The pathogenic track to urinary tract

1. The pathogenic track to urinary tract

2. ShadiZiaie Board of clinical pharmacy Assistant professor of SBMU Labbafinejad Hospital Urinary Tract Infection(UTI)

3. Definition • Significant bacteriuria in presence of symptoms at any level of urinary tract - Bladder: cystitis - Urethra: urethritis - Renal pelvis: pyelitis - Renal parenchyma: pyelonephritis

4. Urinary Tract Infection • Upper urinary tract Infections • Pyelonephritis • Lower urinary tract infections • Cystitis(traditional UTI) • Urethritis(often sexually-transmitted) • Prostatitis

5. Epidemiology Worldwide, 150 million cases / year 90 % cystitis 10 % pyelonephritis 75 % sporadic 25 % recurrent 2 % complicated

6. 25-35% of women between ages of 20 - 40 years • 30 times more likely in young women than young men • Incidence after age 65 same in men and women

7. Prevalence • Almost half of all women will have at least one UTI in their lives. • The risk of UTI in women increases after menopause • After a UTI: 20 - 40 % will have a recurrence • Recurring infections are usually reinfections. • Asymptomatic bacteriuria in women ↑with age & occurs in 2.7% of 15 - 24 year olds 9.3% of over 65 year olds 20 - 50% of over 80 year olds

8. UTI is rare in young and middle-aged men • Often with catheterisation or urological procedures. • Bacteriuria in elderly men occurs in • 10% of those living at home, • 20% of those living in nursing homes • 30% of those who are in hospitals • Urinary catheter increases the risk almost ten-fold in hospitalised patients and those in other care homes. • Pyelonephritis is common in patients who have been catheterised for over a month.

9. Infant and children : Male >> female Adolescent-menopause : Female >> male Older age : Female = = male Women: Short ureter Sexual contact : Colonization of pathogens in bladder Spermicidal : Change of normal flora Men (<50) : Prostate infection, anatomical defects , Lack of circumcision, homosexuals

10. Risk Factors • Obstruction ,congenital, stones • Reflux • Retention • Diabetes Mellitus • Age • Alteration of vaginal flora : antibiotics, spermicide • Insertive rectal intercourse

11. Predisposing Factors • Prostatic hypertrophy • Urethral strictures • Calculi • Tumors • Bladder diverticula • Anticholinergic drugs • Neurologic malfunctions associated with stroke • Diabetes • Spinal cord injuries • Other neuropathies • Conditions resulting in residual urine volumes:

12. Complicated or Un-Complicated UTI • UncomplicatedUTI is the one occurring in a healthy young nonpregnant woman. • Complicated UTI is the one occurring in anyone else.

13. Etiology • Bacteria causing UTIs usually originate from host bowel flora • Virtually every organism associated with UTIs • Certain organisms predominate due to specific virulence factors • Escherichia coli • Most common cause of uncomplicated UTIs • 85% of community-acquired infections

14. Etiology • Additional causative organisms in uncomplicated infections • Staphylococcus saprophyticus (5% to 15%) • Klebsiella pneumoniae • Proteus spp. • Pseudomonas aeruginosa • Enterococcus spp. (5% to 10%)

15. Etiology • Other frequently isolated organisms in complicated infections • Proteus spp. • K. pneumoniae • Enterobacter spp. • P. aeruginosa • Staphylococci • Enterococci

16. Complicated infections • Enterococci • 2nd most frequently isolated organisms in hospitalized patients • May be related to extensive 3rd generation cephalosporin use, not active against enterococci • Vancomycin-resistant Enterococcus faecalis and Enterococcus faecium • Widespread, major therapeutic and infection control issues • Especially long-term hospitalization or underlying malignancy • Susceptible to few antimicrobials

17. Staphylococcus aureus infections • May arise from urinary tract • More commonly from bacteremia producing metastatic abscesses in the kidney • Candida spp. common cause of UTI in critically ill and chronically catheterized patient • Most UTIs caused by single organism • Multiple organisms isolated in certain patients • Stones, indwelling urinary catheters, chronic renal abscesses • May represent contamination; repeat evaluation

18. Pathogenesis • Bacterial Invasion • Ascending route 95% • Hematogenous • Lymphatic • Ascending route via the urethra • Men longer urethra/prostatic secretions • Women shorter urethra/colonization • Chance of infection increased by obstruction or foreign body

