Infections of the Upper Urinary Tract

1. Infections of the Upper Urinary Tract

2. Bacteriuria is the presence of bacteria in the urine. Bacteriuria may be asymptomatic or symptomatic. • Bacteriuria without pyuria indicates the presence of bacterial colonization of the urine, rather than the presence of active infection

3. Pyuria is the presence of white blood cells in the urine (implying an inflammatory response of the urothelium to bacterial infection • In the absence of bacteriuria, some other pathology such as carcinoma in situ, TB infection, bladder stones, or other inflammatory conditions). • An uncomplicated UTI is one occurring in a patient with a structurally and functionally normal urinary tract • Complicated UTI is one occurring in the presence of an underlying anatomical or functional abnormality

4. Isolated UTI: an interval of at least 6 months between infections • Recurrent UTI: >2 infections in 6 months, or 3 within 12 months.Recurrent UTI may be due to reinfection

5. INCIDENCE AND EPIDEMIOLOGY • Most common bacterial infection • .2% of all office visits by women and 0.6% of all office visits by men • Overall prevalence of bacteriuria in women has been estimated at 3.5% • 30% of women will have had a symptomatic UTI requiring antimicrobial therapy by age 24 • 30% of women will have had a symptomatic UTI requiring antimicrobial therapy by age 24

6. Incidence of bacteriuria also increases with institutionalization or hospitalization and concurrent disease • 57% to 80% of bacteriuric women who are untreated or treated with placebo clear their infections spontaneously • Once a patient has an infection, he or she is likely to develop subsequent infections.

7. If antimicrobial prophylaxis is started after the second or any succeeding infection within a set, about one third of the women will be treated unnecessarily • If antimicrobial prophylaxis is started after the second or any succeeding infection within a set, about one third of the women will be treated unnecessarily • Whether a patient receives no treatment at all, or short-term, long-term, or prophylactic antimicrobial treatment, the risk of recurrent bacteriuria remains the same

8. Prophylactic antimicrobial therapy reduces reinfections but does not alter the underlying predisposition to recurring infection • Studies suggest that it makes little difference whether a UTI is cured with an antimicrobial agent or is allowed to clear spontaneously—the susceptibility to recurrent UTI remains the same • sequelae of complicated UTIs are substantial • presence of obstruction, infection stones, diabetes mellitus, and other risk factors

9. Factors That Suggest Complicated UTI • Functional or anatomic abnormality of urinary tract    • Male gender    • Pregnancy   • Elderly/  Diabetics/   Immunosuppression    • Childhood UTI/   Recent antimicrobial agent    • Indwelling urinary catheter   Urinary tract instrumentation   Hospital-acquired infection   Symptoms for more than 7 days at presentation

10. PATHOGENESIS • Interactions between the uropathogen and the host • Successful infection of the urinary tract is determined in part by the • virulence factors of the bacteria • the inoculum size • inadequacy of host defense mechanisms • These factors also play a role in determining the ultimate level of colonization and damage to the urinary tract

11. Routes of Infection • Ascending Route • Hematogenous Route • Lymphatic Route

12. Urinary Pathogens • Most UTIs are caused by facultative anaerobes usually originating from the bowel flora • Staphylococcus epidermidis and Candida albicans originate from the flora of the vagina or perineal skin • E.coli is by far the most common cause of UTIs, accounting for 85% of community-acquired and 50% of hospital-acquired infections • Enterobacteriaceae, including Proteus and Klebsiella, and gram positive E. faecalis and S. saprophyticus

13. The prevalence of infecting organisms is influenced by the patient's age

14. Fastidious Organisms • Anaerobes in the Urinary Tract • uncommon • Distal urethra, perineum, and vagina • normally colonized by anaerobe • 1% to 10% of voided urine specimens are positive for anaerobic organisms

15. Anaerobic organisms are frequently found in suppurative infections of the genitourinary tract. • found during evaluation for sterile pyuria

16. Chlamydia • not routinely grown in aerobic culture but have been implicated in genitourinary infections.

17. Bacterial Virulence Factors • Virulence characteristics play a role in determining both if an organism will invade the urinary tract and the subsequent level of infection • The expression of virulence factors that enable them to adhere to and colonize the perineum and urethra and migrate to the urinary tract where they establish an inflammatory response in the urothelium

