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EVALUATION SEMINAR ON

PRESENTED TO
Dr. Santhrani Thaakur

P.Bindu
M.Pharmacy 1st year
Contents
 Introduction
 Terminology
 Classification of UTI
 Epidemiology
 Etiology
 Pathogenesis
 Risk factors
 Clinical presentation
 Diagnosis
 Treatment
 Conclusion
 References
Introduction
• Symptomatic
presence of micro
organisms within the
urinary tract
i.e., kidney, ureters,
bladder and urethra.

• Associated with
inflammation of
urinary tract.
• Significant bacteriuria: presence of at least
105 bacteria/ml of urine.

• Asymptomatic bacteriuria : bacteriuria with


no
symptoms.

• Urethritis: infection of anterior urethral tract


*dysuria, urgency and frequency of urination.

• Cystitis: infection to urinary bladder


*dysuria, frequency and urgency, pyuria and
• Acute pyelonephritis: infection of
one/both kidneys; sometimes lower tract
also.
*pyuria, fever, painful micturition

• Chronic pyelonephritis: particular type of


pathology of kidney; may/may not be
due to infection.
UTI - Terminology
• Uncomplicated: UTI without underlying renal or
neurologic disease.

• Complicated: UTI with underlying structural,


medical or neurologic disease.

• Recurrent : > 3 symptomatic UTIs within 12


months following clinical therapy.

• Reinfection: recurrent UTI caused by a different


pathogen at any time

• Relapse: recurrent UTI caused by same species


causing original UTI within 2 wks after therapy.
UTI

Upper Lower
•Acute pyleonephritis •Cystitis
•Chronic pyleonephriitis •Prostatitis
•Interstitial pyleonephritis •Urethritis
•Renal abscess
•Perirenal abscess

•Both upper & lower UTI are further divided into


complicated and uncomplicated.
Epidemiology
 Seen in all age groups
 Infants up to 6 months – 2/1000
 More common in boys than girls

 Women – at greater risk than men; prevalence


40-50% in women and 0.04% in men.
 10% women have recurrent UTI in their life
 7 million new cases of lower UTI / year
 1 million hospitalizations / year

 Incidence of UTI increases in old age; 10% of


men and 20% of women are infected.
Etiology
• Acute uncomplicated UTI:
• Escherichia coli – cause about 80% of UTI
• 20% of UTI caused by-
Gram negative enteric bacteria – Klebsiella,
Proteus
Gram positive cocci – Streptococcus
faecalis
Staphylococcus saprophyticus
• S.saprophyticus – restricted to infections in
young sexually active women.
Complicated UTI:

 Pseudomonas aeruginosa, Enterobacter &


Serratia

 Isolated in hospital acquired infections and


catheter associated UTI.

 Viruses - Rubella, Mumps and HIV

 Fungi - Candida, Histoplasma capsulatum

 Protozoa - T. vaginalis, S. haematobium


Pathogenesis
• 4 routes of bacterial entry to urinary
tract.

1) Ascending infection

2) Blood borne spread

3) Lymphatogenous spread

4) Direct extension from other organs


• Ascending Infection:
 most common route.
 organisms ascend through urethra into
bladder.
organism

Colonize in
perineal and
periurethral areas

Ascend to
bladder,
kidneys
UTI
• Hematogenous
spread:

 Blood borne
spread to kidneys.

 Occurs in
bacteraemia
mostly S.aureus.
• Lymphatogenous spread:
 Men- through rectal and colonic
lymphatic vessels to prostrate and
bladder.
 Women- through periuterine lymphatics
to urinary tract.

• Direct extension from other organs:


 Pelvic inflammatory diseases
 Genito-urinary tract fistulas
• The organism:
 E.coli – many strains present but only few
cause infection.

 Virulence factors:
1. fimbriae
2. resistance to serum bactericidal activity
; increased amounts of capsular K antigen
activity
3. toxin production
4. production of urease enzyme (proteus
sps)
Vesiculourethral reflux
UTI – RISK FACTORS
1. Aging: diabetes mellitus
urine retention
impaired immune system

2. Females: shorter urethra


sexual intercourse
contraceptives
incomplete bladder emptying with age

3. Males: prostatic hypertrophy


bacterial prostatis
age
UTI-CLINICAL PRESENTATION

• Clinical manifestations depending on


site of infection

• Clinical manifestations depending on


age of patient
Clinical manifestations depending on site
of infection

• Urethritis:

 Discomfort in voiding
 Dysuria
 Urgency
 frequency
• Cystitis:
 dysuria, urgency and frequent
urination
 Pelvic discomfort
 Abdominal pain
 Pyuria

• Hemorrhagic cystitis:
 Visible blood in urine.
 Irritating voiding symptoms
• Pyleonephritis:

 Invasive nature
 Suprapubic
tenderness
 Fever and chills
 White blood cell casts
in urine
 Back pain
 Nausea and vomiting
Complications include sepsis, septic shock
and death.
Clinical manifestations depending on age
• Babies and infants:
 Failure to thrive
 Fever
 Apathy
 Diarrhoea

• Children:
 Dysuria, urgency, frequency
 Haematuria
 Acute abdominal pain
 Vomiting
• Adults:
 Lower UTI- frequency, urgency,
dysuria,
haematuria
 Upper UTI- fever, rigor and lion pain
and symptoms of lower UTI.

