UTI

Urinary tract infection (UTI)

common, painful human illness
responsive to modern antibiotic therapy
asymptomatic (subclinical infection) or
symptomatic (disease)
the term UTI encompasses a variety of
clinical entities:
Asymptomatic bacteriuria (ABU)
Cystitis
Prostatitis
Pyelonephritis

Could be...

Uncomplicated UTI
acute cystitis or pyelonephritis in
nonpregnant outpatient women w/o
anatomic abnormalities or
instrumentation of the urinary tract
Complicated UTI

 Common in females (between 1 year and ~50 y.o)

In neonates, UTI is slightly higher among males
more commonly to have congenital urinary tract
anomalies
After 50 y.o, obstruction from prostatic hypertrophy
becomes common in men.
ABU is ~5% among women b/n ages 20 & 40 & as
high as 4050% among elderly women and men
5080% of women acquire at least 1 UTI during their
lifetimeuncomplicated cystitis mostly

 Independent Risk factors for acute cystitis:

Recent use of a diaphragm w/ spermicide,
frequent sexual intercourse, & history of UTI
Cystitis is temporally related to recent sexual
intercourse (60-fold increase in relative odds in
the 48 h after intercourse)
Risk factors for UTI in healthy postmenopausal
women:
sexual activity, diabetes mellitus, &
incontinence

 Factors independently associated with

pyelonephritis in young healthy women:
frequent sexual intercourse, new sexual
partner, UTI in the previous 12 months,
maternal history of UTI, diabetes, &
incontinence
2030% of women who have had 1 episode of
UTI will have recurrent episodes.
Early recurrence (within 2 weeks): relapse
rather than reinfection
likelihood of recurrence decreases w/
increasing time since the last infection

 Many factors predisposing women to

cystitis also increase the risk of
pyelonephritis. The common risk factors
for cystitis and pyelonephritis are not
surprising given that pyelonephritis
typically arises through the ascent of
bacteria from the bladder to the upper
urinary tract. However, pyelonephritis
can occur without clear antecedent
cystitis
A Cochrane meta-analysis found that
treatment of ABU in pregnant women

 The only consistently documented behavioral

risk factors for recurrent UTI frequent
sexual intercourse & spermicide use
In postmenopausal women, anatomic factors
affecting bladder emptying, such as
cystoceles, urinary incontinence, and residual
urine most strongly associated w/ recurrent
UTI
ABU during pregnancy is associated w/
preterm birth & perinatal mortality for the
fetus & w/ pyelonephritis for the mother.
Lack of circumcision increased risk of UTI
(E. coli is more likely to colonize the glans and

 Womenbut not menwith diabetes have 2 to

3-fold higher rate of ABU and UTI.
Increased duration of diabetes & use of insulin
higher risk of UTI among women w/ diabetes
Poor bladder function, obstruction in urinary
flow, & incomplete voiding additional factors
common in patients w/ diabetes that increase
the risk of UTI
Impaired cytokine secretion may contribute to
ABU in diabetic women.

Etiology
uropathogens vary by clinical syndrome &
geography
usually enteric gram-negative rods
acute uncomplicated cystitis in the US, Europe
& Brazil
E. coli: 7590%
Staphylococcus saprophyticus: 515%
( younger women)
Klebsiella sp, Proteus sp, Enterococcus sp,
Citrobacter sp, & other organisms: 510%
The spectrum of agents causing uncomplicated
pyelonephritis is similar; E. coli predominating.

 complicated UTI:
E. coli remains the predominant organism
Other aerobic gram-negative rods (Klebsiella
sp, Proteus sp, Citrobacter sp, Acinetobacter
sp, Morganella sp, Pseudomonas aeruginosa)
also are frequently isolated
Gram-positive bacteria (enterococci &
Staphylococcus aureus), & yeasts: also
important pathogens in complicated UTI

Pathogenesis
majority of UTIs: bacteria establish
infection by ascending from the
urethra to the bladder
introduction of bacteria into the
bladder does not inevitably lead to
sustained and symptomatic infection
interplay of host, pathogen, &
environmental factors determines
whether tissue invasion &

 Bacteria can also gain access to the urinary

tract through the bloodstream (<2%)
results from bacteremia caused by virulent
organisms (Salmonella and S. aureus)
Vaginal ecology is an important
environmental factor affecting the risk of
UTI.
Colonization of the vaginal introitus &
perirurethral area w/ organisms from the
intestinal flora (usually E. coli) is the critical
initial step in the pathogenesis of UTI.
Any condition that permits urinary stasis or

 Inhibition of ureteral peristalsis and

decreased ureteral tone leading to
vesicoureteral reflux important in the
pathogenesis of pyelonephritis in
pregnant women
Anatomic factorsspecifically, the
distance of the urethra from the anus :
considered to be the primary reason
why UTI is predominantly an illness of
young women

