Higher risks of getting UTI or of treatment failure
– The spectrum of complicated UTIs may range from
recurrent cystitis to urosepsis and septic shock

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Risk Factors:
Uncomplicated UTI

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• History of previous UTI
• Frequent or recent sexual intercourse
• Pregnancy
– urethral dilatation
– changes in bladder volume and tone
• Urinary incontinence (e.g., in postmenopausal women)

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Risk Factors:
Complicated UTI

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• Children (<12 years of age)
• Obstruction of bladder outflow
– congenital abnormalities
– prostatic enlargement
– upper tract calculi or bladder stones
• Presence of indwelling catheter

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Host Defences

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• Low vaginal pH (3.5-4.5) (due to lactic acid
produced by Lactobacilli) and normal flora
suppress colonization by uropathogens
• Normal acid pH of urine (4.6-6) is anti-bacterial
• Complete bladder emptying is a major protective
factor
• Reduced urine flow or accidental introduction of
bacteria into the bladder can lead to cystitis

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Bladder Pumping

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UTI more common in women

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• Short urethra with turbulent flow that washes urethral
organisms into the bladder during micturition
• Close proximity to perianal areas

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Recurrent Cystitis

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• Up to 27% of young women with acute cystitis develop recurrent UTIs
• Relapse: infection with [partially treated] same
microorganism (multiple relapses = complicated UTIs)
• Recurrence: infection with different organisms
• The causative organism should be identified by
urine culture

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Prevalence of UTI according to age

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Common uropathogens
-Mode of transmission
-Treatment
-Distinctive features

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Pathogenesis of UTI

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Haematogenous Spread

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Haematogenous seeding of renal cortex less frequent than ascending infection

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Risk Factors for Bacteraemic UTI

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Virulence factors of Coliforms

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• Escherichia coli strains expressing O-antigens O1, O2, O4, O6, O7, O8, O75, O150 cause high proportion of infections
• Capsular K1, K5, and K12 antigens of E. coli associated with clinical severity (antiphagocytic)
• P-fimbriae enhance attachment of E. coli to receptors of uroepithelial cells
• Flagella allow motile bacteria to ascend the ureter against urine flow
• Gram-negative endotoxin decreases ureteral
peristalsis
• Haemolysin damages renal tubular epithelium
and promotes invasive infection
• Bacterial urease (Proteus)
– splits urinary urea with generation of ammonium ion
that alkalinizes urine with loss of acid pH as natural
defense barrier against infection
– stone formation with ureteral obstruction and survival of bacteria deep within stones resisting eradication by antibiotic and immune cells

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Normal Biota of the urinary tract

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• The gut is home to our largest population of microbes
• Outer region of the urethra harbour normal
bacterial flora
– Non-haemolytic streptococci, staphylococci,
corynebacteria and lactobacilli
– Urine is a growth medium for many bacteria and yeast

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Pathogenicity Islands

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• PIs carry virulence genes
– Present in uropathogenic faecal strains
– Large size (10-100Kb) and different G+C content from
host chromosome - “foreign” DNA
• Unstable, prone to deletion

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Drugs

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• Beta-lactamase-resistant antibiotics
– Cephalosporins – Cefotaxime, Ceftriaxone
– Carbapenems - Meropenem
• Beta-lactamase inhibitors

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Resistance

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- ESBL
• KPC – Klebsiella pneumoniae Carbapenemase
– Occurs in E.coli, Klebsiella, Enterobacter, Pseudomonas
aeruginosa

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Must ID the Pathogen

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Why is UTI important?

