Outline

MCQs & EMQ

Definitions

Epidemiology

Case-based Discussions of relevant conditions
MCQ

Which mode of bacterial entry is not a recognised mode of
transmission for UTIs?





Per urethra
Per nasal
Haematogenous
Lymphatogenous
Direct contact
MCQ

Which mode of bacterial entry is not a recognised mode of
transmission for UTIs?





Per urethra
Per nasal
Haematogenous
Lymphatogenous
Direct contact
T
F
T
T
T
MCQ

Which one of the following is not a bacterial pathogenic
factor?





Increase adherence
Resistance of bactericidal properties of serum
Formation of spores
Production of haemolysin
Increased expression of K-antigen
MCQ

Which one of the following is not a bacterial pathogenic
factor?





Increase adherence
Resistance of bactericidal properties of serum
Formation of spores
Production of haemolysin
Increased expression of K-antigen
T
T
F
T
F
MCQ

Which of the following urine findings are typical of
pyelonephritis?





Turbid
High pH
Low specific gravity
High protein
Low RBC
MCQ

Which of the following urine findings are typical of
pyelonephritis?





Turbid
High pH
Low specific gravity
High protein
Low RBC
T
T
T
F
F
MCQ

What is the mechanism of action of Ciprofloxacin?





Interferes with bacterial folate metabolism
Interfere with bacterial DNA gyrase
Inhibits bacterial enzymes and DNA activity
Inhibit bacterial DNA and RNA
Inhibit bacterial cell wall synthesis
MCQ

What is the mechanism of action of Ciprofloxacin?





Interferes with bacterial folate metabolism
Interfere with bacterial DNA gyrase
Inhibits bacterial enzymes and DNA activity
Inhibit bacterial DNA and RNA
Inhibit bacterial cell wall synthesis
F
T
F
F
F
EMQ
A. Enterococcus faecalis

Dorothy is a diabetic, catheterised patient
nearing the end of her course of IV antibiotics
for right lower lobe pneumonia. To top it off
she’s now developed a UTI. What’s the most
likely agent?

Disrupts bladder mucosal integrity and causes
urinary tract obstruction and stasis

Cause of 70-95% of both upper and lower
UTIs.

Associated with UTIs with instrumentation of
the urinary tract due to ‘swarming capability’
(expression of specific genes when these
bacteria are exposed to surfaces such as
catheters)

Possesses UafA (a unique adhesion protein
allowing adherence to human uroepithelial
cells and mediating haemagglutination)
B. Escherichia coli
C. Candida albicans
D. Chlamydia trachomatis
E. Klebsiella pneumoniae
F. Mycobacterium tuberculosis
G. Proteus mirabilis
H. Salmonella typhimurium
I. Schistosoma haematobium
J. Staphylococcus saprophyticus
EMQ
A. Enterococcus faecalis

Dorothy is a diabetic, catheterised patient
nearing the end of her course of IV antibiotics
for right lower lobe pneumonia. To top it off
she’s now developed a UTI. What’s the most
likely agent? C

Disrupts bladder mucosal integrity and causes
urinary tract obstruction and stasis.
I

Cause of 70-95% of both upper and lower
UTIs.
B

Associated with UTIs with instrumentation of
the urinary tract due to ‘swarming capability’
(expression of specific genes when these
bacteria are exposed to surfaces such as
catheters).
G

Possesses UafA (a unique adhesion protein
allowing adherence to human uroepithelial
cells and mediating haemagglutination). J
B. Escherichia coli
C. Candida albicans
D. Chlamydia trachomatis
E. Klebsiella pneumoniae
F. Mycobacterium tuberculosis
G. Proteus mirabilis
H. Salmonella typhimurium
I. Schistosoma haematobium
J. Staphylococcus saprophyticus
Definitions

Bacteriuria


The presence of bacteria in the urine (>104 colony-forming units (cfu)
per ml of urine)
Urinary tract infection (UTI): inflammatory response secondary to
bacteriuria

At least one of the following symptoms or signs, with no other
recognised cause:




Fever>380C in a patient aged ≤65 years of age
Lower urinary tract symptoms (urgency, frequency, dysuria, suprapubic
tenderness, loin pain)
A positive urine culture of ≥105 cfu/ml with no more than two species
Uncomplicated UTIs: acute cystitis and acute pyelonephritis


Otherwise healthy individuals
mostly in women without structural and functional abnormalities
Definition

Pathogenicity


the ability of an organism to cause disease
Virulence

the degree of pathogenicity
Epidemiology
Age (y)
Female (%)
Male(%) Risk factors
<1
0.7
2.7
Foreskin, Abnormal anatomy
1-5
4.5
0.5
Abnormal anatomy
6-15
4.5
0.5
Abnormal function
16-35
20
0.5
Sex, diaphragm
36-65
35
20
Surgery, BOO, Catheter
>65
40
35
Incontinence, Catheter, BOO
• 50% of UTIs do not come to
medical attention
• Lifetime prevalence
• 14 per 100 men
• 53 per 100 women
• Most UTI single organism. E.Coli: 80%
• Community
•
Klesiella, proteus, enterobacter
• Hospital
•
Staph, pseudomonas
• Pregnancy
•
GpB Strep
• Children
•
Klebsiella, enterobacter
Case 1

22y female, pyrexial. Dysuria and frequency

How would you assess the patient?

