Download Urogenital Infections

Microbiology: Urinary Tract Infections (Withey)
DEFINITION OF UTI BY LOCATION:
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Kidney: pyelonephriis
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Ureter: ureteritis
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Bladder: cystitis
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Prostate: prostatitis
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Urethra: urethritis
UTI DEFINITIONS AND CLINICAL PRESENTATION:
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Lower UTI: cystitis, prostatitis, urethritis
Cystitis: dysuria, urinary urgency and frequency, bladder fullness/discomfort; may also have hematuria
Prostatitis: pain in lower back, perirectal area and testicles (as well as the above symptoms)
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Upper UTI: pyelonephritis, intra-renal abscess, perinepheric abscess (late complication of pyelonephritis)
Pyelonephritis: cystitis symptoms as well as the following
o
Fever/sweating
o N/V/D
o Flank pain
o Signs/symptoms of dehydration or hypotension
o Can show signs of speticemic shock
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Uncomplicated UTI: infection in a structurally and neurologically normal urinary tract
Little to no effect on long term renal function
Simple cystitis of short duration that is easily cleared with antibiotics
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Complicated UTI: infection in a urinary tract with functional or structural abnormalities (indwelling catheters, renal
stones, enlarged prostate)
Causes cystitis of long duration or hemorrhagic cystitis
UTIs in males always considered complicated
Antibiotic resistant bacteria also fall into this category
ETIOLOGY OF UTIs:
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E.coli is the leading cause of both complicated and uncomplicated UTIs
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Uncomplicated: E.coli, S.saprophyticus
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Complicated: E.coli, Enterococcus, P.aeruginosa, Klebsiella, Proteus (an many others)
GENERAL PATHOGENESIS:
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Entry: ascent from urethra (how far it ascends depends on virulence factors)
Often due to poor hygiene (inoculation from host flora) or sexual contact
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Adherence to host epithelium: most important factor in pathogenesis
Negative charge on both bacteria and epithelial surfaces, and therefore, the bacteria need organelles to reach
out and attach host cells, effectively overcoming repulsive forces
o 10um is the maximum repulsion zone
o 15um is where they want to be
Examples: adhesions, pili/fimbriae (Gram negatives) and polysaccharides (G positives)
ORGANISMS CAUSING UTIs:
Uropathogenic E.coli (UPEC):
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Virulence Factors:
Pili/Fimbriae-Associated Adhesins:
o P Pili Associated with Pyelonephritis (PAP):
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Binds to digalatoside receptor (glycopshingolipid/globobiose)
 Individuals can be predisposed to infection due to high density of these receptors
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Mannose insensitive (binding not blocked by mannose)
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Causes hemagglutination in lab (binds P Ags on RBCs)
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Help resist phagocytosis
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Proflammatory (induce IL-6, IL-8 and PMN infiltration)
o Type 1 Pili:
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Binds to mannose (therefore mannose sensitive) in order to mediate binding to
uroepithelium
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Agglutinates RBCs
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Invertible promoter element that allows it to be turned on in the bladder and off in the
kidney
o Type S Fimbriae (SfaI and SfaII):
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Binds to sialic acids on glycoproteins (therefore, mannose insensitive)
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Agglutinates RBCs
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Causes both cystitis and pyelonephritis
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Often associated with neonatal meningitis and bacteremia
Afrimbrial Adhesins:
o Recognize Dr blood group Ags
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AfaD and AfaE aid in adhesion to uroepithelium and internalization (recurrent UTIs)
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Dr adhesion recognizes basolateral surface integrins to aid in internalization (recurrent UTIs)
Toxins:
o Alpha hemolysin:
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Lyses RBCs (iron for growth) and renal tubular cells
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Mediates kidney damage in pyelonephritis
o Cytotoxic necrotizing factor type 1 (CNF-1):
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Kills human bladder epithelium by apoptosis