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• Leading cause of morbidity and health care
expenditures
– ~50% of women report having a UTI at some point in
their lives, >25% of women experience a recurrence
– UTI in pregnancy – increased risk of intrauterine growth
restriction and preterm delivery
– Present in 1-16% of febrile infants and children
• Significant mortality of complicated UTIs
– Escherichia coli associated bacteraemia – 5-20%
mortality
– Drug resistant pathogens increase mortality up to 60%

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PK of A/B used to Tx UTIs

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Front 23

Complicated vs Uncomplicated UTIs
- comparison

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Spectrum of pathogens

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E.Coli Susceptibility

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Microbiological Dx of UTI

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• Blood culture – positive BC is usually significant
• Urine culture – prone to contamination
– Urine within a bladder is sterile but as it passes
through the urethra it often becomes contaminated
with a small number of bacteria
– Thus specimens should reach laboratory within 4
hours of voiding
• When to order urine culture?
– Complicated UTI (e.g., clinical features of
pyelonephritis)
– Patients at risk for complicated UTI
– Failure to respond to empirical treatment

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Urine Specimens

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• Spontaneous voiding
– First morning specimen – most concentrated, with
higher levels of cellular components and protein
– Midstream clean catch specimen – preferred for UTI
because of reduced incidence of contamination
– Bag urine – prone to contamination
• Urethral catheterisation
– When patient is bedridden/cannot urinate independently
– In/out (Foley) catheter or indwelling catheter
• Supra-pubic bladder aspiration
– Needle aspiration through abdominal wall

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Urine Ix

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• Three lines of evidence
– Urine dipstick analysis
– Direct microscopy
– Bacterial culture (with susceptibility testing of a
potential pathogen)

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1. Dipstick

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Up to 10 analytes including:
• Leukocytes – detection of pyuria
• Blood – detection of haematuria
• Protein – detection of proteinuria
• Glucose – detection of glucosuria
• Nitrite
• Bilirubin
• pH (between 4.5 and 8)
Test results are read as colour
changes on test strip
Specimen A – cloudy and
leucocyte –ve but nitrite-positive
Specimen B – clear and dipsticknegative

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Dx potential of Dipstick

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• Diseases of the kidneys and the urinary tract
– Detection of leukocytes - pyuria (detection limit 107
cells/L)
– Detection of blood – haematuria (detection limit 106
RBC/L)
– Nitrites (positive test = presence of ≥104 organisms/L)
– Protein (<2g/24 hours suggestive of UTI; >3g/24 hours –
underlying renal disease)
• Carbohydrate metabolism disorders
– Detection of glucose (diabetes mellitus)
• Liver diseases
– Detection of bilirubin

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2. Urine Microscopy

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Casts

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Crystals

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Bacterial Culture;
which organisms to look for

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3. Culture Plate method

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• Quantitative methods discriminate contamination
and colonisation from infection
• Calibrated loop (5-10 μL of urine)
• Colony count after 18-24 hours of incubation
– Expressed as Colony Forming Units (CFU) per Litre

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+ve culture

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• Positive culture or significant growth
– Midstream urine ≥ 108 of CFU/L
– Catheter urine ≥ 104 CFU/L
– Supra-pubic aspirate – any growth is significant
– Sensitivity for cystitis ~60%
– Less diagnostic for UTIs in elderly and children e.g.,
any growth from supra-pubic aspirate sample should
be reported
• Mixed growth suggests contamination

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Significant vs non-significant growth

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Significant BActeriuria

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Alogorithm Dipstick first

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Algorithm Microscopy + Culture

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Epithelial cells

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Summary

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Front 43

Pyuria

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pus in the urine

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Conditions with sterile pyuria

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• Infectious
– Prior antibiotic therapy
– Fastidious microorganisms (e.g. Mycobacterium
tuberculosis, Chlamydia trachomatis, Neisseria
gonorrhoeae, Leptospira, human adenovirus)
• Non-infectious
– Genitourinary trauma or tumour
– Prostatitis
– Glomerulonephritis or nephropathy
– Vaginal contamination

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Ix in UTIs

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- FBC;
- WCC looking for bacteriemia
- CRP: can indicate inflammation and in some elederly patients the WCC count may not rise and infection cannot be excluded without both WCC and CRP
- urine dipstick
- EUC
- CXR
- PVR bladder
- rectal exam (impaction can cause UTI, blood, anal tone...)

