Urinary Tract Infections

1. Urinary Tract Infections Meral Sönmezoğlu Division of Infectious Diseases Yeditepe University Hospital

2. Learning objectives UTI’s • Epidemiology • Pathogenesis • Risk Factors • Types of cystitis • Evaluation • Therapy

5. Epidemiology UTI’s • UTIs are the second most common cause for prescription of antibiotics • Most infections are limited to the lower urinary tract • 30 times more likely in young women than young men • Incidence in men rises dramatically after age 50

6. Relative frequency of nosocomial (hospital-acquired) infections

7. Pathogenesis UTI’s Bacteria travel: • Ascending route via the urethra 95% • Hematogenous (kidney-> bladder) • Endocarditis • Tuberculosis • Direct (connection bowel-bladder)

8. Bacterial factors • Inoculum size • Virulence • Adherence • E. coli adhere to urothelial cells • Proteus, Providencia adhere to lumen of catheter material

9. Virulence Host factors Infection No infection

10. Host defense mechanisms • 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. Risk factors UTI’s (I) • Alteration/introduction of bacteria • Antibiotics • Spermicides • Vaginal atrophy (age) • Sex • Insertive rectal sex • Inserting toys • Patient education: • Void after intercourse, • Proper wiping, front to back once

12. Urinary stasis Neurologic bladder Reflux into the ureters (pregnancy) Obstruction Congenital anatomical abnormalities Prostate hypertrophy (age) Stones, tumor Diabetes mellitus Glycosuria Foreign materials Stones Stents Catheters Risk factors UTI’s (II)

13. Pathogenesis of cystitis

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

15. Definitions (I) • Asymptomatic bacteriuria: • isolation of a specified quantitative count of bacteria • in an appropriately collected urine specimen • obtained from a person without symptoms or signs referable to urinary infection • Acute uncomplicated UTI (cystitis): • symptomatic bladder infection • characterized by frequency, urgency, dysuria or suprapubic pain • in a woman with a normal genitourinary tract

16. Definitions (II) • Acute nonobstructive pyelonephritis: • renal infection • characterized by costovertebral angle pain • often with fever • sometimes with bacteraemia • Complicated urinary tract infection: • may involve the bladder or kidneys • symptomatic urinary infection • in individuals with functional or structural abnormalities of the urinary tract

17. What can the laboratory do with a sample of urine? • Urinalysis • Microscopy • Dipstick • Quantitative culture • Specialized cultures (TB, fungi)

18. Urine 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

19. Urinary tract organism quantification • Bladder urine is sterile • Distal urethra is not sterile • How can we differentiate: • bladder bacteria (pathogens) from • urethral bacteria (contaminants)?

20. What is a positive culture? • Classic definition: > 105 cfu/ml • With symptoms: > 103 cfu/ml • 90% chance of actual infection

21. Microscopy • A true UTI is accompanied by • Pyuria • >10 leukocytes/mm³ of uncentrifuged urine • unless catheter in place • Lack of epithelial cells • >5/ mm³ indicates contamination • Only one bacterial species (monoculture) • >105 cfu • Do not culture urine unless • Indicated AND • Abnormal UA

22. Dysuria • Dysuria can be caused by • Vaginitis -no pyuria and <102 cfu/ml) • Candida • Trichomonas • atrophy of vaginal tissues • Urethritis –pyuria and <102 cfu/ml, gradual • Chlamydia • Neisseria gonorrhoeae • Cystitis – pyuria and >103 cfu/ml, onset abrupt

23. Asymptomatic bacteriuria - why screen? • Screening of asymptomatic people for bacteriuria is only appropriate to prevent adverse events • In pregnancy (Gp B strep) • Prior to urologic surgery • Undesirable outcomes associated with therapy: • Antimicrobial resistance • Adverse drug effects • Costs • C. difficile associated disease

24. Asymptomatic bacteriuria-Healthy, premenopausal women • Bacteriuria increases risk for symptomatic UTI • Not associated adverse outcomes • Treatment of asymptomatic bacteriuria • neither decreases frequency of symptomatic infection • nor prevents further episodes of asymptomatic bacteriuria • Screening for and treatment of asymptomatic bacteriuria is not indicated

25. Asymptomatic bacteriuria - Pregnant women • 20-30 fold increased risk of pyelonephritis during pregnancy • More likely to experience premature delivery and to have low birthweight infants • Treatment of bacteriuria decreases above risks • Screen for bacteriuria by urine culture at least once in early pregnancy and treat for 3-7 days if positive

26. Asymptomatic bacteriuria -Elderly institutionalized subjects • No decrease in rate of • symptomatic infection • improvement in survival • chronic GU symptoms with Abx therapy • Screening and treatment of asymptomatic bacteriuria in elderly institutionalized residents of long-term care facilities not recommended

27. Asymptomatic bacteriuria –Patients with indwelling catheters • 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

28. Symptoms Dysuria, frequency, urgency Initial and terminal hematuria Suprapubic discomfort Low-grade fever may occur Exclude other causes STD Vaginitis Diagnosis Dipstick or microscopy Nitrite positive Positive LE/WBC (>10 WBC’s) Culture Not routinely necessary Carefully obtained clean catch 104-5 cfu/ml 1 bacterial species only Acute uncomplicated UTI (cystitis)

