Urinary tract infections

Urinary Tract Infections
DR.TARIK
ELDARAT
MD UROLOGIST

Friday, October 18, 2013

Today’s Goals







Be able to define the various types of UTIs
Describe the classic signs of pyelonephritis
Be able to determine if a urine culture is positive
Know the types of imaging needed and who needs
imaging
Explain why we care so much about early diagnosis and
prompt treatment


Definitions








UTI—inflammatory response of the urothelium to
bacterial invasion.
Uncomplicated—Healthy patient with normal urinary
tract.
Complicated—compromised patient or one with a
functional or structural abnormality.
Recurrent
– Reinfection—infection from different bacteria outside the urinary
tract.
– Persistent—focus from within the urinary tract that is never
eradicated.


Bacteriuria: the presence of bacteria in the urine
Significant bacteriuria: 105 organism or more per milliliter
Pyuria: the presence of white blood cells in urine
Pyuria with 5 or more cells per microscopic
high-power field: reliable indicator of UTI
The absence of such pyuria does not reliably
exclude UTI


Pyuria alone=inflammation
 Bacteriuria without pyuria=colonization
 Epithelial cells=contamination


The normal urinary tract is sterile
for many reasons:
Eradication of bacteria by urinary and mucous
flow:
secretory peptides target cytoplasm of
bacteria
Urothelial bactericidal activity
Urinary secretory IgA
Blood group antigens in secretion alter
bacterial adhesion

Defenses


Primary Defense
– Flow of Urine
– Voiding



Secondary Defense
–
–
–
–
–

Lactoferrin
pH
IgA
IL-6
IL-8

– Tamm-Horsfall

Classification
Isolated—first infections or those isolated by 6 months(3040% of women).
 Unresolved—insufficient treatment
– Resistance
– Development of resistance
– Two species one is resistant
– Rapid reinfection before completion of therapy on
initial organism
– Azotemia(poor concentration of drug)
– Papillary necrosis + azotemia
– Staghorn Calculi(mass and concentration of bacteria
too great)


Epidemiology









7 million office visits annually(1.2% female, 0.6% male)
Prevalence increases with hospitalization, disease, number
of infections,
Susceptible females—2 infections in 6 months = 66%
chance of developing infection in the next 6 months.
Prophylaxis changes the time to recurrence not the chance
of recurrence.
Pregnancy increases the clinical acuity of infections.


Pathogenesis


Ascending—predominant route
– Impairment of peristalsis enhances
infection(endotoxin from G- Bacteria,
pregnancy, obstruction)
– Pelvic Pressure enhances
infection(obstruction, VUR)

Hematogenous—rare
 Lymphatic—very rare(RP abscess)


Pathogens


Nosocomial
– E. Coli—50%
– Klebsiella
– Enterobacter
– Citrobacter
– Serratia
– Pseudomonas
– S. epidermitis




Community-Acquired
– E. Coli—85%
– Proteus
– Klebsiella
– E. faecalis
– Staph.
Saprophyticus(10%
of young sexually
active females)

Community-Acquired UTI
E.coli

S.epi &
gm - enterics
Enterococcus
Proteus
K.pneumoniae S.saprophyticus

Nosocomial UTI
catheter associated
Short Term

Long Term
E.coli

Enterococcus

Enterobacter

E.coli

Proteus

Candida
Proteus

Providencia
Morganella

S.aureus
Pseudomonas


Pseudomonas

Causative organisms
Gram +ve: Enterococci, Staphylococcus
saprophyticus.
 Gram –ve: Escherichia coli, Proteus
species, Pseudomonas aeruginosa,
Klebsiella strains.
 Also: Mycobacterium tuberculosis



Escherichia coli


E. coli (serotypes: 02, O4, O6) which are
fimbrinated strains adhering to uroepithelial cells, leading to colonization and
infection is the commonest cause of urinary
tract infections.


Gram negative bacilli
Pseudomonas, Proteus, and Klebsiella
infections often follow catheterization and
gynecological surgery (nosocomial
pathogen).
 Infection with proteus may be complicated
by phosphate stone formation as it is urea
leads to alkaline pH.



S. saprophyticus


Infection more common in young women.