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Therapeutic Guidlines

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- emoiric therapy
- urine culture before A/B use
- alkalinising agents improve Sx, but dont improve AB efficacy and can increase crystalluria, so not advised
- high fluid intake and complete bladder emptying assist antimicrobial therapy

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Which A/B?

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trimethroprim
cephalexin
amoxycillin calvulinte
nitrofurantoin

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UTIs in elderly

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- common
- asymptomatic bacteriuria 10-20% of cases and need to DDx from UTI

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Nitrites

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G-ve coliforms can reduce nitrates to nitrites in urine, but not other organisms, so neg nitrities does not exclude UTI

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How does diagnosis of UTI differ in pregnancy?

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•Urinary tract infections are common in pregnant women but so are the symptoms
•All pregnant women should be screened for the presence of bacteruria

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How does the management of UTI differ in pregnancy?

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•The initial choice of antibiotics should be guided by local microbiology and susceptibility data.
•Pyelonephritis should be treated with hospitalization and intravenous antibiotics until the woman is afebrile for 48 hours and symptomatically improved
•Oral therapy (guided by culture susceptibility results) and discharged to complete 10 to 14 days of treatment

•Recurrent pyelonephritis during pregnancy occurs in 6 to 8 percent of women.
•Therefore, low dose antimicrobial prophylaxis with an agent to which the organism is susceptible is warranted for the remainder of the pregnancy
•Nitrofurantoin (50 to 100 mg orally at bedtime) or cephalexin (250 to 500 mg orally at bedtime)

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What are the risks of UTI in pregnancy?

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•Physiologic changes of pregnancy:
•Hydronephrosis, vesicoureteral reflux
•Increased bladder capacity, incomplete emptying
•Increased urine pH during pregnancy

•Coexistent factors:
•Urinary anomalies, calculi, multiple UTI’s
•Dehydration, poor hygiene
•Resistant organisms, Rx noncompliance
•Diabetes, Sickle disease

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Asymptomatic bacteriuria

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•Diagnosis is by isolation of microorganism with a colony count of >105 organisms per ml of urine in a clean catch specimen: done at at 12 to 16 weeks gestation (or the first prenatal visit, if that occurs later)
•Is associated with an increased risk of preterm birth, low birth weight, and perinatal mortality
•Untreated 40% will develop symptom of UTI.
•About 25-30% will develop acute pyelonephritis, but wth treatment the rate is only 10%.
•Treatment of bacteriuria during pregnancy reduces these complications
•Short course (3-7 days) with sensitive antibiotics, appropriate for pregnancy
•Retest MSU one week after finishing course, then monthly until pregnancy finishes
•Suppressive therapy may be required if bacteriuria persists after two or more courses

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Acute cystitis

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•Presents with frequency, urgency, dysuria and suprapubic dyscomfort.
•Same approach to management as with symptomatic bacteriuria
•Follow up the same as with asymptomatic bacteriuria

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Acute pyelonephritis
- in pregnancy

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•Occurs in 1-2% of all pregnant women
•Maternal complications include anaemia, bacteraemia, respiratory insufficiency, and acute kidney injury.
•As many as 20 percent of women with severe pyelonephritis develop complications that include septic shock syndrome or its variants, such as acute respiratory distress
•Pregnancy outcomes —The strength of the association between acute pyelonephritis and adverse pregnancy outcomes is less strong than with asymptomatic UTI , perhaps because of confounding variables such as socioeconomic status and previous preterm delivery.
•Preterm labor and foetal death can occur in severe cases.

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Pyelonephritis in Pregnancy Common pathogens

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•Escherichia coli 70 – 80%
•Klebsiella sp 3 – 7.4%
•Staph aureus 6.7%
•Proteus mirablis 2%
•Gram positive (includes GBS) 10%