Focused history






Relevant examination



Lower urinary tract symptoms
Systemic and associated symptoms
Triggers (sexual intercourse, cyclical)
Past/childhood history  Normal urological tract
Absence of vaginal discharge
Abdominal
?PV
Investigations


Urine Dipstick may be sufficient
MSU
Pathogenesis – Bacterial Factors
4 modes of bacterial entry


Per Urethra (most common)

Ascending

Explains why female>male
Haematogenous


Lymphatogenous (?)


S. Aureus, Candida spp,
TB
Rectal, colonic, uterine
Direct spread

Fistulas, abscesses

Bacterial pathogenic factors

Increased adherence

Resistance to bactericidal
activity of human serum

Increased expression of K
capsular antigen (protects from
phagocytosis)

Production of haemolysin

Invasion of host cells – biofilms
(uroplakin coated)
Pathogenesis – Host Factors

Unobstructed urine flow




Urine characteristics






Blood group antigens – prevent bacterial adherence
Normal flora




GAG-layer
Toll-like receptors (TLR) – inflammatory mediators (IL-8Neutrophils)
Serum and urinary antibodies (defense vs damage)
Bacterial binding sites (> in females with recurrent UTIs)
Genetics


Osmolality, pH, urea conc, organic acid conc
Tamm-Horsfall glycoprotein: inhibit adherence
Urothelium


Washout of bacteria
Stasis/retention : BOO, neurological, diabetes, pregnancy
Reflux – allows ascent of bacteria
Women periurethral area: lactobacillus
Altered by antibiotics, low estrogen, faecal incontinence
Men prostatic secretions: zincantibacterial
Foreign bodies (catheters, stents, stones)

Allows bacteria to hide from host defense
Case 2
Diagnosis & Investigations

Urine sample


MSU, SP aspiration, In/out catheter
Urinalysis



Leucocyte esterase: breakdown of WBC
Nitrites: Breakdown of nitrates by GNB
Dipstick: negative for blood, nitrite, leucocyte and protein:
<2% positive culture
Test
Sensitivity (%)
Specificity (%)
Leucocyte esterase
83
78
Nitrite
53
98
WBC
73
81
Interpreting urinalysis

Appearance: clear


pH: Normal values 4.5-7.2


Alkaline: infection
Specific gravity: Normal values 1.005 to 1.025


Turbid: infection
Low in pyelonephritis
Protein: Normal 0-trace

Renal disease
Flow Cytometry

Flow cytometry



Fully automated (eg
Sysmex UF-100)
Measures impedance of
particles in urine
Uses 2 fluorescent dyes

Carbocyanine: stains the
cell membrane

Phenanthridine stains
nucleic acids
Clinica Chimica Acta, Volume 301, Issues 1–2, November 2000, Pages 1-18
Culture

Urine plated on agar (specific loop size)

Incubated for 24-48 hours, 370C in air

Plates read: positive >103-5 cfu/ml

Identification of bacteria



Biochemical (eg API)
Molecular (bacterial DNA and PCR)
Sensitivity



Conditions of growth (agar, conditions)
Antibiotics strips
Bacterial genes detected by PCR
Case 3

22y female, pyrexial, shakes & shivers, right loin pain, vomiting.
Dysuria prior to this episode.

E. Coli in urine

How would you manage this patient?

How would you assess the patient?

Focused history






Lower urinary tract symptoms
Systemic and associated symptoms
Triggers (sexual intercourse, cyclical)
Past/childhood history  Normal urological tract
Absence of vaginal discharge
Relevant examination


Abdominal
?PV
Acute Pyelonephritis

Inflammation of kidney and renal pelvis

Sepsis (20-30% of all sepsis urological)


USS



IV Abx if pyrexial or bacteremic
Rule out obstruction
Poor at diagnosing inflammation
CT Findings




Enlarged kidney
Stranding
Perfusion defects & attenuated areas (constriction of peripheral
arterioles) – can be seen on a nuclear scan
Compression of collecting system
Escherichia Coli

Gram-negative rods

Part of the lower gastrointestinal microbiome

Sero-groups O, K and H

Pilli (tips of bacterial fimbriae) - Binds to glycoproteins/lipids on
urothelium

Internalisation of bacteria: bacterial persistence

P pili: can bind to urothelial cells, RBC, renal tubular cells


90% of E.Coli pyelonephritis
Type 1 pili: can bind to urothelium

Increases bacterial adherance

More common in cystitis
International Journal of Medical Microbiology Volume 297, Issue 6, 15 October 2007, Pages 401–415
Case 4

