URINARY TRACT

INFECTIONS
Definitions

Bacteriuria

• Frequently used term; meaning bacteria in

the urine

• Can be ascertained by quantifying the

bacteria in voided urine or in urine
obtained via uretheral catherization
— Significant Bacteriuria
- Indicates that number of bacteria in the voided
urine exceeds the number that can be expected
from contamination from the anterior urethra (i.e,
≥ 105 bacteria/ml)

— Asymptomatic Bacteriuria
- Refers to significant bacteriuria w/o symptoms
- Affecting mostly women in old age groups
Localization:
A.) Lower Urinary Tract

— CYSTITIS

— URETHRITIS

- A syndrome involving dysuria, frequency,

urgency & suprapubic tenderness
B.) Upper Tract Infection
- are acute pyelonephritis, prostatitis,
intrarenal & perinephric abscess
- characterized by flank pain or
tenderness, fever and often associated with
dysuria, urgency & frequency
- however, these symptoms may occur
w/o infection. i.e renal infection or renal
calculus
Uncomplicated UTI
- refers to the infection in structurally and
neurologically normal urinary tract

Complicated UTI
- refers to infection w/ functional or
structural abnormalities (including individually
catheters and calculi)
Recurrences:
— Relapse of bacteriuria
- A recurrence of bacteriuria with the same
infecting microorganism that was present before
therapy was started and persisted

— Reinfection
- A recurrence of bacteriuria w/ a microorganism
different from the original infecting bacteriuria
- A new infection
UROSEPSIS
- a sepsis syndrome due to UTI

- Includes evidence of UTI plus 2 or more of the

following:

a. temperature : > 38 oC or less than 36 oC

b. heart rate : > 90 beats/ min

c. respiratory rate : > 20/min or PaCO2 > than

30mmHg
d. WBC : > 12,000/mm3, < than 4,000/mm3, or
> 10% band forms
 PATHOLOGIC
CHARACTHERISTICS
ACUTE PYELONEPHRITIS

- kidneys are enlarged especially severe

pyelonephritis

- with discrete yellowish abscess on the

surface

- pathognomonic feature historically

suppurative necrosis or abscess formation
within the renal substance.
CHRONIC PYELONEPHRITIS
- or chronic interstitial nephritis

- one or both kidneys contain gross scars due to

changes in pelvic wall w/ papillary atrophy and blunting

- its parenchyma shows interstitial fibrosis w/ an

inflammatory infiltrate of lymphocytes, plasma cells and
occasionally neutrophils

- tubules are dilated and contracted by atrophy of the

lining epithelium

- tubules contained colloids casts, sometimes called

thyroidization of the kidney
Papillary Necrosis

- Affecting the pyramids which replaced by

wedge-shaped areas of yellow necrotic tissue with
the base located at the cortico medullary junction
- as it progress – necrotic papilla may break
off proceeding a calyceal deformity

- once with infection, the collecting tubules

are filled w/ bacteria and polymorphonuclear
leukocytes.
PATHOGENESIS OF UTI
I. Ascending Route
- urethra is usually colonized with bacteria,
especially in women since it’s short & is in proximity
to the warm moist vulvar and perianal areas
- initially starts as colonization in vaginal
introitus and periuretheral area > invades bladder >
bacteria multiply and then pass up to the ureters
(more among with vesicoureteral reflux) then to the
renal pelvis and parenchyma
- colonization occurs in massage of the urethra
in women and sexual intercourse
 - condom use may heighten the traumatic effects

- catheterization of the bladder

- both diaphragm of monoxynal, 9 contraceptive

jelly in women and condom catheter in men may
predispose to infection and also spermicides due to
adherence of E.coli to vaginal epithetial cells.

