Transcript UTI

UTI
梅健泰
Ref.: Management of Urological
Emergencies, 2004, Taylor & Francies
UTI - DEFINITIONS
• Bacteriuria :the presence of bacteria in the urine from upper and
lower urinary tract sources with the presence or absence of both
pyuria and symptoms.
• Urinary tract infection (UTI) : occurs when a microbial agent, usually
bacterial, invades and colonizes the urinary tract.
– Uncomplicated UTIs (simple UTIs) : in a structurally and
functionally normal urinary tract, when the patient is not pregnant,
and when there is no history of recent antimicrobial use.
• eg. most isolated or recurrent lower UTIs and acute pyelonephritis
in female patients.
• Uncomplicated pyelonephritis, as an example, accounts for approximately
25% of all UTI-related admissions for inpatient treatment.
– Complicated UTIs : in a structurally and/or functionally
abnormal urinary tract.
• eg. secondary to urinary tract catheterization, urolithiasis, obstructive
uropathy, instrumentation, diabetes mellitus, pregnancy, immunosuppression
and congenital or secondary variations of urinary tract anatomy such as
prune belly syndrome, ileal conduits and bladder augmentation
UTI - INCIDENCE
• Female : Male = ~30:1
• Young children : M > F ( up to approximately 6 months of
age).
• In female : the incidence of UTIs increases with
advancing age.
– Approximately 1% of girls 5-15 years of age (bacteriuria).
– 5% in early adulthood (bacteriuria).
– Up to 30% between 20 and 40 years :experience an acute
bacterial UTI requiring treatment.
• Approximately 20% of women and 10% of men over 70
years of age will have bacteriuria upon culture of their
urine.
UTI - PATHOGENESIS
• Ascending route : most commonly,
bacteria enter the bladder via the urethra.
– Large bowel commensal organisms colonizing
the perineum, the perianal region
– the prepuce in the male
• Hematogenous and lymphatic
pathways : far less common, the spread of
bacteria from adjacent organs.
RISK FACTORS FOR URINARY TRACT INFECTION
•
Host factors
–
•
Factors specific to females
–
•
urinary stasis, local trauma, abnormal urinary tract anatomy and function, diabetes mellitus,
immunosuppression, debility, poor hygiene and aging.
deficient estrogen status and short urethral length.
Mechanical and other factors mediate the ability of the enterobacteria to colonize,
invade and damage the urinary tract.
–
In women
•
–
Elderly patients have an increased incidence of asymptomatic bacteriuria and UTI
•
•
external urinary drainage devices such as indwelling urethral catheters, suprapubic catheters
and nephrostomy drainage tubes.
Dysfunctional voiding in the male
–
•
reduced urogenital estrogen, reduced nutritional status, an inability to maintain body homeostasis,
poorer bowel function, increased comorbidities and a greater incidence of dysfunctional voiding.
Foreign bodies - breaching natural defense mechanisms
–
•
sexual intercourse, especially with a new partner, unusually vigorous intercourse, delayed postcoital
micturition, history of previous UTIs, and the use of spermicide and contraceptive diaphragms.
high voiding pressures and grossly elevated residual volumes
Augmentation or substitution of the lower urinary tract with bowel segments
DM & UTI
•
•
A common multisystem disease with potentially serious effects on
urinary tract anatomy and function.
Complications
– diabetic nephropathy, papillary necrosis, renal artery stenosis, and diabetic
cystopathy.
•
•
•
•
•
Bacteriuria is twice as common in glycosuric and diabetic patients.
A higher incidence of complicated upper and lower UTIs, such as renal
and perinephric abscesses, emphysematous pyelonephritis,
emphysematous cystitis, xanthogranulomatous pyelonephritis and fungal
infections.
A strong association with Fournier's gangrene, a life-threatening
synergistic infection.
Morbidity and potential mortality is greater in diabetic patients with UTIs.
Added risk of contrast nephropathy,
– especially in those patients with reduced renal function, dehydration, sepsis or
treat with metformin (Glucophage or Glucomine).
•
The clinical condition of the diabetic patient may deteriorate rapidly and
response may be suboptimal with more conservative treatment strategies.
COMMON ORGANISMS - UTI
•
•
Commensal organisms in the large bowel , aerobic Gram-negative rods- most
common.
Community or hospital acquired - different pathogenic organism and antibiotic
sensitivity.