Host factors
Genetic background of the host influences the
individual's susceptibility to recurrent UTI
(among women)
A familial predisposition to UTI &
pyelonephritis is well documented.
Women with recurrent UTI: more likely to have
had their 1st UTI before 15 y.o. & have a
maternal history of UTI
Pathogenesis of familial predisposition to
recurrent UTI persistent vaginal colonization

 Vaginal and periurethral mucosal cells

from women with recurrent UTI bind
threefold more uropathogenic bacteria
than do mucosal cells from women
without recurrent infection. Epithelial
cells from susceptible women may
possess specific types or greater
numbers of receptors to which E. coli
can bind, thereby facilitating
colonization and invasion

 Mutations in host response genes (those

coding for Toll-like receptors & IL 8 receptor)
also linked to recurrent UTI &
pyelonephritis
Polymorphisms in the IL 8specific receptor
gene CXCR1 increased susceptibility to
pyelonephritis
Lower-level expression of CXCR1 on the
surface of neutrophils impairs neutrophildependent host defense against bacterial
invasion of the renal parenchyma.

Virulence Factors
P fimbriae
best studied adhesin
hairlike protein structures that interact w/
specific receptor on renal epithelial cells
(blood group antigen P)
important in the pathogenesis of
pyelonephritis & bloodstream invasion from
the kidney
Type 1 pilus (fimbria)
E. coli strains possess but not all E. coli
strains express

Clinical manifestations

Asymptomatic Bacteriuria
considered ONLY when patient does not have local or
systemic symptoms referable to the urinary tract
Cystitis
typical symptoms: dysuria, urinary frequency & urgency
nocturia, hesitancy, suprapubic discomfort, gross
hematuria are often noted
Unilateral back/flank pain indication that upper urinary
tract is involved
Fever indication of invasive infection of the kidney or
prostate

 Pyelonephritis
Mild pyelonephritis: low-grade fever with/without
low-back or costovertebral-angle pain
Severe pyelonephritis: high fever, rigors, nausea,
vomiting, & flank &/or loin pain
symptoms are generally acute in onset
symptoms of cystitis may not be present
Fever is the main feature distinguishing cystitis &
pyelonephritis.
Fever high, spiking "picket-fence" pattern,
resolves over 72 h of tx
Bacteremia develops in 2030% of cases

 Emphysematous pyelonephritis
severe form
production of gas in renal & perinephric tissues
occurs almost exclusively in diabetic patients
Xanthogranulomatous pyelonephritis
occurs when chronic urinary obstruction (often by
staghorn calculi), together with chronic infection,
leads to suppurative destruction of renal tissue
intraparenchymal abscess formation
suspected when a patient has continued fever &/or
bacteremia despite antibacterial therapy

 Prostatitis
infectious & noninfectious abnormalities of
prostate gland
Infections: acute or chronic, almost always
bacterial in nature
far less common than noninfectious
entity of chronic pelvic pain
syndrome (formerly chronic prostatitis)
Acute bacterial prostatitis
Sxs: dysuria, frequency, & pain in the
prostatic, pelvic, or perineal area.
(+) fever & chills, symptoms of bladder
outlet obstruction are common

 Chronic bacterial prostatitis

recurrent episodes of cystitis, sometimes
w/ pelvic & perineal pain
Men who present with recurrent cystitis
should be evaluated for a prostatic focus.
Complicated UTI
symptomatic episode of cystitis or
pyelonephritis in a man or woman w/
anatomic predisposition to infection, w/
foreign body in the urinary tract, or w/
factors predisposing to a delayed response
to therapy

Diagnostic flowchart

Differential Diagnoses:
dysuria
cervicitis (C. trachomatis, Neisseria
gonorrhoeae)
vaginitis (Candida albicans, Trichomonas
vaginalis)
herpetic urethritis, interstitial cystitis, &
noninfectious vaginal or vulvar irritation
Women with >1 sexual partner & inconsistent
use of condoms high risk for both UTI STD

Diagnostics

Useful diagnostic tools:

urine dipstick test & urinalysis (provide point-of-care
information)
urine culture (confirm a prior diagnosis)
urine dipstick test can confirm the diagnosis of
uncomplicated cystitis in a patient with high pretest
probability disease.
A dipstick test (-) for nitrite & leukocyte esterase in the
same type of patient should prompt consideration of other
explanations for the symptoms & collection of urine C/S
A (-) dipstick test is not sufficiently sensitive to rule out
bacteriuria in pregnant women
dipstick test highly specific in men in men and highly
sensitive in noncatheterized nursing home residents

 Urine microscopy reveals

pyuria (nearly all cases)
hematuria (30%)
Urine culture
"gold standard" for UTI
women w/ Sxs of cystitis: colony count
threshold of >102 bacteria/mL is more
sensitive (95%) & specific (85%) than
105/mL for the diagnosis of acute cystitis
In men: 103/mL is the minimal level
indicating infection
If mixed bacterial species sample is
contaminated

