Urinary Tract Infections

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Urinary Tract Infections
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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)

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Overview of UTI by age and sex
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Terms

• Urinary tract infection
• Significant bacteriuria
• Asymptomatic bacteriuria
• Acute pyelonephritis
• Chronic pyelonephritis
• Upper versus lower UTI
• Urethral syndrome

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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 gt 105
  cfu/ml of urine (but lower counts can be
  significant)

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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

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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

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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

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Terms (6)

• Pyuria the presence of pus (WBCs 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

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Asymptomatic bacteriuria

• In patients with asymptomatic bacteriuria without
  infection, a colony count of gt 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

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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

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Frequency of significant bacteriuria (2)

• Congenital urologic disease 57
• Hydronephrosis nephrolithiasis 85
• Indwelling catheter, open drainage gt 48 hours
  98
  
  
  
  
  
  
  
  
  
  (reference Jackson et al, Arch Intern Med 1962
  110 663)
  
  

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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).

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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)

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Urinary tract bacteriology (2)

• In pyelonephritis, the gt105 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.

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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 gt 105/ml (thus, high
  positive predictive value)

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Urinary tract bacteriology (4)

• Grams stain of spun urine absence of visible
  bacteria makes gt 105 cfu/ml highly unlikely (that
  is, high negative predictive value)
• 20 of patients with urinary tract infection do
  not have pyuria

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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

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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

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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

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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

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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

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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.

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The role of bacterial virulence (2)

• Specificity has been associated with the
  Gal-alpha--gt4-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)

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Host defenses antibacterial properties of urine

• Osmolality (extremes of high or low osmolalities
  inhibit bacterial growth)
• High urea concentration
• High organic acid concentration
• pH

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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

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Host defensesmiscellaneous

• Mucopolysaccharide lining of the bladder
• Urinary immunoglobulins
• Spontaneous exfoliation of uroepithelial cells
  with bacterial detachment
• Mechanical flushing of micturition

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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.

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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.

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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.

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Mechanisms of upper UTI (2)

• The renal medulla is an immunologic desert. Its
  low pH (lt 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.

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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
  Fairleys bladder washout test antibody-coated
  bacteria test

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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.

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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

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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

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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.

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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

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White blood cell casts

• Highly significant!
• Presence suggests pyelonephritis

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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

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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)

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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

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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

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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