–
Community-acquired infections:
•
•
•
–
Nosocomial infections:
•
•
•
E. coli (50%), Pseudomonas aeruginosa, Klebsiela spp., Enterobacter spp., Citrobacter, Serratia
marcescens, Providencia stuartii and S. epidermidis
Often more resistant to frequently prescribed antibiotics.
Less common causative organisms in the presence of a grossly abnormal urinary
tract, immunosuppression or a foreign body.
–
•
Most commonly: Escherichia coli (80%).
Other enterobacteria: Proteus mirabilis and Klebsiela spp.
Gram-positive organisms: Enterococcus faecalis and Staphylococcus saprophyticus.
Fungi such as Candida albicans, Mycoplasma species including Ureaplasma urealyticum,
and viral organisms such as Adenovirus in immunosuppressed bone marrow transplant
recipients.
Urethral infections
–
Chlamydia trachomatis, Neisseria gonorrhoeae, U. urealyticum, and occasionally
Gardnerella vaginalis.
Indwelling urinary catheters & UTI
• Indwelling urinary catheters: the most common source of
nosocomial infections and Gram-negative bacteremia in the
hospital environment.
– Approximately 1—2% risk of infection with a single catheter passage
– Directly related to the duration of catheterization, with the risk of
bacteriuria increasing by
• ~10% per day postinsertion in women
• ~3-4% per day in men.
• Source of this infection –
– via the catheter, the periurethral region, the drainage bag, or connector
disruption with contamination.
• Catheterization < 5 days - bacteriuria from short-term catheterization
usually clears quickly.
• Long-term catheterization –
– Breach in the natural defense mechanisms
– Direct reservoir for bacteria due to adherence to the catheter surface
– Upon removal of a long-term catheter, clearance of bacteriuria may be
improved by administering a short course of antimicrobials.
INTERACTION BETWEEN THE
HOST AND BACTERIA
• To produce a UTI
– Adhere
– Multiply
– Colonize
– Invade the urinary tract
• BACTERIAL FACTORS (FIGURE 8.1)
• HOST DEFENSE (FIGURE 8.2)
Figure 8.1 Bacterial factors that influence the hostbacteria interaction in urinary tract infection (UTI).
Figure 8.2 Local host defense factors that govern host susceptibility in urinary tract infection. HLA, human leukocyte
antigen; PMN, polymorphonuclear; ICAM, intercellular adhesion molecule; IL, interleukin.
Table 8.1 Principles of management of acute severe urinary tract
infections
DIAGNOSTIC MODALITIES- PRINCIPLES
OF MANAGEMENT
• Appropriate treatment of all UTIs requires accurate
categorization of the disease process and exclusion
of all complicating factors.
– infection site
– contributing anatomical variation
– complexity of the infection
– likelihood of recurrence
• Investigations
– REAGENT STRIPS
– URINE CULTURE
– URINARY TRACT IMAGING
REAGENT STRIPS - DIAGNOSTIC
MODALITIES- PRINCIPLES OF MANAGEMENT
•
Nitrite dipstick to
–
–
–
–
•
Leukocyte esterase :
–
–
–
–
•
Detect bacteriuria
Only positive for coagulase-splitting bacteria
Sensitivity : 27-70%
Specificity : 85-94%
Detect pyuria.
Accurate to 10-12 leukocytes/ high-power field (HPF) of centrifuged urine
Sensitivity : 55-85
Specificity : 60-94%
When combined
– False-negative rate :approximately 20%
– Inadequate for the accurate assessment of most UTIs
•
If an accurate midstream urine culture is not obtained
– An opportunity is lost for any subsequent bacterial assessment and tailored
antimicrobial prescribing.
•
Standard reagent strips
– Ideally only be used as screening aids in the initial diagnostic work-up
– Urine culture and antimicrobial sensitivity
URINE CULTURE - DIAGNOSTIC MODALITIES- PRINCIPLES OF MANAGEMENT
•
Gold standard for diagnosing a UTI
–
From an uncontaminated or clean-catch specimen of urine.
•
•
•
•
quantitative bacterial measurement
identify the infective organism
drug sensitivities
Midstream urine : most common technique
–
–
–
Processed within 60 min of collection or refrigerated (4°C) immediately upon collection if processing is to be
delayed.
Length of delay : as short as possible, < 24 hours.
Diagnose a UTI (Table 8.2)
•
•
>100 000 colony-forming units (CFUs) of a single isolate per milliliter of urine.