- also with estrogen, as predisposing factor to

cause recurrent UTI among post-menopausal women due
to vaginal flora changes, its lacto bacilli is replaced by
coliform and other uropathogens
II. Hematogenous Route
- most common organism is staphylococcus
aureus, causing bacteriuria or endocarditis also
candida

III. Lymphatic Route

- involves the renal lymphatic once there is
increase pressure in the bladder can cause
lymphatic flow to the directed toward the kidney
CONDITIONS AFFECTING
PATHOGENESIS
— GENDER and SEXUAL ACTIVITY

- Sexual intercourse cause the introduction of

bacteria into the bladder – onset of cystitis
- Voiding after intercourse reduces the risk of
cystitis which promotes the clearance of
bacteria
- Male population – common source is due to
prostatic obstruction and also rectal intercourse
— Pregnancy
ASB in pregnancy is the presence of
>100,00 CFU/mL of the same uropathogen in
two consecutive midstream urine specimens or
≥100 CFU/mL of a single uropathogen in one
catheterized urine specimen. Symptoms
attributable to urinary infection should be
absent.
- 2 – 8 % are detected
- Usually asymptomatic but once reach the renal
pelvis develop pyelonephritis
— Due to decrease ureteral tone, decreased
ureteral peristalsis and incompetence of the
vesico ureteral valves
— Screen ALL pregnant women for asymptomatic
bacteriuriaonce, between the 19th to 17th week
age of gestation (AOG), preferably on the 16th
week AOG
—A standard urine culture of clean-catch
midstream urine is the test of choice in
screening for asymptomatic bateriuria
— Urinalysis is not recommended as an initial
screening test
Antibiotic Treatment

— Antibiotic treatment for asymptomatic bacteriuria is

indicated to reduce the risk of acute cystitits and
pyelonephritis in pregnancy as well as the risk of
low birth weight neonates and preterm infants

— Treatment with antibiotics should be initiated upon

diagnosis of ASB in pregnancy. Among the
antibiotics that can be used are nitrofurantoin (not
for near term), co-amoxiclav, cephalexin, cefuroxime,
fosfomycin, and TMP-SMX (not on the first and third
trimester) depending on the sensitivity results of the
urine isolate
— Duration of treatment will depend in the
antibiotics that will be used, but short-course
(seven days) treatment is preferred over single-
does regimens

— A follow-up urine culture should be done one

week after completing the course of treatment

— Monitoring should be done every trimester until

delivery
— Neurogenic Bladder Dysfunction

- In spinal cord injury, diseases like tables

dorsalis, multiple sclerosis, DM

- Due to interference with bladder innervation

— VESICOURETERAL REFLUX

- Common among children with anatomic

abnormalities of the urinary tract
- Some population, reflux disappears with
advancing age
- But need to have long-term follow-up – might
result to failure of renal growth and scarring
- Do retrograde psychopathy with contrast media
— Bacterial Virulence Factors

- E.coli strains O, K & H serogroups

- Due to its virulence genes, contains hairlike
proteinaceous surface appendages, fimbriae
which adheres to uroepithelial cells of the host.
E.coli produce also cytotoxins hemolysis and
aerobactin.
ETIOLOGY
1. E. coli = 80% causing acute infection
2. Proteus
3. Pseudomonas
4. Klebsiella
5. Enterbacter species
6. Staphylococci
a. Staphylococci Aureus
b. Staphylococci Saprophyticus
c. Staphylococci Epidermis

7. Candida
CLINICAL MANIFESTATIONS

1. fever, sometimes with chills

2. Flank pains
3. urgency
4. Frequency
5. Dysuria
6. Hematuria
a. Microscopic
b. Gross
DIAGNOSIS
A. Presumptive Diagnosis
a. Urinalysis – midstream urine with at least 10
leukolyte/mm3
b. Dipstick leukocyte esterase test
- rapid screening test for detecting pyuria
- WBC 10/mm3
c. Microscopic/gross hematuria
d. Proteinuria
e. gram-staining

B. CULTURE
 ACCEPTABLE METHOD FOR URINE
COLLECTION

1. Midstream clean catch

2. Catheterization
3. Suprapubic aspiration
MANAGEMENT OF UTI
- generally, must treat the infection

- for asymptomatic, must have two cultures

- fear of reinfection and complication
especially among DM and other
immunocompromised patients and also among
elderly patients
- for children with vesicoureteral reflux (if
congenital anomalies) can result to stunted growth
of the kidneys, scar formation but rarely renal
failure.
- and also pregnant women
- hospitalized patients especially with in
1. Hydration
- Produces rapid dilution of the bacteria and
removal of infected urine by frequent bladder
emptying