18. Early Events in UPEC Pathogenesis • Bacterial adherence to vaginal and urothelial epithelial cells is an essential step in the initiation of UTIs • Adhesive characteristics of the bacteria, the receptive characteristics of the epithelial surface, and the fluid bathing both surfaces • UPEC expresses a number of adhesins that allow it to attach to urinary tract tissues • fimbrial or afimbrial, depending on whether the adhesin is displayed as part of a rigid fimbria or pilus

19. Bacteria may produce a number of antigenically and functionally different pili on the same cell; others produce a single type; in some, no pili are seen • Type 1 pili consist of a helical rod composed of repeating FimA subunits joined to a 3-nm wide distal tip structure containing the adhesin FimH • The most well-described pili are types 1, P and S

20. Type 1 pili are commonly expressed on both nonpathogenic and pathogenic E. coli and appear to facilitate bacterial colonization of the vaginal mucosa and bladder • The role of type 1 pili as a virulence factor in UTIs has been established • Interactions between FimH and receptors expressed on the luminal surface of the bladder epithelium are critical for the ability of many UPEC strains to colonize the bladder and cause disease

21. P (Mannose Resistant) Pili • P pili confer tropism to the kidney, the designation “P” standing for pyelonephritis • Between 70% and 80% of the pyelonephritic strains, but only 10% of the bowel isolates, had adhesive capacity • P pili were present in 91% of urinary strains causing pyelonephritis • 19% of strains causing cystitis, and 14% of strains causing asymptomatic bacteriuria

22. Epithelial Cell Receptivity • Adherence of E. coli to vaginal epithelial cells and uroepithelial cells • Receptor sites for UPEC on epithelial cells from women with recurrent UTIs is not limited to the vagina and thus suggest that a genotypic trait for epithelial cell receptivity may be a major susceptibility factor in UTIs

23. Variation in Receptivity • Hormones as estrogens in the pathogenesis of UTI is therefore a matter of great interest • increased epithelial receptivity for E. coli on the introital, urethral, and buccal mucosa that is characteristic of women susceptible to recurrent UTIs and may be a genotypic trait

24. Bladder Cells • fimH mediated binding to the bladder epithelium is the initial step in the intricate cascade of events leading to UTIs

25. Natural Defenses of the Urinary Tract • vaginal introitus, the periurethral area, and the urethra usually contain microorganisms such as lactobacilli, coagulase-negative staphylococci, corynebacteria, and streptococci that form a barrier against uropathogenic colonization • fastidious organisms that normally colonize the urethra will not multiply in urine and rarely cause UTIs • Urine from normal individuals may be inhibitory

26. Most inhibitory factors are the osmolality, urea concentration, organic acid concentration, and pH. Bacterial growth is inhibited by either very dilute urine or a high osmolality when associated with a low pH • The presence of glucose in the urine may facilitate infections • Uromodulin (Tamm-Horsfall protein), a kidney-derived mannosylated protein that is present in an extraordinarily high concentration in the urine (greater than 100 mg/mL), may play a defensive role by saturating all the mannose-binding sites of the type 1 pili

27. Alterations in Host Defense Mechanisms • Obstruction to urine flow at all anatomic levels is a key factor in increasing host susceptibility to UTI • Resulting stasis compromises bladder and renal defense mechanisms • Mild episodes of cystitis or pyelonephritis can become life-threatening when obstruction to urine flow becomes present

28. Vesicoureteral Reflux • Diabetes Mellitus • Human Immunodeficiency Virus • Spinal Cord Injury with High-Pressure Bladders • Pregnancy

29. CLINICAL MANIFESTATIONS • Cystitis is usually associated with dysuria, frequency, urgency, suprapubic pain, and hematuria • Pyelonephritis is classically associated with fever, chills, and flank pain • Nausea and vomiting may be present

30. Diagnosis • Diagnosis of UTI is made by direct or indirect analysis of the urine and is confirmed by urine culture • False-negative urinalysis and culture can occur in the presence of UTI • early in an infection when the numbers of bacteria and WBCs are low or diluted by increased fluid intake and subsequent diuresis • False-positive urinalysis and culture are caused by contamination of the urine specimen with bacteria and WBCs during collection

31. Urine Collection • Diagnostic accuracy can be improved by reducing bacterial contamination when the urine is collected

32. Urinalysis • Urinalysis provides rapid identification of bacteria and WBCs and presumptive diagnosis of UTI • Microscopic bacteriuria is found in more than 90% of infections with counts of 105 colony-forming units (cfu) per milliliter of urine or greater and is a highly specific finding • This important error (i.e., a false-negative result) occurs because of the limitation imposed by the microscope on the volume of urine that can be observed.

