URINARY TRACT INFECTION

Dr Gaurav Singh
DM Nephrology Resident
 DEFINITION AND CATEGORIES
• Presence of bacteria in the urinary tract, usually
accompanied by white blood cells and inflammatory
cytokines in the urine.

• It includes –
1. Asymptomatic Bacteriuria(ASB)
2. Symptomatic uncomplicated UTI which include cystitis,
prostatitis and pyelonephritis
3. Complicated UTI
4. CAUTI – Catheter associated UTI
 Complicated vs Uncomplicated
• Uncomplicated urinary tract infection - acute
cystitis or pyelonephritis in nonpregnant
outpatient women or men without anatomic
abnormalities or instrumentation of the
urinary tract
• Complicated urinary tract infection
encompasses all other types of UTI.
• Recurrent urinary tract infection(2 or more
episodes in an year) may not necessarily be
complicated.
 ETIOLOGY

• Enteric gram-negative rods that have migrated to

the urinary tract causes UTI.

• BACTERIOLOGY
1.E. coli accounts for 75–90%
[Link] saprophyticus for 5–15% (esp with
younger women)
[Link], Proteus, Enterococcus, and Citrobacter
species 5–10%
• In complicated UTI and CAUTI –

1. E. coli(predominant)

2. Aerobic gram-negative rods-Pseudomonas

aeruginosa and Klebsiella, Proteus, Citrobacter,
Acinetobacter, and Morganella species

3. Gram-positive bacteria (e.g., enterococci and

Staphylococcus aureus) and yeast.
 PATHOGENESIS
1. In the majority of UTIs, bacteria establish
infection by ascending from the urethra to the
bladder. Continuing ascent up the ureter to the
kidney is the pathway for most renal
parenchymal infections.

2. The interplay of host, pathogen, and

environmental factors determines whether
tissue invasion and symptomatic infection will
ensue
3. Any foreign body - catheter or stone, provides an inert
surface for bacterial colonization.

4. Hematogenous spread accounts for <2% of

documented UTIs and results from bacteremia caused
by virulent organisms - Salmonella and S. aureus.

5. The pathogenesis of candiduria is distinct in that the

hematogenous route is common. The presence of
Candida in the urine of a non-instrumented
immunocompetent patient implies either genital
contamination or potentially widespread visceral
dissemination.
TRIANGLE OF PATHOGENESIS
• Environmental Factors
A. VAGINAL ECOLOGY - Important environmental
factor in women.
1. Colonization of the vaginal introitus and
periurethral area from the intestinal flora – in
women with low hygiene.
2. Sexual intercourse
3. Nonoxynol-9 in spermicide use (toxic to vaginal
lactobacill)
4. In postmenopausal women, the vaginal
lactobacilli are replaced with gram-negative
bacteria.
• B. ANATOMIC AND FUNCTIONAL ABNORMALITIES –
1. Urinary stasis or obstruction predisposes the individual
to UTI.
2. Foreign bodies like stones or urinary catheters-
colonization(biofilm).
3. Vesicoureteral reflux, ureteral obstruction secondary to
prostatic hypertrophy, neurogenic bladder, and urinary
diversion surgery
[Link] of ureteral peristalsis and decreased ureteral
tone leading to vesicoureteral reflux – pathogenesis of
pyelonephritis in pregnant women.
[Link] of the urethra from the anus— the primary
reason why UTI is predominantly an illness of young women
• Host Factor - A familial disposition to UTI and to
pyelonephritis is well documented.

Vaginal and periurethral mucosal cells from women

with recurrent UTI bind threefold more bacteria
than from women without recurrent infection.

Mutations in host genes (Toll-like receptors and the

interleukin 8 receptor) also have been linked to
recurrent UTI and pyelonephritis.
• Microbial Factors - strains of E. coli that cause
invasive symptomatic infection in normal hosts
possess and express genetic virulence factors,
including surface adhesins that mediate binding . P
fimbriae, hair-like protein structure & are important
in the pathogenesis of pyelonephritis and
subsequent bloodstream invasion from the kidney.
• Another adhesin is the type 1 pilus (fimbria), which
all E. coli strains possess but not all E. coli strains
express. Type 1 pili initiate E. coli bladder infection;.
 APPROACH