19. Pathogenesis • After bacteria enter the urinary tract, infection depends on • Bacteria virulence • Size of inoculum • Host defenses

20. Host defenses • Bacterial Adherence plays major role in bacteria infectivity • Anti-adherence mechanisms include • Interference by normal bacteria flora • Urinary immunoglobulins • Muco and oligosaccharides may block binding • Mechanical - dilution and flushing • Under normal circumstances, urine inhibits and kills microorganisms • Low pH, osmolality extremes • High urea concentration • High organic acid concentration

21. Patients unable to void urine completely • Greater risk for UTIs • Recurrent infections common • Even small residual amounts of urine in bladder causes less favorable treatment response • Additional host factors may play role in UTI prevention • Lactobacillus in vaginal flora • Produce lactic acid • Help maintain low vaginal pH preventing vaginal E. coli • Circulating estrogen • Supports vaginal lactobacilli in premenopausal women

22. Decreases in lactobacilli colonization? • Spermicides • β-lactam antimicrobials • Lower estrogen levels • Intercourse with new partner • Douching

23. Clinical Presentation

24. Clinical Presentation • Elderly patients often have nonspecific symptoms • Altered mental status • Change in eating habits • Gastrointestinal symptoms • Patients with indwelling catheters or neurologic disorders commonly do not have lower tract symptoms • May have flank pain and fever • May develop upper tract infections with bacteremia and no/minimal urinary tract symptoms

25. Urine Collection • Midstream clean-catch method • Preferred for routine collection • Clean urethral opening area • Void and discard 20 to 30 mL • Collect next part of urine flow • Process immediately • Refrigerate as soon as possible • Specimens at room temperature for several hours may have falsely elevated bacterial counts

26. Urine Collection • Catheterization ? • Uncooperative patients • Patients unable to void urine • Results reliable with careful aseptic technique • May introduce bacteria into bladder • Associated with infection in 1% to 2% of patients

27. Bacterial Count UTI diagnosis is based on significant numbers of bacteria in urine Historically, bacterial counts equal to or greater than 100,000 organisms/mL of urine in a "clean-catch" specimen were judged to indicate true infection. Counts less than 100,000 organisms/mL of urine, however, may represent true infection in certain situations: with concurrent antibacterial drug administration, rapid urine flow, low urinary pH, or upper tract obstruction.

28. Significant bacteriuria

29. Pyuria • White blood cell (WBC) count >10 WBC/mm3 of urine • Pyuria in symptomatic patients correlates with significant bacteriuria • Nonspecific • Presence of inflammation • Not necessarily infection • Sterile pyuria associated with urinary tuberculosis, chlamydial, fungal urinary infections

30. Hematuria and Proteinuria • Hematuria • Microscopic or gross • Common in UTI patients • Nonspecific • May indicate other disorders • Renal calculi • Tumors • Glomerulonephritis • Proteinuria common with infection

31. Chemistry • Common dipstick test • Detects nitrite formed by nitrate reducing bacteria • False-positives uncommon • False-negatives more common; bacteria do not reduce nitrate • Gram-positive organisms • P. aeruginosa  • False test caused by • Low urinary pH • Frequent voiding • Dilute urine

32. Culture • Most reliable diagnostic method, “gold standard” • Bladder urine normally sterile • Differentiate contamination from infection by quantifying number of bacteria in urine sample • Determine organism susceptibility after identification and quantification • Select agent for treatment • Bacterial susceptibility • Achievable antibiotic urine concentration

33. Management • Nonspecific therapies in UTI treatment and prevention • Fluid hydration: rapid dilution of bacteria and removal of infected urine by increased voiding • Critical factor: residual volume after voiding • As little as 10 mL of residual urine can significantly alter eradication of infection • Paradoxically, increased diuresis may promote susceptibility to infection by diluting normal antibacterial properties of urine

34. Large volumes of cranberry juice increase antibacterial activity of urine and prevent UTIs • Fructose and other unknown substances (condensed tannins) interfere with pathogen adherence mechanisms • Urine acidification does not appear to play significant role • Acidifying urine with systemic agents not recommended

35. Urinary analgesics such as phenazopyridine HCl used by many clinicians • Pain/dysuria are consequence of infection • Urinary analgesics have little clinical role • Most symptoms respond rapidly to antibiotics • Urinary analgesics may mask signs/symptoms of UTIs not responding to antimicrobials