33. Pyuria • Tuberculosis is the well-recognized example of abacterial pyuria, staghorn calculi and stones of smaller size can produce intense pyuria with clumps of WBCs in the absence of UTI

34. Urine Culture • Urine must be refrigerated immediately on collection and should be cultured within 24 hours of refrigeration • Tissue and Stone Cultures

35. IMAGING TECHNIQUES • Imaging studies are not required in most cases of UTI • Infection in most men or a compromised host, febrile infections, signs or symptoms of urinary tract obstruction, failure to respond to appropriate therapy, and a pattern of recurrent infections suggesting bacterial persistence within the urinary tract warrant imaging for identification of underlying abnormalities

36. Indications for Radiological Investigation • Potential ureteral obstruction (e.g., due to stone, ureteral stricture, tumor)    • History of calculi, especially infection (struvite) stones    • Papillary necrosis (e.g., patients with sickle cell anemia, severe diabetes mellitus, analgesic abuse)   • History of genitourinary surgery that predisposes to obstruction, such as ureteral reimplantation or ureteral diversion   • Poor response to appropriate antimicrobial agents after 5 to 6 days of treatment    • Diabetes mellitus    • Polycystic kidneys in patients in dialysis or with severe renal insufficiency    • Neuropathic bladder    • Unusual infecting organisms, such as tuberculosis, fungus, or urea-splitting organisms (e.g., Proteus)

37. A UTI associated with possible urinary tract obstruction must be evaluated. • calculi, especially infection (struvite) stones; ureteral tumors; ureteral strictures; congenital obstructions; or previous genitourinary surgery, such as ureteral reimplantation or urinary diversion procedures, that may have caused obstruction. • Urologic imaging is indicated in patients whose symptoms of acute clinical pyelonephritis persist after 5 to 6 days of appropriate antimicrobial therapy; they often have perinephric or renal abscesses

38. Correctable Urologic Abnormalities That Cause Bacterial Persistence • Infection stones    • Chronic bacterial prostatitis    • Unilateral infected atrophic kidneys   • Ureteral duplication and ectopic ureters    • Foreign bodies/ Urethral diverticula and infected periurethral glands    • Unilateral medullary sponge kidneys    • Nonrefluxing, normal-appearing, infected ureteral stumps after nephrectomy    • Infected urachal cysts/Infected communicating cysts of the renal calyces /Papillary necrosis   • Perivesical abscess with fistula to bladder

39. Radiology • Plain Film of the Abdomen • Plain Film Renal Tomograms • Voiding Cystourethrogram • Ultrasonography • Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)

40. ANTIMICROBIAL THERAPY • Effective antimicrobial therapy must eliminate bacterial growth in the urinary tract. • (gm neg/pos/and anaerobes)      • Antimicrobial resistance is increasing because of excessive utilization    • Antimicrobial selection should be influenced by efficacy, safety, cost, and compliance

41. KIDNEY INFECTIONS • Renal infection is less prevalent than bladder infection • Classic symptoms of acute onset of fever, chills, and flank pain are usually indicative of renal infection • Unfortunately, the relationship between laboratory findings and the presence of renal infection often is poor • patients with significant renal infection may have sterile urine

42. Renal Infection (Bacterial Nephritis • Acute Focal or Multifocal Bacterial Nephritis • Emphysematous Pyelonephritis • Renal Abscess • Infected Hydronephrosis and Pyonephrosis • Chronic Pyelonephritis • Bacterial “Relapse” from a Normal Kidney • Xanthogranulomatous Pyelonephritis • Malacoplakia • Renal Echinococcosis