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Urinary tract infection and

pyelonephritis
Definitions
Terminology Definition

UTI an inflammatory response of the urothelium to bacterial invasion that is usually


associated with bacteriuria and pyuria

Bacteriuria presence of bacteria in the urine

Pyuria the presence of white blood cells (WBCs) in the urine,


indicative of infection and/or an inflammatory response of the urothelium to
bacteria, stones, an indwelling foreign body, or other conditions that can
contribute to pyuria.
Definitions: Infections by presumed origin
Terminology Definitions

Cystitis clinical syndrome of dysuria, frequency, urgency, and occasionally suprapubic


pain.

Acute pyelonephritis clinical syndrome of chills, fever, and flank pain that is accompanied by
bacteriuria and pyuria, a combination that is reasonably specific for an
acute bacterial infection of the kidney.
Chronic pyelonephritis shrunken, fibrosed kidney, diagnosed by morphologic, radiologic, or
functional evidence of renal disease that may be postinfectious but is
frequently not associated with current (active) UTI
Xanthogranulomatous rare form of chronic pyelonephritis often associated with stone disease and
pyelonephritis characterized by destructive replacement of normal renal parenchyma with
granulomatous inflammation;
it is associated with ipsilateral loss of renal function
Definitions
• UTIs may also be described in terms of the
anatomic or functional status of the urinary tract
and the health of the host.

• Uncomplicated- structurally and functionally


normal Urinary tract, Healthy patient

• A complicated infection - associated with factors


that increase the chance of acquiring bacteria
and decrease the efficacy of therapy

• The urinary tract is structurally or functionally


abnormal, the host is compromised, and/or the
bacteria have increased virulence or antimicrobial
resistance
Pathogenesis
• UTI is a result of interactions between uropathogen and the host

• Successful infection of the urinary tract is determined by:

Virulence factors of the bacteria

UTI

Inadequacy of host defense mechanism


Inoculum size
Pathogenesis: Route of Infection
ASCENDING ROUTE Most common
Enter the UT from bowel and in reservoir through
urethra into bladder
Increased: Gram Negative bacteria , Pregnancy,
Ureteral obstruction, Increased lower urinary tract
pressure

Hematogenous Route occasionally secondary kidney infection in patients


with Staphylococcus aureus bacteremia originating
from oral sites or with Candida fungemia.
Increased in obstruction

Lymphatic Route adjacent organs via lymphatics may occur in unusual


circumstances, such as a severe bowel infection or
retroperitoneal abscesses
Pathogenesis: Urinary Pathogens

• Most UTIs are caused by facultative anaerobes usually originating


from the bowel flora

• Uropathogens such as Staphylococcus epidermidis and Candida albicans


originate from the flora of the vagina or perineal skin

• Uropathogenic E. coli (UPEC) is by far the most common cause of


UTIs, accounting for 85% of community-acquired and 50% of
hospital-acquired infections.
Epidemiology

Source:McLellan, L. K., & Hunstad, D. A.


(2016). Urinary Tract Infection: Pathogenesis
and Outlook. Trends in molecular
medicine, 22(11), 946–957.
Urologica
l
infections

fluoroquinolone resistance is
a hallmark phenotype among
ST131 isolates
Pathogenesis of
urinary tract
infections

Source:McLellan, L. K., & Hunstad, D. A. (2016). Urinary


Tract Infection: Pathogenesis and Outlook. Trends in
molecular medicine, 22(11), 946–957.
Early Events in Uropathogenic E. coli Pathogenesis

(1) UPEC colonization of the periurethral and vaginal tissue as well as the urethra (mediated by pili)

(2) ascending infection into the bladder lumen and within the urine (mediated by FimH-mediated binding

(3) adherence to the surface urothelium and interaction with the bladder epithelial cell defense mechanism;

(4) biofilm elaboration

(5) invasion and replication by forming bladder Intracellular Bacterial Communities (IBCs), in which
quiescent intracellular reservoirs (QIRs) can form and stay dormant in the underlying urothelium

