1. Urinary Tract Infections

2. Overview of UTI 7 million office visits yearly
1 million hospitalizations
About 2/3rds of patients are women; 40% to 50% of women have UTI at some point during their lives
Important complications of pregnancy, diabetes mellitus, polycystic disease, renal transplantation, conditions that impede urine flow (structural and neurologic)

3. Overview of UTI by age and sex

4. Terms Urinary tract infection Significant bacteriuria
Asymptomatic bacteriuria
Acute pyelonephritis
Chronic pyelonephritis
“Upper” versus “lower” UTI
Urethral syndrome

11. Terms (2)
UTI: the finding of microorganisms in bladder urine with or without clinical symptoms and with or without renal disease
Significant bacteriuria: the finding of > 105 cfu/ml of urine (but lower counts can be significant)

12. Terms (3)
Asymptomatic bacteriuria: Significant bacteriuria without clinical symptoms or other abnormal findings.
Acute bacterial pyelonephritis: a clinical syndrome of fever, flank pain, and tenderness, often with constitutional symptoms, leukocyte casts in the urine, and bacteriuria; or histologic findings thereof

13. Terms (4)
Chronic bacterial pyelonephritis: Long-standing infection associated with active bacterial growth in the kidney; or the residuum of lesions caused by such infection in the past
Chronic interstitial nephritis: renal disease with histologic findings resembling chronic bacterial pyelonephritis but without evidence of infection

14. Terms (5) “Upper UTI”: infection above the level of the bladder
“Lower UTI”: infection at or below the level of the bladder
“Urethral syndrome”: clinical manifestations of lower UTI (dysuria, frequency, urgency) without significant bacteriuria

15. Terms (6)
Pyuria: the presence of pus (WBC’s [leukocytes] in urine, which may or may not be caused by UTI. The preferred method for quantitation is enumeration in unspun urine using a counting chamber. The leukocyte esterase nitrite test has a sensitivity of between 70% and 90% for symptomatic UTI

16. Asymptomatic bacteriuria
In patients with asymptomatic bacteriuria without infection, a colony count of > 105 cfu/ml defines infection
Screening has little apparent value in adults except during pregnancy and prior to urologic surgery
Up to 40% of elderly men and women have asymptomatic bacteriuria

17. Frequency of significant bacteriuria
After one bladder catheterization: 2%
Medical outpatients: 5%
Pregnancy at term: 10%
Hypertensive patients: 14%
Diabetes mellitus: 20%
Women with cystocoele: 23%

18. Frequency of significant bacteriuria (2)
Congenital urologic disease: 57%
Hydronephrosis; nephrolithiasis: 85%
Indwelling catheter, open drainage > 48 hours: 98% (reference: Jackson et al, Arch Intern Med 1962; 110: 663)

19. Screening for significant bacteriuria
Screening for asymptomatic bacteriuria in adults has little value except for two situations: pregnancy (because of the high risk of acute pyelonephritis with its accompanying risk of fetal complications) and prior to urologic surgery (because of the risk of postoperative sepsis).

20. Urinary tract bacteriology
At room temperature, the doubling time of common aerobic bacteria is about 20 minutes
Some contaminants in voided urine: Lactobacilli, Cornyebacterium species, Gardnerella, alpha-hemolytic streptococci, anaerobes
Any bacterial growth is significant if the specimen is collected from a normally-sterile site (e.g., direct bladder puncture)

21. Urinary tract bacteriology (2)
In pyelonephritis, the “>105 cfu/ml” rule breaks down; fewer colonies can be significant. Up to 20% of young women with acute uncomplicated pyelonephritis have between 103 and 104 cfu/ml. In catheterized patients in whom specimens are obtained directly from the catheter, between 102 and 104 cfu/ml should may be significant.

22. Urinary tract bacteriology (3)
Patients with uncomplicated infection almost invariably have a single organism; this is not necessarily the case with complicated infections
Unspun midstream urine: One bacterium/high-powered field (hpf) correlates with > 105/ml (thus, high positive predictive value)

23. Urinary tract bacteriology (4)
Gram’s stain of spun urine: absence of visible bacteria makes > 105 cfu/ml highly unlikely (that is, high negative predictive value)
20% of patients with urinary tract infection do not have pyuria

24. Etiology of community-acquired UTI
Aerobic gram-negative rods most often
E. coli accounts for about 90%
Staphylococcus saprophyticus has been increasingly appreciated in recent years (with seasonality, tending to occur in the summer)
Rare: anaerobes; pyogenic cocci; viruses

25. Etiology of nosocomial UTI
E. coli is the most common pathogen
However, also common are other Enterobacteriacae (Proteus, Klebsiella, Enterobacter, Serratia, Providencia species) and Pseudomonadaceae (notably, Pseudomonas aeruginosa)
Enterococci: often in obstructive uropathy
Yeasts: Candida albicans, others

26. Urease-producing microorganisms
Urease splits urea into ammonia, which has a direct toxic effect on the kidney; inactivates C4, and alkalinizes the urine with production of struvite crystals (MgNH4P04.6H20) crystals
Proteus mirabilis most often; also Providencia, Morganella, S. saprophyticus, Klebsiella, Corynebacterium D2; mycoplasma
Eradicate if at all possible

27. UTI in children
Newborns: overall rate is about 1% (higher in males than in females)
Preschool children: UTI is 10 to 20 times more common in girls
School-aged children: about 1.2% of schoolgirls have bacteriuria on any given day

28. UTI in adults
Women: bacteriuria increases with age and sexual activity
Men: bacteriuria is rare before age 50 (and as a corollary, calls for more aggressive evaluation than in women). Subsequently, bacteriuria increases with onset of prostatism

29. Role of bacterial virulence in UTI
Bacterial adherence to uroepithelial cells involves specific binding of bacterial surface receptors (adhesins) to complementary components on the epithelial cells (receptors).
The ability of E. coli to adhere to uroepithelial cells is associated with the presence of pili or fimbriae.