• CYSTITIS –
1. dysuria, urinary frequency, and urgency.
2. Nocturia, hesitancy, suprapubic discomfort, and
gross hematuria may be found
3. Unilateral back or flank pain is generally an
indication that the upper urinary tract is involved.
4. No Fever as it is an indication of invasive
infection of either the kidney or the prostate.
 PYELONEPHRITIS
• Mild pyelonephritis - low-grade fever with or without lower-
back or costovertebral-angle pain,
• severe pyelonephritis - high fever, rigors, nausea, vomiting,
and flank and/or loin pain.
• Symptoms - acute in onset, and symptoms of cystitis may not
be present.
• Fever is the main feature distinguishing cystitis from
pyelonephritis.
• High spiking “picket-fence” pattern and resolves over 72 h of
therapy.
• Bacteremia develops in 20–30% of cases.
• In diabetes pt present with obstructive uropathy associated
with acute papillary necrosis when the sloughed papillae
obstruct the ureter. And APN complicated by obstruction,
sickle cell disease, analgesic nephropathy, or combinations of
these conditions. Serum creat rises in B/l APN.
• Emphysematous pyelonephritis - severe form associated with the
production of gas in renal and perinephric tissues and occurs
almost exclusively in diabetic patients.
Percutaneous drainage as initial therapy and can be followed by
elective nephrectomy as needed.

• Xanthogranulomatous pyelonephritis - chronic urinary obstruction

(often by staghorn calculi), together with chronic infection, leads to
suppurative destruction of renal tissue. It is treated with
nephrectomy.
On pathologic examination, the residual renal tissue frequently has
a yellow coloration, with infiltration by lipid-laden macrophages.

• Pyelonephritis can be complicated by intraparenchymal abscess

formation; this should be suspected when a patient has continued
fever and/or bacteremia despite antibacterial therapy.
 PROSTATITIS

• Prostatitis - infectious and noninfectious abnormalities of the

prostate gland.
• Infections can be acute or chronic, are almost always bacterial in
nature, and are far less common than the noninfectious entity
chronic pelvic pain syndrome (formerly known as chronic
prostatitis).
• Acute bacterial prostatitis - dysuria, frequency, and pain in the
prostatic pelvic or perineal area.
Fever and chills are usually present, and symptoms of bladder
outlet obstruction are common.
• Chronic bacterial prostatitis presents more insidiously as
recurrent episodes of cystitis, sometimes with associated pelvic
and perineal pain. Men who present with recurrent cystitis should
be evaluated for a prostatic focus as well as urinary retention.
• first-line agents include TMP-SMX and nitrofurantoin.
• Second-line agents include β-lactams.
• There is increasing use of fosfomycin for UTIs (including
complicated infections), particularly for infections caused by
multidrug-resistant E. coli.
• According to USFDA, fluoroquinolones should not be used
for uncomplicated cystitis unless no alternatives are
available.
• Drugs with minimal effect on fecal flora - pivmecillinam,
fosfomycin, and nitrofurantoin.
• trimethoprim, TMP-SMX, quinolones, and ampicillin affect
the fecal flora more significantly and are the agents for
which rising resistance levels have been documented.
• The fluoroquinolones commonly used for UTI include ciprofloxacin and
levofloxacin. The two main concerns about fluoroquinolone use for acute
cystitis are the
• the propagation of fluoroquinolone resistance, not only among
uropathogens but also among other organisms causing more serious and
difficult-to-treat infections at other sites
• Achilles tendon rupture. Other potential side effects include irreversible
neuropathy.
• Resistance to nitrofurantoin remains low despite >60 years of use, as
several mutational steps are required for the development of bacterial
resistance.
• Nitrofurantoin remains highly active against E. coli and most non–E. coli
isolates.
• Proteus, Pseudomonas, Serratia, Enterobacter, and yeasts are all
intrinsically resistant to this drug.
• Guidelines now recommend a 5-day course.
• Nitrofurantoin does not reach significant levels in tissue and cannot be
 PYELONEPHRITIS
• tissue-invasive disease,
• Goal os to eradicate the causative organism and should reach therapeutic
blood levels quickly.
• Fluoroquinolones the first-line therapy for acute uncomplicated
pyelonephritis.
• Oral TMP-SMX (one double-strength tablet twice daily for 14 days) also
is effective for treatment of acute uncomplicated pyelonephritis if the
uropathogen is known to be susceptible.
• If the pathogen’s susceptibility is unknown and TMP-SMX is used, an
initial IV 1-g dose of ceftriaxone is recommended. Oral β-lactam agents
are less effective. Options for parenteral therapy for uncomplicated
pyelonephritis include fluoroquinolones, an extended-spectrum
cephalosporin with or without an aminoglycoside, or a carbapenem.
• Combinations of a β-lactam and a β-lactamase inhibitor or a
carbapenem can be used in patients with more complicated histories,
previous episodes of pyelonephritis, anticipated antimicrobial resistance,
or recent urinary tract manipulations; in general, the treatment of such
patients should be guided by urine culture results.
 UTI IN PREGNANT WOMEN
• Nitrofurantoin, ampicillin, and the cephalosporins are
considered relatively safe in early pregnancy.
• Sulfonamides should be avoided both in the first trimester
( teratogenic effects) and near term (kernicterus).
• Fluoroquinolones are avoided - fetal cartilage development.