(6) in some cases, renal colonization and host tissue damage with high risk for sepsis
Clinical and Pathogenesis relation
• an increased epithelial receptivity for E. coli on the introital,
urethral, and buccal mucosa that is characteristic of women
susceptible to recurrent UTIs and may be a genotypic trait

• susceptibility to recurrent UTI was increased by the lowered


estrogen levels found in the postmenopausal women and that
estrogen replacement decreased uropathogenic bacterial
colonization and the incidence of UTI
Natural Defenses of the Urinary Tract
Site Mechanism

Periurethral and urethral region Normal flora such as lactobacilli, coagulase-


negative staphylococci, corynebacteria, and
streptococci that form a barrier against
uropathogenic colonization

Urine Flow of urine and voiding – number 1 defence


Reasons: High Osmolality (low ph), High urea,
Uromodulin/Tamm- Horsfall protein binds
(uroplakin receptors of the urothelium),
Lactoferrin (scavenges Fe)
Bladder Factors ability of bladder to empty,
innate and adaptive immunity
Exfoliation of epithelial cell
Alterations in Host Defense Mechanisms
1. Obstruction:
• Stasis contributes to growth and adherence of bacteria
• Can make minimal episodes of cystitis or pyelonephritis- Life
threatening
2. Vesicoureteral Reflux
• Paeds- Children with high grade reflux and UTIS usually develop
progressive renal damage.
• Manifested by renal scarring, proteinuria and renal failure
• Adults on high storage pressure/stasis and concurrent UTIS
Alterations in Host Defense Mechanisms
3. Underlying disease- primary renal papillay damage in DM, sickle cell,
hypoK, HypoP04, gout
4. Diabetes mellitus:
• DM women have a higher incidence of asymptomatic bacteriuria and symptomatic UTIs
• Patients predisposed to severe infection
• Higher incidence of resistant pathogens
5. HIV - UTIs are fivefold more prevalent
Other Conditions That Increase Risk of Urinary
Tract Infections
• Renal

• Menopause

• Pregnancy

• Spinal Cord Injury with High Pressure Bladders


• Of all patients with bacteriuria, no group compares in severity and morbidity with those who
have SCI
Assessment: Signs AND Symptoms

Cystitis Dysuria, Frequency,,urgency +/-


Fever +/-

Pyelonephritis fever, chills, flank pain, and costovertebral-angle


tenderness
Assessment
Laboratory investigations
• Leukocyte esterases - Positive in pyuria
• Nitrites- bacteria reduce dietary nitrates.All enterobactericae produce
nitates
• More reliable L.E + Nitrites + > 100,000 Colony forming Units/ml
• Dipstick : Positive nitrites or positive leukocyte esterase and blood on
a dipstick most accurately diagnose a UTI (Little et al., 2009)
• Automated: Urinalyisis and Culture
Imaging: Who do you image
• Most men
• Compromised hosts
• Febrile infections,
• Signs or symptoms of urinary tract obstruction
• failure to respond to appropriate therapy
• pattern of recurrent infections suggesting bacterial persistence
Indications of Radiologic interventions
Mechanism Of Action
Mechanism Of Action
• Acute pyelonephritis
• Emphysematous Pyelonephritis
• Acute Focal or Multifocal Bacterial Nephritis
Acute Pyelonephritis
• pyelonephritis is defined as inflammation of the kidney and renal
pelvis

• Clinical Presentation:
Abrupt onset of chills, fever (100.3F), and unilateral or bilateral flank or
costovertebral angle pain and/or tenderness

On physical examination, there often is tenderness to deep


palpation in the costovertebral angle
Laboratory DIagnosis

• CBC: Leukocytosis, predominance neutrophils

• Inflammatory markers: erythrocyte sedimentation rate, C-reactive protein


(elevated)

• Urine cultures are positive, but about 20% of patients

• have urine cultures with fewer than 105 CFU/mL and therefore

• negative results on Gram staining of the urine

• Blood culture – Positive only in 25%


Imaging
GUIDELINES
Perform US to rule out urinary
tract obstruction

CT scan for patient who


complicate or remain febrile in 72
hrs

Pregnant women- US and MRI are • Ultrasound findings- focal parenchymal swelling,
options echogenicity increased/decr
Imaging
Acute pyelonephritis: Management