29. Acute uncomplicated UTI (cystitis) • Bacteria • E. coli in 80-90% • Staph. saprophyticus in 5-15% • Proteus and Klebsiella species • Adult female • No anatomic/functional/immunologic abnormalities • Non-pregnant

30. Acute uncomplicated UTI -Therapy • Resistance varies • 30% resistant to amoxicillin • 1-20% to nitrofurantoin • 5-15% to TMP-SMX • Recommend: course of • TMP-SMX as first choice (3 days) • Fluoroquinolone as second (3 days) • Nitrofurantoin (7 days) • Does not penetrate in kidney

31. IDSA guideline • TMP-SMX (160/800 mg tablet twice daily for 3 days) • Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days); • Fosfomycin trometamol (3 g powder single dose • Pivmecillinam (400 mg bid for 3–7 days • Fluoroquinolones are highly effective in 3-day regimens

32. Other treatment – non antimicrobial • Acidification • Acid urine is antibacterial • Cranberry juice has precursors to hippuric acid and so acidifies urine BUT • Have to avoid diet that alkalizes urine – milk, fruit juice • Acid can precipitate stones in the urine (oxalic acid stones from ascorbic acid intake)

33. Recurrent Cystitis • Relapse: same organism in <2 weeks • Suggests uneradicated focus • Abx resistance • Non compliance • Reinfection - may be same or different organism: Interval >2 weeks • Hygiene/wiping • Post-coital • Vaginal atrophy • Post-void residual (prolapse)

34. Complicated UTI • Child, male, pregnant female • Kidney involvement, 2nd bacteraemia • Abnormality • Anatomy, function, immunology • Urologic procedure • Catheterization • Unusual or resistant organisms

35. Acute pyelonephritis • Usually E. coli • Obtain urine culture • If hospitalized obtain blood cultures • Mostly an ascending infection • Disease severity • Mild • Life threatening urosepsis

36. Acute pyelonephritis -Therapy • Mild to moderately ill patients • TMP-SMX (bactrim) amox/clav, cefuroxime or fluoroquinolone • Patients usually improve in 48-72 hours • Treat for 1-2 weeks • Severely ill patients • Ampicillin + aminoglycoside • IV therapy until patient afebrile for 48-72 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

37. Management: UTI in Pregnancy • Nitrofurantoin 50-100mg QID X 7- 10 days • Amok/klav 250mg QID X 7- 10 days • Sefaleksin250 mg BID-QID X 7- 10 days

38. Complicated UTI: • > 2 UTI’s / year • Antibiotic resistance • Any UTI in a male.

39. Cystitis in males • 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

40. UTI’s in males (other than pyelonephritis) • Urethritis (STI’s) • Gonorrhea • Chlamydia • Ureoplasma • Prostatitis • Same organisms as above • For older males (in addition to above): • Gram negative rods • Enterococci

41. Acute prostatitis • Fever, chills • Dysuria, pain • Marked local tenderness • Excellent penetration by most antibiotic classes-easily cured • Complications • Prostatic abscess • Chronic prostatitis

42. Chronic prostatitis • Chronic pain • Dysuria • Recurrent “UTI’s” – same organism • Poor antibiotic penetration-difficult to treat • Biofilm • Calculi • Preferred agents • Fluoroquinolones • TMP-SMX

43. Role of the catheter in UTI • Conduit • Internal lumen • Migration of bacteria along external surface • Foreign body • Biofilm formation • Protects from host defense • Protects from antibiotics • Incomplete emptying

44. Situations When a Urinary Catheter is Used • A urinary catheter is used in many different situations: • A urinary catheter may be inserted to drain the bladder before or during a surgical procedure, during recovery from a serious illness or injury, or to collect urine for testing • A urinary catheter may be used for a person who is incontinent of urine, if the person has wounds or pressure ulcers that would be made worse by contact with urine • A urinary catheter is necessary when a person is unable to urinate because of an obstruction in the urethra

45. Types of catheters • A condom catheter, consists of a soft plastic or rubber sheath, tubing, and a collection bag for the urine. The sheath is placed over the penis and the collection bag is attached to the leg. Collects urine when there is no need for catheter insertion. • A straight catheter, is used when the catheter is to be inserted and removed immediately. • An indwelling catheter, also known as Foley catheter, is left inside the bladder to provide continuous urine drainage. • A suprapubic catheter is a type of indwelling catheter. The suprapubic catheter is inserted into the bladder through a surgical incision made in the abdominal wall, right above the pubic bone. • A 3-way catheter for continuous bladder irrigation (CBI) is a type of indwelling catheter. It is inserted to irrigate the bladder to prevent obstruction (i.e bleeding)

46. Catheters Straight Condom Indwelling Suprapubic

47. Genitourinary tuberculosis From: Johnson and Feehally, Comprehensive Clinical Nephrology, 2000, Elsevier

48. Genitourinary tuberculosis • Hematogenous seeding can occur in cortex and forms granuloma • Seeding in the medulla • In both sites • Granulomas form • Caseation • Erosion into collecting system • Further spread to ureters, bladder, prostate…

49. Genitourinary tuberculosis • Requires high index of suspicion • Clinical disease insidious • Dysuria, renal functional defects • Key finding is sterile pyuria • PPD skin testing • Culture M. tuberculosis from urine • Early AM sample (urine concentrated) • Multiple urine samples • Imaging

50. Community-Acquired UTI E.coli S.epi & gm - enterics Enterococcus Proteus S.saprophyticus K.pneumoniae