What parts of the urinary
tract can get infected?
Urethra - Urethritis
Urinary bladder – Cystitis
Ureters – Ureteritis
Kidneys - Pyelonephritis


Incidence
1-3% of all GP consultations
 5% of women each year with symptoms. Up
to 50% of women will suffer from a
symptomatic UTI during their lifetime.
 UTI in men is much rarer
 A proportion of patients may be
symptomatic in the absence of infection called 'urethral syndrome'


What are the signs and symptoms
of UTI?

Cystitis
Frequency
Urgency
Dysuria – painful voiding
Pain or discomfort in
suprapubic or perineal
area or lower back
Cloudy or foul-smelling
urine

Causes


The most common cause is bacterial infection
– Eschericia coli is the pathogen in 70% of
uncomplicated case of lower urinary tract infections.
– Other organisms include Proteus mirabilis, Klebsiella
pneumoniae, Staphylococcus saprophyticus,
Staphylococcus aureus and Pseudomonas species.




Urethral Syndrome -not associated with any
infection
Rarely kidney or bladder stones, prostatism,
diabetes

Prevention
Drinking plenty of fluids helps prevent
cystitis in the first place.
 If cystitis follows sexual intercourse, some
advise passing urine soon after to try and
prevent it.
 There is no evidence to suggest a link
between lower urinary tract infection and
use of bath preparations


Beware!
Pregnant
 Under age 12
 Males
 Systemically ill (fever, sickness, backache)
 Catheterised patients
 Kidney or bladder stones


Investigation


Urine dipstick
– can be done in the surgery and will be positive for nitrates and
leucocytes (leukocyte esterase test). This helps to differentiate
those with UTI from the 50% with urethral syndrome.




Urine microscopy and culture reveals significant bacteruria
(usually >105 /ml).
Asymptomatic bacteruria
– is present in 12-20% of women aged 65-70 years and does not
impair renal function or shorten life so no treatment
– in 4-7% of pregnant women and associated with premature
delivery and low birth weight and always requires treatment.

Differential Diagnosis







Urethral syndrome
Bladder lesion e.g. calculi, tumour.
Candidal infection
Chlamydia or other sexually transmitted disease.
Urethritis
Drug induced cystitis (e.g. with
cyclophosphamide, allopurinol, danazol,
tiaprofenic acid and possibly other NSAIDs)

Complications and Prognosis







Ascending infection can occur, leading to development of
pyelonephritis, renal failure and sepsis.
In children, the combination of vesicoureteric reflux and
urinary tract infection can lead to permanent renal
scarring, which may ultimately lead to the development of
hypertension or renal failure. 12-20% of children already
have radiological evidence of scarring on their first
investigation for UTI.
Urinary tract infection during pregnancy is associated with
prematurity, low birth weight of the baby and a high
incidence of pyelonephritis in women.
Recurrent infection occurs in up to 20% of young women
with acute cystitis.

Management Issues - General
50% will resolve in 3 days without
treatment
 No evidence to support “drink plenty”
 It is reasonable to start treatment without
culture if the dipstick is positive for nitrates
or leucocytes.


Management Issues - General


Culture is always indicated in
–
–
–
–
–

Men
Pregnant women
Children
Those with failure of empirical treatment
Those with complicated infection

Self care


Drink slightly acid drinks such as cranberry
juice, lemon squash or pure orange juice
(poor trial evidence for this)



Try a mixture of potassium citrate available
from your pharmacist (little evidence but
widely recommended)

Principles of Antimicrobial Therapy
Treatment of UTI should result in sterile
urine.
 Antimicrobial levels in urine.
 Resistant clones present 5-10% of cases
with empiric treatment.



Antibiotics







Trimethoprim is an effective first line treatment.
Cephalosporins are as effective as trimethoprim
but more expensive and more likely to disrupt gut
flora.
Nitrofurantoin is as effective as trimethoprim but
more expensive and frequently causes nausea and
vomiting
The 4-quinolones (ciprofloxacin, norfloxacin,
ofloxacin) are effective in the treatment of cystitis.
To preserve their efficacy, they should not usually
be used as first line therapy

Antibiotics





3 days of antibiotic is as effective as 5 or 7 days
Single dose antibiotic results in lower cure rates
and more recurrences overall than longer courses.
In relapse of infection (i.e. reinfection with the
same bacteria), treatment with antibiotic for up to
6 weeks is recommended.