• Elderly patients:
 Mostly asymptomatic
 Not diagnostic as the symptoms are
common with age.
UTI- DIAGNOSIS
• Microscopic examination of urine

• Urinalysis

• Urine culture

• Imaging techniques – CT scan and MRI


Laboratory examination
• Uncontaminated, midstream urine sample
used.

• Methods for urine collection:


1. stick on bags
2. catheterization
3. suprapubic aspiration(SPA) –
gold standard for urine collection
Laboratory findings
Normal Findings Abnormal findings
• pH - 4.6 – 8.0
• Appearance- clear •pH – Alkaline (
increases)
• Color – pale to amber • Appearance – cloudy
yellow
• Color - deep amber
• Odor – aromatic
• Blood – none • Odor – foul smelling
• Leukocyte esterase – •Blood – maybe present
none
•Leukocyte esterase -
• WBC- absent present
•WBC- present
• Bacteria- absent
•Bacteria- present
Urinalysis :
• Presence of pus, white
blood cells, red blood
cells

• Bacterial count > 105 /ml –


significant bacteriuria

• Leukocyte esterase
dipstick test – WBC in
urine

• Nitrite dipstick test- pink


colour
Urine culture :

 For pyelonephritis

 Not a rapid diagnostic tool

 >105 bacteria /ml

 Differential leukocyte count- Urine culture


increased neutrophils
Diagnostic tests for adults with recurrent
UTI
• Intravenous pyelography / excretory
urography
• Voiding cystourethrography

• Cystoscopy

• Manual pelvic and


prostrate
examination
UTI

urinalysis

Urine microscopy and culture

Further investigation

pyelonephriti
Adult female Male s Children
Lower UTI Any UTI Complicated Any UTI

Treat without Blood


further Ultrasound cultures cystourethro
investigation cystoscopy CT scan graphy
Check renal
UTI - management
• Symptomatic UTI- antibiotic therapy

• Asymptomatic UTI- no treatment required


except in special situations.

• Non- specific therapy:


• more water intake.

• Maintaining acidity of urine by fluids like


canberry juice.
Anti-microbial therapy
• Goals of therapy:
 Elimination of infection
 Relief of acute symptoms
 Prevention of recurrence and long
term complications

• Decision to hospitalize ??

• Treatment considerations ??
• Ideal antibiotic for UTI :

 Adequate coverage over E.coli


 Concentration in urine
 Duration of therapy
 Low resistance
 Cost
 Low adverse effect profile
Principles of anti microbial therapy

• Levels of antibiotic in urine but not in


blood

• Blood levels of antibiotic – important in


pyleonephritis

• Penicillins and cephalosporins – drugs of


choice for UTI with renal failure.
treatment duration

• Single dose therapy

• 3 day course

• 7 day course

• 10 – 14 day course
Single dose therapy
a. Trimethoprim- sulfamethaxole
bactrim–DS : TMP–160mg + SMZ–800mg
co-trimoxazole-DS :TMP-160mg + SMZ-800mg

b. Amoxicillin- clavulnate 500mg


aceclav tab
acmox- AG tab
c. Amoxcillin 3gm

d. Ciprofloxacin 500mg – alquin tab


e. Norfloxacin 400mg – Actiflox-400 tab
• for uncomplicated UTI

• Not for patients with


1. past history of complicated UTI
2. history of antibiotic resistance
3. history of relapse with single dose

• advantages: compliance, cost, less side


effects, less resistance
• Disadvantages: increased recurrence or
relapse
3 day therapy
• Efficacy same as 7 day therapy with less
adverse effects
• Drugs used include
1. quinolines
2. TMP-SMZ
3. betalactam antibiotics

• Extended release ciprofloxacin


500mg for uncomplicated UTI
1000mg for complicated UTI
7 day therapy
• Used less for uncomplicated UTI
• Useful in 1. recurrent cases
2. pregnancy
3. UTI with other risk factors

14 day therapy

• For complicated UTI


• High risk of mortality and morbidity
Pathogen specific treatment
Pathogen Treatment options
Escherichia coli Ceftriaxone 50mg/kg i.v
/I.M Qday

Pseudomonas Gentamycin 6-7.5mg /kg


aeroginosa i.v Q8hr / Qday
Klebsiella sps
Enterobacter sps Ceftadizine 100-
Proteus sps 150mg/kg/day i.v Q8hr