 Uncomplicated cystitis in women

can be treated on the basis of history alone
if the symptoms are not specific or history
is not reliable urine dipstick test should
be performed
(+) nitrite or leukocyte esterase in a
woman w/ 1 symptom of UTI increases the
probability of UTI from 50% to ~80%
empirical treatment can be considered w/o
further testing

 Cystitis in Men
Ssx are similar to women
urine culture is strongly recommended
documentation of bacteriuria can
differentiate the less common syndromes
of acute and chronic bacterial prostatitis
from the very common entity of chronic
pelvic pain syndrome
If the diagnosis is unclear, localization cultures
by 2 or 4-glass Meares-Stamey test (urine
collection after prostate massage) should be
done to differentiate b/n bacterial &
nonbacterial prostatic syndromes refer to a

 Men with febrile UTI often have an elevated

PSA & an enlarged prostate & seminal
vesicles on UTZ indicating prostate
involvement
In 85 men with febrile UTI, symptoms of
urinary retention, early recurrence of UTI,
hematuria at follow-up, & voiding difficulties
were predictive of surgically correctable
disorders.
Men with none of these symptoms had
normal upper and lower urinary tracts on
urologic workup.

diagnosis of ABU involves both

microbiologic and clinical criteria.
105 bacterial cfu/mL + no signs
or symptoms referable to UTI

How to treat UTI?

 Fluoroquinolones: first-line therapy for acute

uncomplicated pyelonephritis
oral ciprofloxacin (500 mg BID daily,
with/without an initial IV 400-mg dose):
highly effective for initial management of
pyelonephritis in the OPD
Oral TMP-SMX (1 double-strength tablet BID
daily x 14 days): also effective for acute
uncomplicated pyelonephritis if uropathogen
is susceptible
If the pathogen's susceptibility is unknown &
TMP-SMX is used initial IV 1-g dose of
ceftriaxone is recommended

 Options for IV therapy for uncomplicated

pyelonephritis:
fluoroquinolones
aminoglycoside with or without ampicillin
extended-spectrum cephalosporin +/aminoglycoside
carbapenem
Combinations of a -lactam & a -lactamase
inhibitor (e.g., ampicillin-sulbactam, ticarcillinclavulanate, and piperacillin-tazobactam) or
imipenem-cilastatin
patients with more complicated histories,
previous episodes of pyelonephritis, or recent
urinary tract manipulations (guided by urine

UTI in Pregnant Women

Nitrofurantoin, ampicillin, & cephalosporins are
considered relatively safe in early pregnancy
Ampicillin & cephalosporins
used extensively in pregnancy
drugs of choice for treatment of
asymptomatic or symptomatic UTI in this
group
pregnant women with overt pyelonephritis
parenteral -lactam therapy +/aminoglycosides is the standard of care

UTI in Men
GOAL: eradicate prostatic infection & bladder
infection
uncomplicated UTI: 7-14-day FQs or TMP-SMX

If acute bacterial prostatitis is suspected,

treatment should be initiated after urine &
blood are obtained for cultures.
Tx: 24 weeks
Chronic bacterial prostatitis: 4- to 6-week
course

CAUTI
bacteriuria & symptoms in a catheterized patient
accepted threshold for bacteriuria: 103 cfu/mL to 105
cfu/mL
formation of biofilm (a living layer of uropathogens)
on the urinary catheter is central to the pathogenesis
oOrganisms in a biofilm are relatively resistant to
killing by antibiotics
The best strategy for prevention of CAUTI: avoid
insertion of unnecessary catheters & to remove
catheters once they are no longer necessary
Tx: 7- to 14 days of antibiotics is recommended

Candiduria
Common for patients in the ICU, those taking
broad-spectrum antimicrobial drugs, & those w/ DM
C. albicans: most common isolate
Treatment is recommended for symptomatic
cystitis or APN & for those high risk for
disseminated disease ( neutropenic, those who are
undergoing urologic manipulation, & low-birthweight infants)
Fluconazole (200400 mg/d for 14 days): first-line
TX
oral flucytosine &/or parenteral amphotericin B: for
resistant to fluconazole

Prevention of Recurrent UTI

3 prophylactic strategies are available:
continuous, postcoital, or patient-initiated therapy
Continuous & postcoital prophylaxis
low doses of TMP-SMX, FQ, or nitrofurantoin
all highly effective during the period of active
antibiotic intake
prophylactic regimen is prescribed for 6 months
& then discontinued
If bothersome infections recur, the prophylactic
program can be reinstituted for a longer period.

 Patient-initiated therapy: supplying

patient w/ materials for urine culture &
self-medication with a course of
antibiotics at the first symptoms of
infection.