Module: Pharmacology and Therapeutics III, (Therapeutics part) Coordinator: Dr. Arwa M. Amin Mostafa Academic Level: Undergraduate, B.Pharmacy School: Dubai Pharmacy College Year of first presented in Class: 2018 This presentation is for Educational purpose. It has no commercial value associated with it.

1. URINARY TRACT INFECTIONs
Arwa M. Amin Mostafa
PhD, M.Pharm Clinical Pharm, Dip Mangt, B.Pharm.

2. Arwa M. Amin
WHAT WE WILL DISCUSS TODAY?
• What are Urinary Tract Infections (UTIs)?
• What are the routes of UTIs?
• What is the pathogenesis of UTIs?
• What are the common pathogens of UTIs?
• What are the risk factors of UTIs?
• What are the Clinical Presentations of UTIs?
• How to diagnose UTIs?
• What are the complications of untreated UTIs?
• How to manage UTIs?
• How to prevent UTIs?

3. Arwa M. Amin
URINARY TRACT INFECTIONS (UTIs)
UTIs are infections which affect the Urinary system (Kidneys, Ureters,
Urinary Bladder, Urethra) and adjacent structures (e.g. Prostates).
UTIs include:
Upper UTIs:
• Pyelonephritis
• Infection affecting the Kidneys
Lower UTIs:
• Cystitis
• Infection affecting the Urinary Bladder
• Urethritis
• Infection affecting the Urethra
• Prostatitis
• Infection affecting prostates

4. Arwa M. Amin
URINARY TRACT INFECTIONS (UTIs)
UTIs are infections which affect the Urinary system (Kidneys, Ureters,
Urinary Bladder, Urethra) and adjacent structures (e.g. Prostates).
UTIs include:
Upper UTIs:
• Pyelonephritis
• Infection affecting the Kidneys
Lower UTIs:
• Cystitis
• Infection affecting the Urinary Bladder
• Urethritis
• Infection affecting the Urethra
• Prostatitis
• Infection affecting prostates
Most common UTIs
&
Mostly affecting
women

5. Arwa M. Amin
URINARY TRACT INFECTIONS (UTIs)
• UTIs are commonly caused by Bacterial pathogens.
• Some UTIs are caused by fungal pathogen (but Rare).
• Most UTIs are caused by single organism.
• Hospitalized patients and patients suffering from
predisposing Renal Disease may suffer from
multiorganisms UTI.

6. Arwa M. Amin
PATHOGENESIS OF UTIs
Bacteria may be
seeded in the Kidneys
from blood
Routes of UTIs
Ascending
Bacteria ascends
through the urethra to
the urinary bladder &
multiplies
Hematogenous
Most common route
e.g. E-coli
Less common route
e.g. S. aureus
E-coli: Escherichia coli, S. aureus: Staphylococcus aureus

7. Arwa M. Amin
PATHOGENESIS OF UTIs
• Uropathogen from the bowel
contaminates the periuretheral area
and enter the urethra.
• The pathogen migrates to the urinary
bladder.
• Colonization of the pathogen in the
bladder will cause irritation and
inflammatory reaction.
• Lower UTIs (e.g. Cystitis) may spread to
the kidneys leading to upper UTI such as
Pyelonephritis.
• Upper UTIs may happen also due to
infecting pathogen from blood stream.
UTIs in Women

8. Arwa M. Amin
PATHOGENESIS OF UTIs

9. Arwa M. Amin
COMMON BACTERIAL PATHOGENS OF UTIs
• Escherichia coli G (-)
• Accounts for 80 – 90 % of UTIs
• Klebsiella pneumonia G (-)
• Proteus species G (-)
• Pseudomonas aeruginosa. G (-)
• Coagulase-negative staphylococci (CoNS) (G +)
• Staphylococcus Saprophyticus
• Enterococcus species (G +)
• Staphylococcus aureus (G +)
E. coli
Pseudomonas aeruginosa
Enterococci