T re a tm e n t o f R e c u rre n t C y s titis
R e c u r r e n t C y s t it is

R e la p s e
S e e k o c c u lt s o u r c e o f in f e c t o n
U r o lo g ic e v a lu a t io n

R e in fe
D ia p h r a g m a n
C o n s id e r c h a n g in
m e th

T r e a t lo n g e r ( 2 - 6 w e e k s )

c t io n
d s p e r m ic id e
g c o n tr a c e p t iv e
o d

U r o lo g ic e v a lu a t io n n o t
r o u t in e ly in d ic a t e d

³ 3 U T I/y r

³ 2 U T I/y r

N o r e la t io n t o c o it u s

T e m p o r a lly
r e la t e d t o c o it u s

D a ily o r t h r ic e
w e e k ly p r o p h y la x is

P o s t c o it a l
p r o p h y la x is

P a t ie n t in it ia t e d t h e r a p y

Antibiotics for UTI in Pregnancy







Cephalosporins and penicillins are recommended
in pregnancy because of their long term safety
record
Nitrofurantoin is also likely to be safe during
pregnancy
Quinolones, Trimethoprim and Tetracyclines are
not recommended for use during pregnancy
Seven days of treatment is required.
Urine should be tested regularly throughout
pregnancy following initial infection.

Acute pyelonephritis
Fever
Nausea and vomiting
More pronounced malaise
Pain in the back
(+) CVA tenderness


Clinical Manifestations


Classic signs of cystitis
–
–
–
–
–
–
–
–
–



Enuresis
Frequency
Dysuria
Hesitancy
Suprapubic discomfort
+/- UTI signs
Chills
Nausea
Flank pain

Classic signs of pyelonephritis


In
older children and
adults

But… In Infants








Fever! Fever!!
Fever!!!
Lack classic signs
Irritabilty
Poor feeding
Vomiting
Diarrhea


Present in <1/2 of infants with UTIs

Risk factors


Female (30%:10%)
–
–
–

Shorter urethral length
Urethral opening close to the anus
Exposure to spermicide
» Has antimicrobial activity, disrupt the periurethral
flora content


Risk Factors: continued


Factors that prohibit
complete emptying of
the bladder
– Constipation
– cystocele, rectocele,
uterine prolapse,
urinary calculi, BPH





Estrogen deficiency
Oral antimicrobials
Immobility









Poor hygiene
Poor toileting habits
Fecal incontinence
Catheterization
Diabetes mellitus
Dehydration

Diagnosis
 Urine Collection

– Suprapubic
Aspiration
– Catheterized
specimen
– Voided
specimen

 Urinalysis

– Sensitive to
colonies of
30K/ml or less
– Bacteria seen
on microscopy
with no growth
may be vaginal
flora

Specimen collection
Samples should be collected before the start
of antibiotics.
 Transport within 2 h. if delay is suspected
then refrigeration at 4C or boric acid.
 Mid stream urine.
 Adhesive bags; in infants.



The Positive Culture


Suprapubic

– Any number of pathogens
– Should be completely sterile



Transurethral

– 103 colony forming units



Clean catch

– 105 colony forming units


Know the Adequacy of Your
Tests


“standard urinalysis”
– Urine dipstick
– Microscopy



“enhanced urinalysis”
–
–
–



Nitrites
Leukocyte esterase

Microscopy
Gram stain
84% sensitivity

Neither is sensitive enough to rule out UTI

15% of UTIs missed if culture not done

UTI - Who should be studied?