• Divided into

(1) uncomplicated infection that does not warrant hospitalization

(2) uncomplicated infection in patients with normal urinary tracts who


are ill enough to warrant hospitalization for parenteral therapy

(3) complicated infection associated with hospitalization,


catheterization, urologic surgery, or urinary tract abnormalities
uncomplicated infection that does not warrant
hospitalization
Indications for Admission
• high fever,
• high WBC count,
• vomiting, dehydration, evidence of
sepsis
• has complicated pyelonephritis
• or fails to improve during the
initial outpatient treatment period,
• a parenteral antibiotic is
recommended
• Hospitalization, IV fluids, and
antipyretics are required.
Subsequent Management Unfavorable Response to Therapy

• Re-evaluate
• Patients with complicated
• Repeat urine cultures, blood
pyelonephritis and positive blood cultures
• If febrile after 72 Hrs- CT is most
cultures should be treated with
helpful for ruling out
parenteral therapy until clinically obstruction and identifying
renal and perirenal infections
stable.

• Transition to oral to achieve 10-12 • Other options- VCUG,


cystoscopy, radionuclide test for
days differentials
EAU Guideline
Treatment in Women
Differential Diagnosis

• Acute appendicitis

• diverticulitis, and

• pancreatitis can cause a similar degree of pain, but the location

• of the pain often is different, Urinalysis normal


Emphysematous Pyelonephritis

• a urologic emergency characterized by an acute necrotizing


parenchymal and perirenal infection caused by gas-forming
uropathogens.

• Common in diabetics (95% of the cases- Singh)


• Women > Men
• many patients have urinary tract obstruction associated with urinary
calculi or papillary necrosis and significant renal functional
impairment. (Risk in UTO- 25%- 40%)
• The overall mortality rate 19%- 43%
Clinical Presentation

• classic triad of fever, vomiting, and flank pain

• Nearly all cases in adults, diabetics

• Non diabetics- have ureteral obstruction, not extensive disease

• An acute attack , some cases preceded with chronic infection

• E. coli is most commonly identified. Klebsiella and Proteus spp. are less common
Radiologic Findings
• The diagnosis is established
radiographically

• Tissue gas that is distributed in the


parenchyma may appear on
abdominal radiographs as mottled
gas shadows over the involved
kidney

Sonography will show intra renal gas


Radiologic Findings: CT scan
• CT is the imaging procedure of
choice
• Defines the extent of the
emphysematous process and guides
management

• An absence of fluid in CT images or


the presence of streaky or mottled
gas with or without bubbly and
loculated gas appears to be
associated with rapid destruction of
renal parenchyma and a 50% to
There is air within and surrounding the left 60% mortality rate
kidney.
Classification of EPN

Ubee SS, McGlynn L, Fordham M. Emphysematous pyelonephritis. BJU Int. 2011


CT classification
CT Classification
Radiological Staging

Accumulation of gas (arrow


heads bilaterally)
Patient with polycystic kidney
disease
Management- EPN – Urologic emergency

• Sepsis fluid resuscitation, glucose and electrolyte management, and


broad-spectrum antimicrobial therapy are essential
• Ureteral obstruction is alleviated by a percutaneous nephrostomy
tube or a stent
• Nephrectomy - only in extensive diffuse gas with renal destruction

• Poor Prognostic factors- (INCREASED MORTALITY)


• Hypoalbuminemia, Thrombocytopenia, Altered mental state,
polymicrobial infection, Indication for dialysis, Shock at initial
presentation
• Ubee SS, McGlynn L, Fordham M.
• Emphysematous pyelonephritis. BJU Int. 2011
Acute Focal or Multifocal Bacterial Nephritis
• DEFINITION - an uncommon, severe
• form of acute renal infection in which a heavy leukocyte infiltrate is
• confined to a single renal lobe (focal) or multiple lobes (multifocal)