Up to 30% of women with symptomatic UTIs :
–
–
–
–
Adquate urine collection: examine the centrifuged urine sediment microscopically.
•
•
•
Pyuria (>10 white cells/mm3 of urine)
Minimal introital contamination (<10 epithelial cells/mm3 of urine)
Other techniques : suprapubic aspiration and urethral catheterization.
–
–
•
100 and 10 000 CFUs/ml,
Symptoms are consistent with a UTI ?
A common cause : excessive hydration.
Reduce the risk of contamination
>100 CFU/ml of urine, without evidence of contamination : adequate for diagnosing a UTI in symptomatic
patients.
Sterile pyuria
–
–
Negative urine culture in the presence of pyuria.
DDx :
•
•
•
•
•
•
•
Previously treated UTI
Urolithiasis
Urinary tract tumors
Pregnancy
Foreign bodies such as a ureteric stent
Tuberculosis and other atypical organisms
Spurious causes such as vaginal contamination
Table 8.2 Midstream Urine criteria for urinary tract infections
URINARY TRACT IMAGING - DIAGNOSTIC MODALITIES- PRINCIPLES OF MANAGEMENT
•
Aim (Table 8.3)
–
Diagnose underlying conditions requiring additional treatment
•
•
•
•
•
KUB plus a urinary tract ultrasound scan : sufficient first-line investigation
Intravenous urography (IVU) or computed tomography (CT) imaging : most appropriate
second-line investigations.
–
CT scans
•
•
•
•
•
•
•
Poor renal function or contrast allergies
Evidence of urinary tract obstruction
Antegrade imaging via nephrostomy or retrograde urography
–
•
Superior to renal ultrasonography and IVU
Unenhanced + contrast-enhanced CT: excellent imaging modalities.
Advantages in distinguishing degree and type of involvement of the renal parenchyma
More accurate diagnosis of acute abscesses
Rapid identification of obstructing pathology such as urolithiasis.
Magnetic resonance urography, nuclear medicine renography and retrograde urography
–
–
•
Adequate urinary drainage
Avoid deterioration in renal function and clinical status
Prevent recurrence of infection
Uncommon in the acute setting
In adult female patients diagnosed with an isolated episode of simple acute bacterial
cystitis : imaging, not necessary.
Indications for imaging study:
–
–
Patient's history, such as hematuria and loin pain
Patients with acute pyelonephritis
•
–
Urinary tract ultrasound (in combination with a KUB radiograph) during management - as a screening modality - exclude
any complicating pathology.
UTIs in men
•
•
Ultrasound scans and plain abdominal radiographs
Other investigations
–
–
–
Uroflowmetry
Residual volume estimation
Flexible cystourethroscopy
Table 8.3 Imaging modalities used in the investigation of urinary
tract infections
ANTIBIOTIC THERAPY - PRINCIPLES OF MANAGEMENT
•
•
Table 8.4
Ideal antibiotic
–
–
–
•
Common drugs :
–
•
Tetracyclines and erythromycin.
Trichomonas vaginalis :
–
•
gentamicin, ciprofloxacin, trimethoprim/sulfamethoxazole, amoxicillin and the cephalosporins.
Chlamydiae and mycoplasmas :
–
•
Achieve high renal tissue and urine levels
Bactericidal
Broad spectrum of activity
Metronidazole.
Gentamicin
–
–
–
Most suitable antimicrobial
Bactericidal activity
Combination with β-lactams and vancomycin
•
•
–
•
Added advantage of synergistic activity.
Increase the diffusion of gentamicin across bacterial cell membranes thereby improving efficacy.
Post-antibiotic effect with a large once daily dose producing bacteriostasis several hours after dosage.
Bacterial antibiotic resistance
–
Three mechanisms
1. Natural resistance occurs with the absence of any drug-sensitive strains prior to the initiation of therapy.
2. Resistant mutants - up to 10% , within 48 h of antibiotic treatment.
•
Bacterial transport molecules and molecules aiding the binding of antibiotics to bacterial proteins, eg. 30S ribosomal subunit
binding to gentamicin.
3. Plasmid-mediated resistance (R-factor)
•
–
•
Most important mechanism of bacterial resistance - transfer of multidrug resistance (MDR) genes leading to the production of
'killer' enzymes.
Important to obtain periodic advice from regional clinical microbiologists/infectious diseases physician if
empiric treatment of UTIs is contemplated.
