Uncomplicated Urinary Tract Infections

Amar MoheeMilan Thomas

Steve Bromage

18th April 2013

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 T Per nasal F Haematogenous T Lymphatogenous T Direct contact 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 T Resistance of bactericidal properties of serum

T Formation of spores F Production of haemolysin T Increased expression of K-antigen 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 T High pH T Low specific gravity T High protein F Low RBC 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 F Interfere with bacterial DNA gyrase T Inhibits bacterial enzymes and DNA activity

F Inhibit bacterial DNA and RNA

F Inhibit bacterial cell wall synthesis F

EMQA. Enterococcus faecalis

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

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)

EMQA. Enterococcus faecalis

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

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

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

EpidemiologyAge (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

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

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

S. Aureus, Candida spp, TB

Lymphatogenous (?) 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

Washout of bacteria Stasis/retention : BOO, neurological, diabetes, pregnancy Reflux – allows ascent of bacteria

Urine characteristics Osmolality, pH, urea conc, organic acid conc Tamm-Horsfall glycoprotein: inhibit adherence

Urothelium GAG-layer Toll-like receptors (TLR) – inflammatory mediators (IL-8Neutrophils) Serum and urinary antibodies (defense vs damage) Bacterial binding sites (> in females with recurrent UTIs)

Genetics Blood group antigens – prevent bacterial adherence

Normal flora Women periurethral area: lactobacillus Altered by antibiotics, low estrogen, faecal incontinence Men prostatic secretions: zincantibacterial

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

Turbid: infection

pH: Normal values 4.5-7.2 Alkaline: infection

Specific gravity: Normal values 1.005 to 1.025 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) IV Abx if pyrexial or bacteremic

USS 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

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

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

smooth muscle relaxing (progesterone) Physical compression at pelvic brim

Increase in bladder capacity + hyperemia

Bacteriuria 4-6% 30% (vs 2%) develop pyelonephritis Bacteriuria should be treated in pregnancy and eradication confirmed

Pyelonephritis 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 Bactericidal synergy Gentamicin decreases lytic effect of penicillin

Nephrotoxicity 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

Antimicrobial Agents and Chemotherapy March 1995 ; 39 : 650-655

2184 patients

1.2% reversible nephrotoxicity0.14% ototoxicity

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