10. Arwa M. Amin
RISK FACTORS OF UTIS
• Indwelling urinary catheters
• Urinary catheter may introduce infection
• Bacteria may colonies the catheter
• Woman are at ↑↑ Risk of UTIs
• Risk in Women > Men
• ↑↑ Risk in Pregnant Women
• ↑↑ Risk in sextually active women
• ↑↑ Risk after menopause
• Genetic/Family history
• Immunocompromised patients
• Lack of water intake
• Holding urine
• Use Feminine douches and spray

11. Arwa M. Amin
RISK FACTORS OF UTIS
•Improper Hygiene
•Diabetes Mellitus
•Renal Disease
• Kidney stones
• Abnormal normal flow of urine
• Vesicoureteral reflux
• Chronic Renal Abscess
• Recent Urinary procedure
•Neurological bladder
•Prostatic Hypertrophy

12. Arwa M. Amin
CLINICAL PRESENTATIONS OF UTIs
General Signs and Symptoms for UTIs:
• Painful burning sensation before, during and after urination.
• Lower Abdomenal Pain or Pelvic pain.
• Frequent urination with little urine comes out
• Dysuria
• Persistent urge to Urinate
• Leaks of urine
• Mild Fever
• Fatigue & Malaise
• Presence of blood in urine (Pink/cola color urine)
• Cloudy Urine
• Strong-smelling urine
• Nausea & Vomiting (Not frequent)

13. Arwa M. Amin
SPECIFIC CLINICAL PRESENTATIONS OF EACH UTI
Specific Signs and Symptoms for main UTIs
PyelonephritisUrethritisCystitis
• High Fever with
Chills
• Upper back and
side pain
• Malaise
• Nausea & Vomiting
• Burring with
urination
• Discharge
• Pain in the Bladder
region
• Frequent Urination
• Urgency
• Painful urination
• Lower abdomen
discomfort
• Dark Urine (Blood in
Urine)

14. Arwa M. Amin
UTIS ARE PAINFUL & BURNING … YES, UTI STANDS FOR ….

15. Arwa M. Amin

16. Arwa M. Amin
DIAGNOSIS OF UTIs
Diagnosis
• Depends on detection of the pathogen in presence of UTIs
underlying signs and symptoms.
Laboratory Tests:
• Standard urine analysis
• Urine culture
• Using midstream urine
• Microscopic examination of the urine
• WBCs & RBCs
• Gram stain.
• CBC
• Blood Culture
Other Investigations:
• Ultrasonography
• CT scanCBC: Complete blood count, WBCs: White blood cells, RBCs: Red blood cells, CT: computed tomography scan

17. Arwa M. Amin
DIAGNOSIS OF UTIs
Laboratory Findings of UTIs
• Bacteriuria
• Pyuria (WBC >10/mm3)
• RBCs in urine
• Nitrite-positive urine (with nitrite reducers)
• Indicates nitrite reducing bacteria in the urine (e.g. E. coli)
• Leukocyte esterase-positive urine
• Rapid test to detect pyuria
• Antibody-coated bacteria (ACB)
• An indicator of the site of UTI:
• Present in urine samples of upper UTI (Pyelonephritis)

18. Arwa M. Amin
COMPLICATIONS OF UN-TREATED UTIs
Un-treated UTIs or improperly treated UTIs may lead to serious
complications:
• Recurrence of UTIs (2 or more in 6 months or 4 or more in one
year)
• Permanent kidney damage from pyelonephritis.
• High risk of early delivery in pregnant ladies (Premature infant or
low weight infant).
• Urethral narrowing in men.
• Prostatitis.
• Urosepsis.
• Sepsis
• Spread of the infection to the blood stream.
• Sepsis is Life threatening condition

19. Arwa M. Amin
MANAGEMENT OF UTIs
Goals of UTIs Therapy:
To provide symptomatic and supportive treatment.
To eradicate pathogenic infection.
To prevent and treat recurrence.
To Identify and treat predisposing risk factors.
Symptomatic and supportive treatment:
• Drinking plenty of Water to increase the frequency of emptying the urinary
bladder.
• Encourage frequent emptying of urinary bladder.
• Antipyretic if fever present.
• Urinary Analgesic if burning and urinary pain are present: Phenazopyridine

20. Arwa M. Amin
MANAGEMENT OF UTIS
Systematic Approach to Manage UTIs
Management of UTIs includes the following steps:
Initial Evaluation of the UTI and patient’s condition.
Selection of Antimicrobial agent & duration of Therapy based on:
Severity of signs & symptoms
Site of infection; upper UTI or lower UTI?
Categorizing UTI type: Complicated or un-complicated?
Microorganism is drug sensitive or drug resistant
Selection of AB should be based on Local resistance rates of E. coli
Follow-up Evaluation.