OP department, 18y female, recurrent UTIs

Management

Focused history






Relevant examination



Lower urinary tract symptoms
Systemic and associated symptoms
Triggers (sexual intercourse, cyclical)
Past/childhood history  Normal urological tract
Absence of vaginal discharge
Abdominal
?PV
Investigations


Urine (Dipstick + MSU)
?USS + Flexi
Recurrent Bladder Infection
Bacterial persistence




USS: Screening evaluation of
urological tract
CT: Detailed anatomy
Localisation studies

Ureteric catheter and fluid
sent for culture
Management: removal of cause
(eg stone, PUJO, BPH)
Bacterial re-infection

Assessment for fistula

Imaging not necessary

Management: Fistula
repair, Abx prophylaxis
• ABx Prophylaxis: can reduce UTIs episodes by 95%
• Regular voiding (increase oral intake)
• Cranberry juice
• Estrogenisation of introitus
• Self-medicated Abx
• After sex
• When patient feels onset of symptoms
Antibiotics

Bacterial susceptibility


Organism, hospital vs community, single vs polymicrobial
Patient characteristics

Allergies, age, previous Abx, pregnancy, PO vs IV
Antibiotics
Mechanism
Action
Septrin
(co-trimoxazole)
Interferes with bacterial folate
metabolism
Most UTIs except enterococcus and
pseudomonas
Floroquinolones
Interfere with bacterial DNA gyrase,
preventing replication
GNB, Staph but not Strep
Nitrofurantoin
Inhibits bacterial enzymes and DNA
activity – long term use may lead to
pulmonary interstitial changes
GNB (except pseudomonas and proteus),
Staph and enterococci
Aminoglycosides
Inhibit bacterial DNA and RNA
GNB, Enterococci (with ampicillin)
Cephalosporins
Inhibit bacterial cell wall synthesis
GNB, GPB (3rd generation better for
former)
Penicillins – only
amoxicillin/ampicillin
Inhibit bacterial cell wall synthesis
GNB (with clavulanic acid)
Antibiotics

Antibiotics resistance INCREASING

Geographical variability

E. Coli


up to 50% to ampicillin

Up to 27% to trimethroprim

Up to 49% to septrin

Up to 30% to floroquinolone
Only 25% of ABx use for ‘UTIs’ have documented bacteriuria

50% for LUTS

25% prophylaxis
Case 5

35 year old female, 18 weeks pregnant, right loin pain,
pyrexial, positive urine dipstick

Urine MC&S

Serratia marcescens

Amoxicillin – R
Cefelexin – R
Trimethoprim – R
Tazocin – R
Gentamicin - S




UTI in pregnancy

Pregnancy changes


Renal length increases & GFR increases by 30-50% (secondary to CO)
Ureteral dilatation with stasis




Bacteriuria should be treated in pregnancy and eradication confirmed
Pyelonephritis



Increase in bladder capacity + hyperemia
Bacteriuria 4-6% 30% (vs 2%) develop pyelonephritis


smooth muscle relaxing (progesterone)
Physical compression at pelvic brim
1-4% of pregnant women
If untreated  Prematurity of fetus and perinatal abnormality
Penicillin, Cephalosporins safe

Gentamicin: FDA pregnancy category D. Safety of gentamicin has not been
established; potential benefit should outweigh the potential risk.
Aminoglycoside
(Gentamicin)

Inhibit bacterial DNA and RNA

Together with ampicillin, has GP cover



Nephrotoxicity




Bactericidal synergy
Gentamicin decreases lytic effect of penicillin
Excessive accumulation in PCT cells : 40 – 50 times than in blood
Direct effect on GFR
Toxicity reversible initially- renewable PCT cells
Ototoxicity



Vestibular and auditory dysfunction
Accumulate in perilymph & endolymph
Irreversible
J Antimicrob Chemother. 1990 Apr;25(4):551-60.
Gentamicin dosing

Pharmacokinetics




Small volume of distribution (0.25l/kg)
Half life: 2-3 hours
Mainly renal clearance (glomerular filtration)
Loading vs maintenance dosing

Antimicrobial effect is concentration dependent

Once daily (more common) vs multiple dosing

Therapeutic dose monitoring
Hartford Regime

7mg/kg, serum concentration at 12 hours

Efficacy: Minimum inhibitory concentration (MIC) reached
2184 patients
1.2% reversible nephrotoxicity
0.14% ototoxicity
Antimicrobial Agents and Chemotherapy March
1995 ; 39 : 650-655
Summary

Very common but can be very serious

Urologists tend to be involved with complex UTIs




Anatomical considerations
Iatrogenic
Urological pathology?
Antibiotics is effective but should not be abused

Follow local guidelines
References

EAU guidelines

Comprehensive Urology

Previous slides from Milan Thomas

Pubmed