Acute pyelonephritis All febrile UTIs



Males of any age with first UTI
Girls younger than 3 years with first UTI
Girls older than 3 years with second UTI
Girls older than 3 years with first UTI with:
– Family history of UTIs
– Abnormal voiding pattern
– Poor growth
– Hypertension
– Abnormalities of urinary tract
– Failure to respond promptly to therapy






Clinical Manifestations
Feature

Cystitis Pyelonephritis Urosepsis

Dysuria,
frequency
Suprapubic pain

+

+ or -

+ or -

+

+ or -

+ or Ğ

Fever,
tachycardia,
hypotension etc.
CVA tenderness

-

+

+

-

+

+ or -

Duration of
symptoms (days)

1Ğ7

1Ğ2

<1 - 1

Imaging Techniques


Indications

– Evaluation of
obstruction
– Persistence of
fever after 5-6
days of treatment
– Diabetes
Mellitus
– TB, fungus, urea
splitting

A 3y/o boy has fever, shaking chills, and flank pain
consistent with a diagnosis of pyelonephritits.
Of the following, the BEST procedure to perform
immediately to define the anatomy of the genitourinary
tract is:
–
–
–
–
–

A. cystoscopy
B. intravenous pyelography
C. radioisotopic renography
D. renal ultrasonography
E. voiding cysourethrogram

Acute Uncomplicated Pyelonephritis in Women
 Mild-to-moderate illness
– Outpatient therapy
– Fluoroquinolone 7 - 14 days


Severe illness
– Hospitalization required
– Parenteral cephalosporin, fluoroquinolone or
aminoglycoside, after afebrile - oral therapy (10 - 14
day total)



Pregnancy - avoid fluoroquinolones

What determines a positive urine culture?
 Suprapubic?
 Transurethral?
 Clean-Catch?
Suprapubic
13-15% of end stage renal disease
Any number of pathogens
Due to Transurethral
103 colony forming units
Undiagnosed/Untreated UTI in childhood
Clean catch
 Why do we care so much about prompt diagnosis and
105 colony forming units
treatment?


27-64%

of those with pyelonephritis develop renal scarring

Emphysematous Pyelonephritis









pneumaturia
An acute necrotizing infection cause by gas
formation
Incidence: middle-aged or elderly
Diabetes (90%), or obstructive renal unit
Female-to-man = 6:1
Left kidney: 60%
Mortality: 20~80%

Emphysematous Pyelonephritis
/ Pathogenesis
Acute bacterial and fungal infection:
-- E. Coli: 70~90%
-- Klebsiella, Proteus, Clostridium and
Candida
 Gas in upper urinary tract:
-- iatrogenically via upper tract manipulation
-- fistula to bowel
-- ascending infection


Emphysematous Pyelonephritis /
pathogenesis
Gas extension: renal and hepatic vein
 Diabetics predisposed to gas formation:
-- high glucose level throughout tissue
-- diabetic microangiopathic disease
-- immunodeficient-like state


clinical findings
Unilateral: 90%
 Clinical findings:
-- fever and pyuria: 80%
-- flank or abdominal pain: 70%


clinical findings


Huang et al:
-- 48 cases
-- 46 cases: diabetics
-- mortality: initial presentation
1). thrombocytopenia
2). acute renal insufficiency
3). Proteinuria
4). Mental status change
5). Shock
-- no affect: age, sex, site of infection and glucose
level

Radiological findings
CT: modality of choice
-- excellent sensitivity and precise
localization of gas
 Abdomen radiograph: poor sensitivity
(33%)


Management
Traditionally: requiring emergent nephrectomy
 Minimally invasive drainage: acceptable
-- equivalent success to surgery
 Release obstruction
 Quinolone therapy
 Huang: thrombocytopenia, acute renal
insufficiency, mental status change and shock
-- <2: percutaneous drainage + IV antibiotics
-- ≥2: emergency nephrectomy


Xanthogranulomatous
pyelonephritis
XGP: chronic suppurative atypical renal
parenchymal infection
 : RCC, abscess and inflammatory disease
 Associated: renal calculi and chronic
urinary tract infection
 Majority involve: non-functional kidney


XGP / Incidence
0.6% of all surgically proven renal infection
 Women : men = 4:1
 More commonly in diabetics
 5th ~ 7th decades
 Almost always unilateral


XGP / Pathogenesis
Not been elucidated
 Play a role:
-- urinary tract anomalies, obstruction, chronic
infection, renal ischemia, immunodeficiency and
abnormal lipid metabolism
 Diagnosis: made by histological examination of
surgically removed kidney
 Characteristic: foamy macrophage
 Culture: proteus mirabilus (50%), E. Coli (20%)