2. Acidification of urine pH
- Nitroformation may be used to lower pH 5.5
- Ascorbic acid – but form oxalate stones
- Cranberry juice
3. Analgesics
- With the word of phenazopyridine
hydrochloride (pyridium)

4. Antimicrobial Therapy
- Among patients with renal insufficiency – need
to modify the dosage according to creatinine
clearance especially aminoglycosides
 4 Patterns of response of
Bacteriuria to Antimicrobial
Therapy
1.Bacteriologic cure

-Defined as (–)urine cultures on hemotherapy

and during the follow-up period (usually 1 – 2
weeks)
2. Bacteriologic Persistence
a.) persistence of significant bacteriuria after
48 hours of treatment
b.) persistence of the infecting organism in low
numbers in urine after 48 hours

- this may occur when the infecting strain is

resistant to the urinary attained e.g. resistant
organism or because the levels of the drug are
inordinarily low e.g. not taking the medicine,
insufficient dosage, poor intestinal absorption or
poor renal excretion among renal insufficiency.
3. Bacteriologic Relapse
- usually occur 1 – 2 weeks after the cessation
of the drugs.
- also presence of structural abnormalities of
the urinal tract

- relapse indicates that the infecting

microorganism has persisted in the urinary tract
during the therapy

4. Reinfection
- after initial sterilization of the urine, reinfection
may occur – also called as super infection
 Classification and
Antimicrobial Therapy for
Different Groups
ACUTE PYELONEPHRITIS
- severely ill – hospitalization
- mild to moderate – may start oral therapy –
outpatient
- may start ampicillin or amoxicillin (for
gram positive cocci in chain and may use also first
generation cephalexin
- gram (–)bacillus first generation
cephalosporin are 35% resistant and also to
Trimethoprim – Sulfamethoxazole
 Empiric Treatment regimens for acute pyelonephritis
Antibiotics Dose, Frequency and
Duration
ORAL
Primary Ciprofloxacin 500 mg BID for 7-10 days
Ciprofloxacin extended release 1000mg OD for 7 days
Levofloxacin 250 mg OD for 7 – 10 days
750 mg OD for 5 days
Ofloxacin 400 mg BID for 14 days
Alternative Cefixime 400 mg OD for 14days
Ceftibuten 400 mg OD for 14days
Cefuroxime 500 mg BID for 14days
Co-amoxiclav (when GS growing 625 mg TID for 14days
gram-positive orgs)
 Empiric treatment regimens for acute pyelonephritis
Antibiotic Dose, Frequency and
Duration
PARENTAL (given until patient is afebrile)
Primary Ceftriaxone 1-2 g q24hours
Ciprofloxacin 400 mg q12 hours
Levofloxacin 250-750 mg q24 hours
Ofloxacin 200-400 mg q 12 hours
Amikacin 15 mg/kg BW q 24hours
Gentamicin +/- ampicillin 3-5 mg/kg BW q24 hours
Alternative Ampicillin-sulbactam (when GS 1.5 g q6 hours
shows gram-positive orgs)
Reserved for Etrapenem (if ESBL prevalence 1 g q24 hours
MDROs >10%)
Piperacillin-tazobactam 2.25-4.5 g q6-8hours
 - for hospitalized patient may use parenteral:

a) aminoglycosides
b) Piperacillin Tazobactam
c) 3rd Generation Cephalosporin
d) Carbapenems
e) fluoroquinolone

- within 48 hours if no bacteriologic response –

may change the drug and will be based to culture
and sensitivity once available
 - still with fever and patient still toxic –
further investigation in necessary by doing MRI to
rule-out renal abscess