Enterococcus sps Ampicillin 100-


200mg/kg/day Q6hr
Infection specific treatment
Lower UTI
 3day therapy preferred

*Trimethoprim Cephalaxin

*Nitrofurantion *ciprofloxacin

Amoxicillin *Co-amoxiclav

Norfloxacin
Antibiotic Dose Side effects contraindications
Co-amoxiclav 375mg nausea, diarrhea, Penicillin
every rashes, hepatitis hypersensitivity
8hr
Trimethoprim 200mg Nausea, vomiting, Severe renal
every pruritis, rashes failure, neonates
12hr
Ciprofloxacin 250mg Nausea, vomiting, CNS disorders
every dizziness, Pregnancy
12hr convulsions, Children
hallucinations, G6PD deficiency
hepatitis, blood
disorders,
photosensitivity
Nitrofurantoin 100mg Nausea, vomiting, Renal failure
every peripheral Neonates
12hr neuropathy, Porphyria
pulmonary G6PD deficiency
reactions
Acute pyelonephritis
• Paranteral antibiotics
• Cefuroxime – 750mg i.v. Q8h
Gentamycin - 80-120g i.v. Q12h
Ciprofloxacin – 200mg i.v. Q12h

• 10-14 days treatment

• Ceftazimide, imipenam, ciprofloxacin –


for hospital acquired pyelonephritis
Asymptomatic bacteriuria
• Children – treatment same as
symptomatic bacteriuria

• Adults –
treatment required in cases of
a. pregnancy
b. patient with obstructive structural
abnormalities
Bacteriuria in pregnancy
• To prevent risk of pyelonephritis

• 7 day course with following antibiotics


 Cephalaxin
 Nitrofurantoin
 Amoxicillin

• Therapy continued at regular intervals


of pregnancy.
Relapsing UTI
• 7-10 day course
• If fails – 2week course / 6week course

• Structural abnormalities corrected by


surgery
• 6week course –
a. children
b. adults with continuous symptoms
c. high risk of renal damage
Prophylaxis for UTI
• Single dose of trimethoprim 100mg /
nitrofurantion 50mg

• Long term low dose prophylaxis


beneficial

• Women- single dose of antibiotic after


sexual intercourse.
Catheter associated UTI

• Asymptomatic UTI develop in


catheterized patients after 10-14 days.

• Antibiotic treatment - eradicate


organism but high chance of relapse.

• Catheter removal before treatment is


beneficial.
Antibiotics used in treatment
Sulfamethoxazole-trimethoprim
 Adverse effects: Mechanism of action
o Steven Johnson's syndrome
o Dermatitis
o Angiodema
o GI disturbances
o Agranulocytosis

 Contraindicated in
o Hypersensitivity to sulfa
drugs
o Infants
o Megaloblastic anaemia
nitrofurantoin
 Damages bacterial DNA.
 Reduced to reactive forms by bacterial
nitroreductase- damage DNA, ribosomes

 Adverse effects:
o Hypersensitivity pneumonitis,GI
disturbances, haemolytic anaemia

 Contraindications:
o Renal failure, neonates, pregnancy
Cefixime
 3rd generation cephalosporin
 Disrupts synthesis of peptidoglycan of
bacterial cell wall

 Adverse effects:
o Rash, utricaria
o Diarrhea
o Thrombocytopenia
o leucopenia
Amoxicillin
 Penicillin class antibiotic
 Inhibits cross linking of peptidoglycan
polymer chains which is the major
component of bacterial cell wall.

 Adverse effects:
o Rash
o GI disturbances, renal dysfunction
o Antibiotic associated colitis, lethergy
 Contraindications: penicillin
hypersensitivity
Ciprofloxacin
 Fluoroquinoline antibiotic
 Inhibits DNA gyrase and topisomerase 1V,
the enzymes necessary for separation of
bacterial DNA – inhibit cell division

 Adverse effects:
o Peripheral neuropathy
o Rhabdomyolysis
o Steven Johnson's syndrome
o Hemolytic anaemia
Surgical treatment
a) Surgical removal of renal calculi,
bladder calculi

b) Ureteroplasty

c) Reimplatation of ureters if VUR


present
Conclusion
 Urinary tract infections are the 2nd most
common bacterial infections.
 Women are the most infected subjects in
the population.
 Development of resistance to antibiotics
by the bacteria result in problems during
the treatment and lead to relapse or
recurrence.
 Recent advances such as development of
immunologicals like intranasal vaccines
may result in life time cure of the infection
References
• Clinical pharmacy and therapeutics by
Roger Walker, Clive Edwards; 3rd edition;
page 503 – 511.

• Applied therapeutics the clinical use of


drugs by Mary Anne konda- kimble; 8th
edition; page456 – 465.

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