XGP / Clinical findings
Quite nonspecific:
-- anemia, malaise, leukocytosis, pyuria, flank
pain or flank mass …
 Children: weight loss or failure to thrive
 Associated:
-- renal calculi: 75%
-- CPN: 78%


XGP / Radiological findings
Renal ultrasound: hypoechoic mass
 Advent CT: accurate with sensitivity (90%)
-- poor enhancing mass, thickened
Gerota’s fascia


XGP / Management




Absolutely no medical therapy
Open surgical nephrectomy: standard care
XGP kidney: extension to hilium and contiguous
organ

Treatment


Cystitis—3 Days
– 7 Days if duration of
symptoms, Diabetes, age
greater than 65, or
pregnancy



Pyelonephritis
– Women
» 7 days uncomplicated
without sepsis
» Inpatient 10-14 days




Comlicated Pyelonephritis
– 14-21 day course



Prophylaxis
– Endocarditis—Amp/Gent
or Vanc/Gent
– Indwelling catheter—2
Doses(prior susceptibility)
– Catheter removal—preop
and 72 hours after
– TURP—Pre and Post Op

Candidates for Prophylaxis
Women with ≥ 3 symptomatic uncomplicated
infections per 12 months
 Pregnant women with asymptomatic
bacteriuria or previous symptomatic UTI is
pregnancy
 Men with recurrent UTIs


Prostatitis

Prostatitis: classification



Acute vs. chronic vs. prostatodynia
Source of infection
– Ascending urethral infection, urinary reflux, extension
of rectal infection, or hematogenous spread



Bacterial
– E. coli, Proteus, Klebsiella, Pseudomonas, enterococci,
Chlamydia, Ureaplasma



Other agents
– Viral, fungal, and Trichomonas

Prostatitis: classification
Bacteriuria

Localized Inflammatory Abnormal Systemic
prostate
response
illness
prostate
infection
exam

Acute
bacterial
prostatitis

+

+

+

+

+

Chronic
bacterial
prostatitis

+

+

+

-

-

-

-

+/-

+/-

-

Prostatodynia

Prostatic massage



AVOID IN ACUTE PROSTATITIS
4 tube approach
–
–
–
–

VB1: urethral urinary sample
VB2: bladder urinary sample
EPS: expressed prostate secretions
VB3: post-massage urinary sample
» >10 WBC/hpf abnormal
» >5,000 colonies/mm abnormal



2 tube approach

Acute bacterial prostatitis


History
– Lower urinary tract obstruction, perineal pain,
dysuria, and fever
– Systemic symptoms



Physical
–
–

Tender, warm, boggy, swollen prostate
Massage is NOT indicated in acute prostatitis

Acute bacterial prostatitis


Management
– Outpatient therapy
» Bactrim, ampicillin, or quinolone for 4 – 6 weeks
» Bedrest, analgesics, antipyretics, stool softeners

– Inpatient therapy
» Parental antibiotics: ampicillin and gentamycin
» Avoid urethral catheterization for retention
» Urology consult

Chronic bacterial prostatitis


History
– Bladder outflow obstruction
– Dysuria; perineal, low back, or testicular pain
– Hematuria, hematospermia, painful ejaculation



Physical examination
– Variable prostate exam



Relapsing UTI in men is the hallmark of chronic
bacterial prostatitis
– GNR most common; also Enterococcus and S. saprophyticus

Chronic bacterial prostatitis


Management
– Difficult to eradicate given poor penetration of
antibiotic into the non-inflamed prostate
– Bactrim and fluoroquinolones
» Doxycycline and macrolides second-line

–
–
–
–

Prolonged treatment required
Recheck prostatic fluid after treatment
Alpha-blockers to reduce symptoms
Suppressive therapy

Prostatitis: complications
Renal parenchymal infection
 Bacteremia
 Prostate abscess


– Immunocompromised
– FB; obstruction


Prostatic stones
– Nidus for persistent
infection

Prostatodynia


History
– Persistent pelvic, suprapubic, infrapubic, scrotal,
inguinal, or perineal pain
– Lower tract obstruction and dysuria
– Absence of systemic symptoms





Physical exam usually unremarkable
No bacteria identified and no evidence of
inflammation present
Limited course of antibiotics, alpha blockade

Urinary tract infections

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