36. Lactobacillus probiotics • May aid in preventing female UTIs • Lowers vaginal pH which decreases E. coli colonization • Topical estrogen replacement may help prevent recurrent UTIs in postmenopausal women • Decreases vaginal Lactobacillus • Decreases pH and E. coli colonization

37. Pharmacologic Therapy • Ideal antimicrobial agent • Well tolerated • Well absorbed • High urinary concentrations • Spectrum of activity limited to known or suspected pathogen(s)

38. Pharmacologic Therapy • Categorize type of infection • Acute uncomplicated cystitis • Symptomatic abacteriuria • Asymptomatic bacteriuria • Complicated UTI • Recurrent infection • Prostatitis • Antibiotic choice based on geographic resistance patterns and patient's recent antibiotic exposure

39. Acute Uncomplicated Cystitis • Most common form of UTI • typically women of childbearing age • often related to sexual activity • Predominantly E. coli • Other causes: S. saprophyticus, K. pneumoniae, Proteus mirabilis • Many clinicians advocate cost-effective management • urinalysis • empirical therapy without urine culture

40. Symptomatic Abacteriuria • Symptomatic abacteriuria: acute urethral syndrome • Females present with dysuria and pyuria • Urine culture reveals < 105 bacteria/mL of urine • >50% of dysuria complaints • Most patients with pyuria have infection that requires treatment • Trimethoprim-sulfamethoxazole single-dose or short-course effective • Prolonged courses not necessary for most patients • Obtain culture if single-dose or short-course therapy ineffective

41. Symptomatic Abacteriuria • Recent sexual activity: consider therapy for C. trachomatis  • 1 g azithromycin  • Doxycycline 100 mg BID for 7 days • Treatment of sexual partners often required

42. Asymptomatic Bacteriuria • 2 consecutive urine cultures with > 105 organisms/mL of same organism without urinary symptoms • Most patients elderly or pregnant women • Patients typically respond to treatment; however, relapse and reinfection common • Chronic asymptomatic bacteriuria difficult to eradicate

43. Asymptomatic Bacteriuria • Management depends on age and whether patient is pregnant • Children • Greater risk of renal scarring/long-standing renal damage • Treat with conventional therapy for symptomatic infection • Greatest risk of renal damage at ages < 5 years

44. Complicated UTI

45. Acute Pyelonephritis • Treat high-grade fever (> 38.3°C) and severe flank pain as acute pyelonephritis • Manage aggressively • Hospitalize severely ill patients • nausea, vomiting, dehydration • IV antimicrobials initially • Milder cases managed outpatient with PO antibiotics

46. Acute Pyelonephritis • Agents of choice: trimethoprim-sulfamethoxazole, fluoroquinolones • If Gram stain reveals gram-positive cocci, consider Streptococcus faecalis  • Direct treatment against this potential pathogen  (ampicillin) • Close follow-up mandatory to ensure success

47. Acute Pyelonephritis • Empirical antibiotic regimens • IV fluoroquinolone • aminoglycoside + ampicillin • extended-spectrum cephalosporins + aminoglycoside • aztreonam • β-lactamase inhibitor combinations • ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin-tazobactam • carbapenems • imipenem, meropenem, ertapenem • IV trimethoprim-sulfamethoxazole

48. Acute Pyelonephritis • Consider P. aeruginosa, enterococci, multiply resistant organisms if patient hospitalized within past 6 months, urinary catheter, nursing home resident • Treatment recommendations • ceftazidime • ticarcillin-clavulanate • Piperacillin • Aztreonam • Meropenem • Imipenem + aminoglycoside

49. Acute Pyelonephritis • 3 days aminoglycoside combination therapy followed by nonaminoglycoside single-agent therapy for 7 days: 100% cure rate in experimental animals • Effective therapy should stabilize patient within 12 to 24 hours • significant reduction in urine bacterial concentrations within 48 hours • consider alternative agent based on susceptibility if inadequate bacteriologic response • If patient fails to respond in 3 to 4 days or has persistently positive blood or urine cultures, exclude • bacterial resistance • possible obstruction • papillary necrosis • intrarenal or perinephric abscess • other disease process

50. UTIs in Males • Often more difficult to manage than in females • Incidence of infection in males < 60 years much less than in females • Infection related to urinary tract manipulation • urinary tract instrumentation • catheterization • renal and urinary stones • Conventional view: males require prolonged treatment • Obtain urine culture before treatment • Cause not as predictable as in women