1. Urinary Tract Infections
Prof. Dr. Çağrı BÜKE
Yeditepe University Medical Faculty
Infectious Diseases and Clinical Microbiology

2. Urinary tract infections (UTIs)
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UTI
Urinary tract infections (UTIs)
A urinary tract infection (UTI) is defined as microbial infiltration of the otherwise sterile urinary tract and is one of the most common bacterial infections world- wide
UTIs encompass infections of the urethra (urethritis), bladder (cystitis), ureters (ureteritis), and kidney (pyelonephritis)

3. Ç. BÜKE
UTI
Epidemiology
UTIs are the most frequent bacterial infection seen in the outpatient setting: 1 in 3 women will develop a UTI requiring antibiotic treatment by age 24, and
UTIs are the second most common cause for prescription of antibiotics
50% experience at least 1 UTI during their lifetime

4. Epidemiology Ç. BÜKE UTI
The incidence of cystitis is significantly higher in women than men, likely the result of anatomic differences
Colonization of the vaginal introitus by gastrointestinal pathogens can also increase the likelihood of urinary tract infiltration
Incidence in men rises dramatically after age 50

5. Epidemiology Ç. BÜKE UTI
Other factors including; urinary tract obstruction, incomplete voiding, and aberrant structural anatomy also predispose individuals to UTIs
Additional risk factors include; prior history of UTIs, vaginal intercourse within the past 2 weeks, use of contraception with spermicide, low vaginal estrogen levels, and individual genetic background

6. Epidemiology Ç. BÜKE UTI Worldwide, 150 million cases / year
90 % cystitis
10 % pyelonephritis
75 % sporadic
25 % recurrent
2 % complicated
The risk of UTI in women increases after menapause
After a UTI 20 – 40% will have a recurrence
UTI is rare in young and middle-aged men
İt often occurs due to catheterisation or urological procedures

7. Definition Ç. BÜKE UTI Bacteriuria; Presence of bacteria in the urine
Significant bacteriuria; Presence of bacteria in the urine ≥ 105 cfu/ml for F and 104 cfu/ml for M
Symptomatic bacteriuria
Asymptomatic bacteriuria
Contamination; Presence of bacteriuria in the urine ≤ 105 cfu/ml or 104 cfu/ml

8. Pathogenesis Ç. BÜKE UTI - Contamination - Colonization
- Invazion of bladder (pili, adhesins)
- Inflammatory response
- Neutrophil infiltration
- Bacterial multiplication
- Biofilm formation
Epitelial damage (by bacterial toxins and proteases
Ascension to the kidney

9. Pathogenesis Ç. BÜKE UTI Inoculum size Virulence Adherence
Ascending route most common 90%
Colonization of urethra and peri-urethral tissue is the initial event
More in woman than man due to short female urethra, so urethral organisms enter bladder in close proximity to perianal areas
Once in the bladder, multiply, then pass up the ureters to the renal pelvis and parenchyma
Hematogenous seeding less frequent 10%

10. Host protective factors in UTIs
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UTI
Host protective factors in UTIs
Mechanical
Dilution and flow of urine
Length of urethra
Interference
Normal bacteria flora (meatus)
Chemical
Osmolality and pH of urine
Prostatic fluid
Anti-adherence mechanisms in bladder
Urinary immunoglobulins
Mucosal antibacterial activity

11. Host factors complicating bacteriuria
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UTI
Host factors complicating bacteriuria
Residual bladder urine after voiding
Turbulent urethral flow (stricture)
Foreign bodies
Stones
Atrophic vaginal mucosa
Vesico-ureteral reflux
Sexual intercourse (insertive rectal sex)
Antibiotics
Spermicides

12. Host factors complicating bacteriuria
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UTI
Host factors complicating bacteriuria
Urinary stasis
Neurologic bladder
Reflux into the ureters (pregnancy)
Obstruction
Congenital anatomical abnormalities
Prostate hypertrophy (age)
Stones, tumor
Diabetes mellitus
Foreign materials
Stones
Stents
Catheters

13. Bacterial virulence factors in UTI
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UTI
Bacterial virulence factors in UTI
E.coli strains expressing O-antigens cause high proportion of infections
Capsular antigens of E.coli associated with clinical severity (antiphagocytic)
P-fimbriae enhance attachment of E.coli to uroepithelial cells
Motile bacteria ascend the ureter against urine flow