- 14 days therapy remain standard and

prolonged treatment especially dealing renal
abscess plus drainage
LOWER URINARY TRACT INFECTION
— short – course therapy
- defined as 3 or fewer days for treatment
- advantage is lesser cost, better
compliance, fever side effects and less intensive
selective pressure for the emergence of resistant
organism in gut, uretheral or vaginal flora
- need to have higher dose especially
single dose therapy. (E.g. 3 grams of Amoxicillin) –
still there is 57% failure rate
 - Short-course therapy may last for 3 days
therapy
- effective among fluoroquinolones than β-
lactam antibiotics
- if no response – need to have urine
culture
FUNGAL INFECTIONS

- Candida infection occur among patients

with in dwelling catheter
- may give Fluconazole 200mg / day for
7 days
 Can biomarkers help determine
which patients can be treated as
outpatients, or which patients will
have adverse outcomes?
ØBiomarkers (procalcitonin, mid-regional
pro-atrial natriuretic peptide, C-reactive
protein) are NOT recommended since
they are not clinically useful in
determining the need for admission or in
predicting adverse outcomes such as
recurrence and prolonged hospitalization.

ØStrong recommendation, Low quality of

evidence.
Summary of Evidence
— A multicenter, prospective, observational study
in 12 emergency departments in France
evaluated 582 consecutive patients to assess
the effectiveness of procalcitonin (PCT), mid-
regional pro-atrial natriuretic peptide (ANP), and
C-reactive protein (CRP) measurements in
guiding emergency physicians on deciding if a
patient with acute pyelonephritis should be
admitted to the hospital.

— Performance characteristics were tested for

various cut-offs of CRP, PCT and ANP
— The likelihood ratios were not clinically relevant
whatever the biomarker or threshold

— The study concluded that none of these three markers

could reliably help physicians in their decision making
process.

— Another French study evaluated the discriminatory

power and predictive accuracy of procalcitonin for
adverse outcomes in patients with acute
pyelonephritis.
— Nineteen percent of 58 patients analyzed had
adverse medical outcomes which include:

o A perceived need for hospitalization: presence of

concomitant systemic inflammatory response and
organ dysfunction, urgent urologic surgical procedures
related to pyelonephritis, evidence of renal abscess,
admission to intensive care

o Subsequent hospitalization

o Pyelonephritis-related death”
— Procalcitonin varied widely, and although the
median level was higher in patients with adverse
medical outcomes compared with those without
adverse medical outcomes, the difference was not
statistically significant (0.51 ng/mL vs. 0.08 ng/mL,
p=0.07).

— There was no useful threshold that could accurately

discriminate between the two groups.

— The utility of procalcitonin bacteremia was evaluated

in a prospective observational multicenter cohort
study of 581 adults with febrile UTI.
— A single procalcitonin level >0.25 ug/L had the best
diagnostic performance in predicting the presence
of bacteremia, 95% sensitivity (95% CI 89%, 98%),
specificity 50% ( 95% CI 46%, 55%).

— The use of this biomarker decreased the number of

blood cultures taken by 40% but still enabled
identification of 94% to 99% of patients with
bacteremia. This translated to cost-savings for the
patients

— However, blood cultures are recommended to be

taken prior to the initiation of antibiotics. Waiting for
the results of procalcitonin levels to determine
which patients would require blood cultures would
result in inappropriate delay in treatment.
— The use of C-reactive protein as a marker of
prolonged hospitalization and AUP recurrence was
analyzed in 202 consecutive patients in six different
institutes in South Korea.

— Simple Logistic regression analysis revealed that

there was a significant correlation between the CRP
level at discharge and recurrence of acute
pyelonephritis (p<0.001)
— There was greater incidence of recurrence in patients
with CRP >4mg/dL at discharged compared with
patients with CRP <4mg/dL (p=0.045).

— Patients with a maximal CRP of >15mg/dL during

admission, on the other hand, had longer
hospitalization stays compared to patients with
maximal CRP <15 mg/dL (p<0.001)

— The need for intravenous antibiotic therapy in these

patients was greater (p< 0.001)
— The clinical utility of knowing that patients with
certain CRP levels have a higher recurrence rate or
have a prolonged hospitalization remains unclear.

— Because of the limited availability, limited clinical

utility, and the cost of these biomarkers, especially
in resource limited settings, routine use of
biomarkers in the management of AUP is not
recommended