• Clinical presentation- Similar to AP, more severe

• Half of the patients diabetic, sepsis is common


Acute Focal or Multifocal Bacterial Nephritis

• Note irregular midpole mass (M) of slightly higher echo texture than surrounding normal renal parenchyma.
• (B) Contrast medium–enhanced computed tomography scan demonstrates a wedge-shaped area of low density
(arrows) in the middle portion of the left kidney. The findings resolved after antimicrobial therapy.
Management
• Acute bacterial nephritis probably represents a relatively early phase
of frank abscess formation

• Treatment includes hydration and IV antimicrobial agents for at


least 7 days, followed by 7 days of oral antimicrobial therapy

Failure to respond to antimicrobial therapy is an indication for


appropriate studies to rule out obstructive uropathy, renal or perirenal
abscess, renal carcinoma, or acute renal vein thrombosis
RENAL ABSCESS
• is a collection of purulent material confined to the renal parenchyma
• Risk factor: renal disease, Complicated UTIs associated with stasis,
calculi, pregnancy, neurogenic bladder, diabetes mellitus
• Typically gram negative infection
• Laboratory- Typically leukocytosis
• Urine and abscess culture- identical culture 15%
• blood and abscess- 13% identical culture rate
Renal Abscess: Imaging

• Ultrasonography and CT distinguish abscess from other inflammatory


• renal diseases

An echo-free or
low-echodensity space-occupying lesion with increased
transmission
is found on the ultrasound image
Renal Abscess: CT scan

• Depends on age
and severity of
abscess
• Initially, CT shows
renal enlargement
and focal, rounded
areas of decreased
attenuation
Renal Abscess: CT scan
obliteration of adjacent tissue planes
thickening of the Gerota fascia,
a round or oval parenchymal mass of low
attenuation, and a
Surrounding inflammatory wall of slightly higher
attenuation that forms
a ring when the scan is enhanced with contrast
material
Renal Abscess: Management
• Based on Size
• Less than 3cm – IV antibiotics
• 3-5cm- IV antibiotics, follow clinical course and radiographically
• > 5cm- percutaneous drainage, can be multiple

• CT- or ultrasound-guided needle aspiration may be necessary


to differentiate an abscess from a hypervascular tumor.
Perinephric Abcess

• extends beyond the renal capsule but is contained by Gerota fascia

• RESULTS FROM

I. from rupture of an acute cortical abscess into the perinephric space

II. or from hematogenous seeding from sites of infection.

At risk DM (1/3rd of patients) and Pyonephrosis with a calculus


Clinical presentation
• Suspect in a patient with UTI and
1. abdominal or flank mass or persistent
2. fever after 4 days of antimicrobial therapy.

• PA are commonly seen concomitantly with renal abscesses

• leukocytosis, elevated levels of serum creatinine, and pyuria in more


than 75% of cases
• Data inadequate on urine vs abscess vs blood culture

• CT is particularly valuable for demonstrating the primary abscess.


Imaging
• CT scan modality of choice
• Has helped reduce mortality
Management: Perinephric Abcess
• 1. Prompt IV antibiotics
• - An aminoglycoside + antistaphylococcal agent, such as methicillin or
• oxacillin, should be started immediately

• small perinephric abscesses (<3 cm),


• antibiotics alone can appropriately treat immune-competent patients
Management: Perinephric Abcess
• Unlike in renal abscesses, early drainage of abscesses greater than 3
cm in diameter is recommended

• it is best to drain the perinephric abscess first and correct the


underlying problem or perform a nephrectomy when the
• patient’s condition has improved

• Meng’s series of 11 patients with abscesses greater than 11 cm had


a roughly 33% need for nephrectomy
Perinephric Abscess Versus Acute
Pyelonephritis
• Greatest Obstacle to treatment of PA is delay in diagnosis
APN PA

Duration of symptoms Less than 5 before Longer than 5 days


hospitilisation

Fever Resolved by day 4 At least 5 days, median 7


days
References
• Campbell 12th edition
• EAU 2020 guidelines
• Huang JJ, Tseng CC. Emphysematous pyelonephritis:
clinicoradiological classification, management, prognosis, and
pathogenesis. Arch Intern Med. 2000 Mar 27;160(6):797-805
• Ubee SS, McGlynn L, Fordham M. Emphysematous pyelonephritis.
BJU Int. 2011 May;107(9):1474-8.

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