30. The role of bacterial virulence (2)
Specificity has been associated with the Gal-alpha-->4-Gal specific adhesion localized at the fimbrial polymer.
However, virulence of E. coli strains does not seem to depend upon a single virulence factor. There may well be an additive effect among multiple virulence factors (including adhesins, hemolysin, capsular polysaccharide, aerobactin)

33. Host defenses: antibacterial properties of urine
Osmolality (extremes of high or low osmolalities inhibit bacterial growth)
High urea concentration
High organic acid concentration pH

34. Host defenses: anti-adherence mechanisms
Bacterial interference (naturally endogenous bacteria in the urethra, vagina, and periurethral region)
Urinary oligosaccharides (have the potential to detach epithelial-bound E. coli
Tamm-Horsfall protein (uromucoid): coating of E. coli by this protein might prevent attachment

35. Host defenses: miscellaneous
Mucopolysaccharide lining of the bladder
Urinary immunoglobulins
Spontaneous exfoliation of uroepithelial cells with bacterial detachment
Mechanical flushing of micturition

36. Routes of urinary tract infection
Ascending infection is thought to be the common route of nearly all forms of urinary tract infection (bacteria initially colonize periurethral tissues)
Descending (hematogenous) infection can be important for a few organisms such as S. aureus and Candida albicans, but in general the kidney resists “metastatic infection.”

37. Mechanisms of lower UTI
Experimentally, 99.9% of a bladder inoculum of bacteria is promptly excreted by voiding.
Possible biologic explanations for the frequency of UTI in some women include: deficient antibodies in vaginal secretions; and biochemical differences in receptors on uroepithelial cells.

38. Mechanisms of upper UTI
Ascent of bacteria from the bladder to the kidneys is promoted by obstruction and by reflux. In addition, motile bacteria can ascend against the flow of a column of urine. Gram-negative bacteria (or endotoxin derived from them) can inhibit ureteral peristalsis.

39. Mechanisms of upper UTI (2)
The renal medulla is an “immunologic desert.” Its low pH (< 5. 5) and high osmolality (which may reach 1300 mOsm/LK with a sodium of 425 mM and urea of 850 mM) drastically interfere not only with all aspects of leukocyte function but also with antibody and complement function.

40. Localization of upper versus lower UTI
Indirect: pattern of recurrence (i.e., same organism?); maximum urinary concentration; water loading test; serum antibodies; cellular excretion; urinary proteins
Direct: renal biopsy; ureteral catheterization; Fairley’s bladder washout test; antibody-coated bacteria test

41. Localization of upper versus lower UTI (2): in practice
Frequency, dysuria, and urgency (lower UTI symptoms) can occur with upper UTI as well.
Fever and flank pain indicate acute upper urinary tract infection.
Scarring of the kidney by imaging procedures suggests chronic UTI.
The distinction is sometimes difficult.

42. Acute uncomplicated cystitis in young women
Acute dysuria in young women usually indicates: acute bacterial cystitis; the urethral syndrome; or vaginitis
Acute bacterial cystitis is usually characterized by sudden onset, multiple urinary symptoms, pyuria, and sometimes hematuria

43. Acute uncomplicated cystitis in young women (2)
Although most patients have lower urinary symptoms only, 30% to 50% may have subclinical renal involvement
Causes: E. coli (80%), S. saprophyticus (10% to 15%), and occasionally Klebsiella, Proteus mirabilis, and other microorganisms

44. Acute uncomplicated cystitis in young women (3)
A short course of antibiotics (e.g., three days) usually suffices
Abbreviated work-ups (e.g., leukocyte-esterase nitrite test) without culture or routine follow-up is now acceptable for typical encounters.

45. Acute uncomplicated pyelonephritis in young women
Largely a clinical diagnosis
Pyuria is usually present; about 20% have positive blood cultures; causative organisms the same as with cystitis
Predisposing factors: structural abnormalities; strains of E. coli with unique markers; genetically-determined carbohydrate receptors on uroepithelial cells

48. White blood cell casts Highly significant!
Presence suggests pyelonephritis

51. Recurrent UTIs in women
Between 20% and 25% of young women with acute uncomplicated cystitis have 2 or more infections per year, usually due to reinfection with a different E. coli strain
Predisposing factors: genetically-determined receptors on uroepithelial cells; diaphragm-spermicide use

53. Complicated UTIs
Definition: UTI in patients with predisposing anatomic, functional, or metabolic abnormalities
Spectrum of organisms is skewed toward difficult-to-treat pathogens (e.g., Pseudomonas sp., yeasts, enterococci, Enterobacteriaceae other than E. coli)

55. Catheter-associated UTI
Over 1 million catheter-associated UTIs occur in the United States each year
Risk factors: female sex; duration of catheterization; disconnecting the junction between the catheter and the collecting tube

57. Long-term bladder catheterization
Incidence of significant bacteriuria in patients who are not receiving antibiotics is 8% to 10% per day
More than 85% of patients have at least two strains of bacteria and 10% have more than five strains
Some species (notably, enterococci, Pseudomonas, and Proteus) notoriously tend to persist

58. Prostatitis
Relapsing acute urinary tract infection in men caused by the same bacterial species often suggests chronic prostatitis with periodic spill-over into the bladder
Symptoms: pelvic “heaviness,” rectal or perineal pain, urinary hesitancy, dribbling, and burning
A risk of catheterization