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
 Terms
■ Urinary tract infection
■ Significant bacteriuria
■ Asymptomatic bacteriuria
■ Acute pyelonephritis
■ Chronic pyelonephritis
■ “Upper” versus “lower” 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)
 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
 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
 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
 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
 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
Frequency of significant bacteriuria
■ Afterone bladder catheterization: 2%
■ Medical outpatients: 5%
■ Pregnancy at term: 10%
■ Hypertensive patients: 14%
■ Diabetes mellitus: 20%
■ Women with cystocoele: 23%
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)

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).
 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)
 Urinary tract bacteriology (2)
■ Inpyelonephritis, 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.
 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)
■ 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
 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
 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
 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
 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
 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
 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.
 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)
 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:
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
 Host defenses:
miscellaneous
■ Mucopolysaccharide lining of the
bladder
■ Urinary immunoglobulins
■ Spontaneous exfoliation of
uroepithelial cells with bacterial
detachment
■ Mechanical flushing of micturition
 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.”
 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.
 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.
 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.
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
 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.
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
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
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.
 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
 White blood cell casts
 Highly
significant!
 Presence
suggests
pyelonephritis
 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
 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)
 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
 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
 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