Choice of antimicrobials, adjustments in dosage and length of treatment by coexisting conditions
–
pregnancy, diabetes mellitus, anatomical variation, urolithiasis, neuropathy, renal impairment, hepatic
impairment, immunosuppression and age.
Table 8.4 Aims of management of urinary
tract infections (UTIs)
Table 8.5 Antibiotics used in the management of
urinary tract infections
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT -1
• Gram-negative sepsis (GNS)
– Potentially fatal complication
– Patient whose condition is compromised by underlying medical
and surgical comorbidities.
– Systemic inflammatory response syndrome (SIRS)
– Originates at a local cellular and biochemical level, and manifest
at a systemic (or clinical) level (Table 8.6).
– Gram-negative organisms
• E. coli, Klebsiella spp., Enterobacter spp., Serratia spp.,
Pseudomonas aeruginosa, and Proteus mirabilis
– Lipid-A component of the lipopolysaccharide (endotoxin) in the
Gram-negative cell wall
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT - 2
• Event in GNS
– Localized host reaction to the infectious process,
• i.e. an acute inflammatory response, neutrophil and macrophage infiltration
and initiation of the complement and coagulation cascades.
– Systemic response due to poor control of the local infection, or a
massive bacterial load with the release of bacterial products (cell wall
components /endotoxins) from the pathogens either at localized sites or
within the circulation.
• Bacterial endotoxemia cellular processes in the host release of
endogenous mediators  various biochemical and cellular pathways.
– Tumor necrosis factor (TNF), interleukin (IL)-l, IL-6 and IL-8  further cascading
effects.
– Clinical signs of sepsis, ( fever, tachycardia and hypotension): directly related to
host cytokine levels.
– Complement activation (C3a and C5a)  local tissue damage.
– Other mediators (catecholamines, histamine, kinins, prostaglandins, leukotrienes,
endorphins, and the platelet activating factor)
» Amplify the cytotoxic and inflammatory response
» Producing oxygen free radicals, lysosomal and granular enzyme release,
» Pro-coagulant state with possible disseminated intravascular coagulation
(DIC) with a clotting factor consumption coagulopathy
Table 8.6 Clinical features of Gram-negative sepsis
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT - 3
•
Multiple system failure in GNS (Figure 8.3)
– Circulatory failure
• Multifactorial in origin, with vasodilationrefractory hypotension
– Release of myocardial depressant factor (MDF)
– Endothelial damage
– Microthrombi
– Cardiac failure
• Falling preload
• Hypoperfusion
• Direct myocardial dysfunction from MDF
– Acute renal failure
• Hypoxic acute tubular necrosis
• Microthrombi destroy glomerular filtration secondary to the DIC
• Immune complex deposition further compromising glomerular function.
– Adult respiratory distress syndrome (ARDS)
• Pulmonary toxicity secondary to capillary leak and oxygen free radical injury
– Gastrointestinal tract integrity
• Lost with worsening of the endotoxin insult due to translocation of bacteria
• Endotoxins directly into the circulation
•  Hepatic dysfunction
Figure 8.3 Organ dysfunction in Gram-negative
sepsis.
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT - 4
• Hypercatabolic state due to
hypermetabolism
– Difficult to overcome despite aggressive
nutritional support.
– Ongoing endothelial cell damage produces
worsening DIC
– Blood pressure and urine output fall
– Tachycardia
– Lactate rises
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT - 5
• Management of GNS
– Physiological support
•
•
•
•
•
•
Fluid resuscitation
Oxygen therapy
Ventilatory support
Dialysis
Vasoactive drugs
Metabolic and nutritional therapy
– Antibiotic therapy
• Initially broad spectrum with a β-lactam and aminoglycoside, or
third-generation cephalosporin until positive blood or urine
cultures
– Removal of the source of sepsis
• Emergent basis as necessary
• Drainage of an obstructed renal unit
• Debridement of an infective focus
GRAM-NEGATIVE SEPSIS AND THE PHYSIOLOGICAL
RESPONSE - PRINCIPLES OF MANAGEMENT - 6
• Mortality from GNS
– High in severe cases
– Factors for reducing motality:
• Early diagnosis
• Aggressive therapy
• Appropriate intensive care unit (ICU) referral
– Other measures :
•
•
•
•
•
Antiendotoxin antibodies
Anticytokine antibodies
Monoclonal antibodies targeting leukocyte receptors
Nitric oxide synthase inhibition
Steroid therapy
– To date, despite promising results in animal models of sepsis, no
dramatic clinical benefit in human disease has been shown.