21. Arwa M. Amin
MANAGEMENT OF UTIS
Categorization of UTIs for proper Antimicrobial selection
• Proper Management of UTIs is achieved by categorizing the UTI in
one of six UTIs categorizes
Acute Un-complicated
Cystitis
Symptomatic Abacteriuria
(Urethral Syndrome)
Asymptomatic Bacteriuria
Recurrent Infections
Prostatitis
Complicated UTIs

22. Arwa M. Amin
MANAGEMENT OF UTIS
Asymptomatic Bacteriuria
• Transient and resolves without AB treatment.
• Can resolve within one week
• Treat with AB if Pregnant woman.
Symptomatic Abacteriuria (Urethral Syndrome)
• Symptomatic & supportive treatment
• Some studies showed that AB is effective.
• As Urethral Syndrome can be due to Low Estrogen, it can be treated
with hormonal replacement.

23. Arwa M. Amin
MANAGEMENT OF UTIs
• Cephalosporins
• Ceftriaxone, Cephalexin,
Ceftazidime, Cefepime
• Cephalexin active against E. coli,
Proteus & Kelibsella
• Penecillins
• Amoxicillin-clavulanates
• Ampicillin-sulbactam
• Aminoglycosides
• Gentamicin, Tobramycin &
Amikacin
• Adjust dose for renal impairment
Commonly used Antimicrobials for UTIs:
• Nitrofurantoin
• Most active antimicrobial against E.
coli.
• Avoid if CrCl < 30 mL/min
• Doesn’t cover Proteus infections
• Trimethoprim-sulfamethoxazole
• Don’t use if resistance is suspected
• Renal dose adjustment and Avoid if
CrCl < 15 mL/min
• Fluoroquinolones
• Ciprofloxacin, Levofloxacin
• Fosfomycin
• Active against E. coli &
Enterococcus
CrCl: Creatinine Clearance

24. Arwa M. Amin
MANAGEMENT OF UTIs
Empiric Antimicrobial Therapy for UTIs
Antimicrobial TreatmentType of UTI
1st line:
Nitrofurantoin: 100 mg PO, BID for 5 days Or
Trimethoprim-sulfamethoxazole: 160/800 mg DS PO bid for 3 days
Fosfomycin: 3 g, OD, for 1 day
2nd line: (particularly, if Pyelonephritis is suspected):
Fluoroquinolones: Ciprofloxacin 250 mg PO, BID for 3 days or
Levofloxacin 250 mg PO, OD for 3 days
Acute
uncomplicated
Cystitis
Ceftriaxone 250 mg IM + either Azithromycin 1 g PO once Or
doxycycline 100 mg PO BID for 7 days
Urethritis
Long-term Prophylaxis:
Nitrofurantoin: 50 mg PO, OD for 6 months Or
Trimethoprim-sulfamethoxazole: ½ (80/400 mg) SS PO OD for 6
months
Recurrent
Infections
(Prophylaxis)
DS: double strength, SS: single strength

25. Arwa M. Amin
MANAGEMENT OF UTIs
Empiric Antimicrobial Therapy for UTIs
Antimicrobial TreatmentType of UTI
1st line:
Fluoroquinolones: Ciprofloxacin 500 mg PO, BID Or
Levofloxacin 250 mg PO, OD, for 7-10 days
2nd line:
Trimethoprim-sulfamethoxazole: 160/800 mg DS PO bid for 14 days
Acute un-
complicated
Pyelonephritis
Amoxicillin-Clavulanate: 500/125mg, TID, for 14 days
Fluoroquinolones: Ciprofloxacin 500 mg PO, BID Or
Levofloxacin 250 mg PO, OD, for 7-10 days or
Aminoglycosides: Gentamicin 7.5mg/kg IV q24h (adjust dose based
on renal function)
In serious cases patient may require hospitalization & IV treatment
Acute
complicated
Pyelonephritis
Trimethoprim-sulfamethoxazole: 160/800 mg po BID for 4-6 weeks
Fluoroquinolones: Ciprofloxacin 500 mg PO, BID, 4-6 weeks
Prostatitis