• Ampicillin and the cephalosporins are the drugs of choice for the
treatment of asymptomatic or symptomatic UTI in pregnancy.
• Generally, pregnant women with ASB are treated for 4–7 days in
the absence of evidence to support single-dose therapy.
• For pregnant women with overt pyelonephritis, parenteral β-
lactam therapy with or without aminoglycosides is the standard
of care.
 UTI IN MEN

• Prostate is involved in the most cases of febrile UTI in men, so goal

in these patients is to eradicate the prostatic infection as well as
the bladder infection.
• So 7- to 14-day course of a fluoroquinolone or TMP-SMX is
recommended if the uropathogen is susceptible.
• If acute bacterial prostatitis is suspected, antimicrobial therapy
should be initiated after urine and blood are obtained for cultures.
Therapy can be tailored to urine culture results and should be
continued for 2–4 weeks.
• For documented chronic bacterial prostatitis, a 4- to 6-week
course of antibiotics is often necessary. Recurrences, which are not
uncommon in chronic prostatitis, often warrant a 12-week course
of treatment.
COMPLICATED UTI
• Complicated UTI - structural and functional abnormalities.
• therapy for complicated UTI - individualized and guided by urine
culture results.

ASYMPTOMATIC BACTERIURIA
• Only in pregnant women, persons undergoing urologic surgery,
neutropenic patients and renal transplant recipients, ASB needs
treatment. It is directed by urine culture results.

• In all other populations, screening for and treatment of ASB are

discouraged. If catheter-associated bacteriuria are asymptomatic,
they don’t need antimicrobial therapy.
CATHETER-ASSOCIATED UTI
• The signs and symptoms similar to UTI including pain, urgency, dysuria, fever,
peripheral leukocytosis, and pyuria.
• The accepted threshold for bacteriuria to meet the definition of CAUTI is ≥103
CFU/mL of urine, while the threshold for bacteriuria to meet the definition of
ASB is ≥105 CFU/mL.
• Bacteriuria is inevitable with long-term catheter use.
• Urine culture results are essential to guide treatment. Catheter is changed
frequently in its treatment. The goal is to remove biofilm-associated
organisms acts as nidus.
Pathology studies reveal that many patients with long-term catheters have
occult pyelonephritis.
• In general, a 7- to 14-day course of antibiotics is recommended, but further
studies on the optimal duration of therapy are needed.
• Prevention of CAUTI is to avoid insertion of unnecessary catheters and to
remove catheters when no longer [Link], intermittent
catheterization may be preferable to long-term indwelling urethral catheter.
 CANDIDURIA
• Increasingly common complication of indwelling catheterization, particularly
for patients in the
intensive care unit,
broad-spectrum antimicrobial drugs,
underlying diabetes mellitus.
• >50% of isolates have been found to be non-albicans species.
• Removal of the urethral catheter results in resolution in more than one-third
of asymptomatic cases.
• Treatment of asymptomatic patients does not appear to decrease the
frequency of recurrence of candiduria.
• And so Therapy is recommended in symptomatic cystitis or pyelonephritis and
for those who are at high risk for disseminated disease.
• High-risk patients include those with neutropenia, those who are undergoing
urologic manipulation, those who are clinically unstable, and low-birth-weight
infants.
• Fluconazole (200–400 mg/d for 7–14 days) is the first-line regimen for Candida
infections of the urinary tract. For Candida isolates with high levels of
resistance to fluconazole, oral flucytosine and/ or parenteral amphotericin B
are options.
THANK YOU