14. Bacterial virulence factors in UTI
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UTI
Bacterial virulence factors in UTI
Bacterial urease (Proteus) alkalinizes urine, stone formation and survival of bacteria within stones
Gram (-) endotoxin decreases ureteral peristalsis
Hemolysin damages renal tubular epithelium and promotes invasive infection
Aerobactin of E.coli promote iron accumulation for bacterial replication

15. Types of urinary tract problems
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UTI
Types of urinary tract problems
Asymptomatic bacteriuria
Dysuria
Cystitis
Acute uncomplicated cystitis
Recurrent cystitis
Complicated UTI
Pyelonephritis
UTIs in men, pregnant women, children
Prostatitis
Other
Catheter associated UTI
Candida in urine
Sterile pyuria

16. Clinical symptoms of UTI
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UTI
Clinical symptoms of UTI
Cystitis
Frequency
Dysuria
Urgency
Hematuria
Pyuria (> 10/mm3)
Bacteriuria (≥ 105 cfu/ml F)
(≥ 104 cfu/ml M)

17. Cystitis in male Ç. BÜKE UTI Young men (rare in men under 50)
Anatomic abnormalities
Anal insertive sex, toys
Older men
Calculi
Enlarged prostate (obstruction)
Chronic prostatitis
Organisms differ
E. coli accounts for 40-50%
Proteus and Providencia species accounting for next most frequent cause
Most common cause of relapsing UTI is chronic bacterial prostatitis

18. Clinical symptoms of UTI
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UTI
Clinical symptoms of UTI
Pyelonephritis; Cystitis symptoms +
Fever
Chills
Nausea/vomiting
Costo-vertebral angle tenderness
Leucocytosis , CRP
Pyuria (> 10/mm3)
Bacteriuria (≥ 105 cfu/ml F)
(≥ 104 cfu/ml M)

19. Recurrent UTIs Ç. BÜKE UTI Relapse: same organism in <2 weeks
Suggests uneradicated focus
Ab resistance
Non compliance
Reinfection: may be same or different organism: Interval >2 weeks
Hygiene/wiping
Post-coital
Vaginal atrophy
Post-void residual (prolapse)

20. Complicated urinary tract infection
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UTI
Complicated urinary tract infection
May involve the bladder or kidneys
Symptomatic urinary infection in individuals with functional or structural abnormalities of the urinary tract
Child, male, pregnant female
Kidney involvement, 2nd bacteraemia
Abnormality
Urologic procedure
Catheterization
Unusual or resistant organisms

21. Ç. BÜKE
UTI
Etiology
The most common bacterial cause of uncomplicated community-acquired UTI is uropathogenic Escherichia coli (UPEC), representing >80% of infections
Other pathogens commonly associated with uncomplicated UTI include; Staphylococcus saprophyticus, Klebsiella species, Proteus mirabilis, and Enterococcus faecalis

22. Diagnosis of UTIs Ç. BÜKE UTI History Dysuria – Frequency - Urgency
Vaginitis -no pyuria and <102 cfu/ml)
Candida
Trichomonas
atrophy of vaginal tissues
Urethritis –pyuria and
Chlamydia
Neisseria gonorrhoeae
Cystitis – pyuria and >104-5 cfu/ml, onset abrupt
Pyelonephritis - pyuria and >104-5 cfu/ml,

23. Diagnosis of UTIs Ç. BÜKE UTI Physical examination
Laboratory parameters
Urin sample
In adults, mid stream urine sample usually reliably represents the urine in the bladder
The most reliable sample is obtained via suprapubic puncture
Urine in bladder > 4 hours
Samples from urinary bags or bedpans should not be used as they invariably will be contaminated

24. Diagnosis of UTIs Ç. BÜKE UTI Urinalysis Microscopy Dipstick
Leukocyte esterase: rapid screening test for detecting pyuria
Patients with symptoms and negative LE should have a urine microscopic examination for pyuria
Urinary nitrite
Nitrite is formed when bacteria reduce the nitrate that is normally found in the urine
False negatives common, but false positives are rare

25. Diagnosis of UTIs Ç. BÜKE UTI Quantitative culture
Specialized cultures (TB, fungi)

26. Interpratation of urine culture results
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UTI
Interpratation of urine culture results

