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Urinary Tract Infections

Charles S. Bryan, M.D. November 28, 2007

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) 

Overview of UTI by age and sex

Urinary tract infection  Significant bacteriuria  Asymptomatic bacteriuria  Acute pyelonephritis  Chronic pyelonephritis  ³Upper´ versus ³lower´ UTI  Urethral syndrome 






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) .

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

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  .Terms (4) Chronic bacterial pyelonephritis: Long-standing infection associated with active bacterial growth in the kidney.

Terms (5) ³Upper UTI´: infection above the level of the bladder  ³Lower UTI´: infection at or below the level of the bladder  ³Urethral syndrome´: clinical manifestations of lower UTI (dysuria. urgency) without significant bacteriuria  . frequency.

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

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  .Asymptomatic bacteriuria In patients with asymptomatic bacteriuria without infection.

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% .

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

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). .

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

.Urinary tract bacteriology (2)  In pyelonephritis. between 102 and 104 cfu/ml should may be significant. fewer colonies can be significant. the ³>105 cfu/ml´ rule breaks down. In catheterized patients in whom specimens are obtained directly from the catheter. Up to 20% of young women with acute uncomplicated pyelonephritis have between 103 and 104 cfu/ml.

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)  .

Urinary tract bacteriology (4) 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  Gram¶s .

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

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

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

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 .

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

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).  . coli to adhere to uroepithelial cells is associated with the presence of pili or fimbriae.  The ability of E.

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



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

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

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

aureus and Candida albicans.´  .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. but in general the kidney resists ³metastatic infection.

9% of a bladder inoculum of bacteria is promptly excreted by voiding. and biochemical differences in receptors on uroepithelial cells. 99.Mechanisms of lower UTI  Experimentally. .  Possible biologic explanations for the frequency of UTI in some women include: deficient antibodies in vaginal secretions.

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

.´ Its low pH (< 5.Mechanisms of upper UTI (2)  The renal medulla is an ³immunologic desert. 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.

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

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

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

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

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

geneticallydetermined carbohydrate receptors on uroepithelial cells .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. coli with unique markers. strains of E.



White blood cell casts  Highly significant!  Presence suggests pyelonephritis .



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


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


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


enterococci. and Proteus) notoriously tend to persist  .LongLong-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. Pseudomonas.

dribbling. urinary hesitancy. and burning  A risk of catheterization  .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 ³heaviness.´ rectal or perineal pain.

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