26. Arwa M. Amin
MANAGEMENT OF UTIS IN PREGNANCY
• UTI during Pregnancy should be treated to avoid UTIs
complications in Pregnancy.
• AB should be with Minimum adverse effect
• AB can be used for 7 days treatment course:
• Cephalexin
• Amoxicillin
• Amoxicillin-Clavulanate
• Contraindicated UTI AB during Pregnancy:
• Tetracyclines, why?
• Teratogenic
• Sulfonamides; particularly in the 3rd trimester, why?
• Possible development of Hyperbilirubinemia & Kernicterus
• Fluoroquinolones, why?
• They may inhibit cartilage & bone development in Newborns

27. Arwa M. Amin
MANAGEMENT OF UTIS IN CHILDREN
• The recommended initial ABs for children with UTIs** are as the following
for 3 or 5 days course:
• Trimethoprim/sulfamethoxazole 6-12 mg/kg/day, divided q 12 h
• Contraindicated in infants < 6 weeks
• Alternative ABs
• Amoxicillin/clavulanate (particularly if acute pyelonephritis is diagnosed).
• 20-40 mg/kg/day divided q 8 h
• Cephalosporins, such as
• Cephalexin 50-100 mg/kg/day divided q 6 h Or
• Cefixime 8 mg/kg/day divided q 24 h
**Note: Nitrofurantoin 5-7 mg/kg/day PO divided q 6 h can be
used, however it is contraindicated in infants < 3 months

28. Arwa M. Amin
MANAGEMENT OF UTIS IN CATHETERIZED PATIENTS
Asymptomatic Bacteriuria in short-term catheterized patient (<30
days):
• Remove the catheter as soon as possible
• Don’t provide AB
Symptomatic Bacteriuria:
• Remove the catheter
• Treat as complicated UTIs
It is NOT recommended to routinely use Prophylactic AB therapy to
prevent UTIs in catheterized patients.
• It may lead to emergence of resistant organisms.

29. Arwa M. Amin
PREVENTING UTIs in Adults
• Drinking plenty amounts of water daily.
• Drinking water will ↑↑ urination which will help to flush
bacteria before causing infection.
• Don’t Hold
• Urinate as soon as needed.
• Proper Hygiene.
• Taking shower is better than taking tube bath.
• Wipe from front to back after urination, particularly
women.

30. Arwa M. Amin
PREVENTING UTIs in Adults
• Avoid using irritating feminine douches and sprays.
• Drink un-sweetened Cranberry juice.
• Using Lactobacillus probiotics
• It helps in ↓↓ vaginal pH → ↓↓ E. coli colonization
• Wear Loose clothes to promote air-circulation.

31. Arwa M. Amin
PREVENTING UTIs
• The American College of Obstetrics and Gynecology
suggested that Cranberry Un-sweetened Juice &
Cranberry Supplements may help to prevent UTIs.
• The dose and duration of using Cranberries for UTI prevention
are nor yet well established.
• Suggested Mechanism of action:
• Cranberries acidifies urine making it unfriendly environment
for E. coli.
• Cranberries prevent bacteria from sticking to the wall of UT.
Cranberry Un-sweetened Juice

32. Arwa M. Amin
PREVENTING UTIs
Limitations of using Cranberries Supplements for UTI
prevention:
• Contains ↑↑ Oxalate salts; they may lead to kidney stones
formation in susceptible people.
• Drug-Interactions with warfarin → bleeding
Cranberry Un-sweetened Juice

33. Arwa M. Amin
PREVENTING
UTIs in
Children
Figure source: How to Treat and Prevent Urinary
Tract Infections (UTIs) in Children,
https://www.top10homeremedies.com/how-
to/how-to-treat-and-prevent-urinary-tract-
infections-utis-in-children.html

34. Arwa M. Amin