27. Asemptomatic bacteriuria
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UTI
Asemptomatic bacteriuria
Positive urine culture repeatedly (105 cfu/ml) in the absence of signs of UTIs
Pyuria does not affect interpretation
Tretment of asemptomatic bacteriuria only in
Pregnant women
Prior to urological invasive procedures
Prevalance varies 1-5% to 100%
Screening for and treatment of asymptomatic bacteriuria is not indicated
Treatment does not prevent further episodes of asemptomatic bacteriuria

28. Asemptomatic bacteriuria
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UTI
Asemptomatic bacteriuria
The risk of pyelonephritis is increased fold during pregnancy
Increased risk for premature delivery and to have low birthweight infants
Treatment of bacteriuria decreases the risks
Screen for bacteriuria by urine culture at least once in early pregnancy and treat for 3-7 days if positive

29. Asemptomatic bacteriuria
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UTI
Asemptomatic bacteriuria
In patients with urinary catheter, antimicrobial therapy not associated with decrease in rate of symptomatic infection
High incidence of recurrence, usually with more resistant organisms
Asymptomatic bacteriuria or funguria should not be screened for or treated in patients with indwelling urethral catheter

30. Treatment of UTIs Ç. BÜKE UTI Acute uncomplicated UTIs (Cystitis)
TMP-SMX (160/800 mg tablet twice daily for 3 days)
> 20% resistance to TMP-SMX
Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days);
1-20% resistance to nitrofurantoin
Fosfomycin trometamol (3 g powder single dose
Amoxicillin (500 mg three times a day)
30% resistance to amoxicillin
Fluoroquinolones (ciprofloxacin 500 mg twice daily) are highly effective in 3-day regimens

31. Treatment of UTIs Ç. BÜKE UTI Acute pyelonephritis
Mild to moderately ill patients
Amox/clav 1 g twice daily
Cefuroxime 500 mg three times a day
Fluoroquinolone: ciprofloxacin, levofloxacin 500 mg once a day
TMP-SMX
Patients usually improve in hours
Treat for 1-2 weeks

32. Treatment of UTIs Ç. BÜKE UTI Acute pyelonephritis
Severely ill patients
Ceftriaxon 1 g twice daily
Floroquinolon
Ampicillin + aminoglycoside
IV therapy until patient afebrile for hours
Treat for 2 weeks
If fever persists and all children and men:
Renal US, CT or MR ± IVP
Look for perinephric abscess
Exclude urinary obstruction

33. Treatment of UTIs in pregnancy
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UTI
Treatment of UTIs in pregnancy
Ampicillin 500 mg three times a day for 7-10 days
Amok/klav 1g twice daily for days
Sefaleksin 250 mg BID-QID for days
Nitrofurantoin mg QID for days

34. Urethritis Ç. BÜKE UTI Neisseria gonorrhoeae Chlamydia Ureoplasma
Antibiotic therapy should cover both gonococcal urethritis and nongonococcal urethritis (NGU)
If concomitant treatment for NGU is not provided, the risk of postgonococcal urethritis is approximately 50%.

35. Urethritis Ç. BÜKE UTI For uncomplicated gonococcal urethritis;
Ceftriaxone, 250 mg IM single dose
For treatment of NGU;
Azithromycin, 1 g orally in a single dose, or
Doxycycline, 100 mg orally twice a day for 7 days
Alternatives;
Erythromycin base 500 mg orally four times a day for 7 days
Levofloxacin 500 mg orally once daily for 7 days

36. Prostatitis Ç. BÜKE UTI Fever, chills Dysuria, pain
Marked local tenderness
Excellent penetration by most antibiotic classes-easily cured
Ciprofloxacin 500 mg twice daily for 6-8 weeks
Levofloxacin 500 mg once a day for 6-8 weeks
TMP-SMX 160/800 mg twice a day for 6-8 weeks

37. Urinary tuberculosis Ç. BÜKE UTI
Hematogenous seeding can occur in cortex and forms granuloma
Seeding in the medulla
In both sites
Granulomas form
Erosion into collecting system
Further spread to ureters, bladder, prostate…
Requires high index of suspicion
Clinical disease insidious
Dysuria, renal functional defects
Key finding is sterile pyuria
PPD skin testing