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Mutants in CNF-1 are not as virulent
LPS (Endotoxin):
o Proinflammatory cytokine release
o Synergistic effect with P fimbrae
K Antigen (Polysaccharide Capsule):
o Anti-phagocytic/serum resistance
Etiology/Pathogenesis:
Causes 80-90% of CA-UTIs: more common in females than males
Source: host’s own intestinal flora or sexual partner’s flora
Ascending Infection of Urethra:
o E.coli bind to urethra using Type 1 fimbriae (not washed out)
o Ascend further to bladder where they again bind using Type 1 fimbriae with FimH tip
o Move up ureter using flagellar motility
o Reach the kidney where P fimbriae with PagG tip mediate binding (antigen switch to evade immune
response as well)
Inflammatory response and toxins contribute to cell damage
Laboratory Identification:
Examination of Urine:
o Gram stain: look for Gram negative rods, RBC and WBC
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Note: Gram + rods adhering to epithelial cells are lactobacilli (normal flora)
o Blood agar plate: beta hemolysis and quantitation
o Selective Media:
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MacConkey: lactose positive colonies (red/pink)
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Cysteine-lactose-electrolyte deficient agar (CLED): yellow colones
o Indole Test: pink/purple
o Oxidase test: negative
Need to differentiate between infection and contamination:
o BAP: streaked with calibrated loop so that 1 colony= 100 CFU/ml
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Contaminants/Normal Flora: less than 10,000 organisms per mL
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Questionable/Repeat: 10,000-100,000 organisms per mL
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Bacterial Infection: greater than 100,000 organisms per mL
Staphylococcus saprophyticus:
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Virulence Factors:
S.saprophyticus surface associated protein
Hemagglutinin/fibronectin-binding protein
Hemolysin: not in all uropathogenic strains)
Urease: hydrolyzes urea to give ammonium ions
o Toxic to bladder tissue
o Raises pH of urine (promotes formation of kidney stones that can obstruct urinary tract)
o Struvite stones with chronic UTIs (magnesium ammonium phosphate)
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Etiology/Pathogenesis:
Causes: urethritis and cystitis (rarely associated with pyelonephritis)
More common in females
Possible Risk Factors:
o Auto-infection (colon)
o Sexual activity
o Hormone flux at menstruation
o Spermicide nonoxynol-9
Laboratory Identification:
Shape: Gram positive cocci in clusters
Growth: CNA agar (none of MAC, EMB or CLED)
Biochemical: catalase positive, coagulase negative, novobiacin resistant
Klebsiella pneumoniae:
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Virulence Factors:
Type 1 Fimbriae: mannose sensitive hemagglutinin
Type 3 Fimbriae: mannose-resistant hemagglutinin
Polysaccharide Capsule: bilayered and anti-phagocytic
LPS: serum resistance (mediated by O antigen)
Urease: hydrolyzes urea to give ammonium ions (stone formation; almost 100% produce)
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Etiology/Pathogenesis:
Site of colonization: colon
Infection: most often seen in patients with underlying disease (ie. diabetes)
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Laboratory Identification:
Shape: Gram negative rod
Appearance: mucoid colonies (due to capsule)
Growth: lactose positive on MAC, EMB and CLED; non-hemolytic on BAP
Proteus mirabilis:
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Virulence Factors:
Adhesins:
o MR/P (Mannose Resistant Proteus-like):
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Hemagglutinin
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Contributes to colonization of urinary tract
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Increases risk of acute pyelonephritis
o PMF (Proteus miribalis fimbria):
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Not a hemagglutinin
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Contributes to colonization of the bladder (not the kidney)
Flagella: highly motile (swarming motility; contributes to ascending infection from ureters to kidney)
Urease: STRONG producer of urease (rapidly causes stone formation)
HpmA Hemolysin: potent and cytotoxic for a variety of cells
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Etiology/Pathogenesis:
Site of colonization: colon
Infection: most often seen in patients with underlying disease
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Laboratory Identification:
Shape: Gram negative rods
Growth: lactose negative on MAC, EMB and CLED; hemolytic with swarming phenomenon on BAP
Smell: highly urease positive and culture reeks of ammonia
Enterococcus spp:
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Virulence Factors:
Aggregation Substance (Asa1)
o Facilitates conjugal plasmid exchange between cells
o Adhesion to eukaryotic cells expressing integrins
Cytolysin: lyses RBCs (iron for growth)
Sex Pheromones:
o Normally function in plasmid acquisition
o Triggers immune response as neutrophil chemoattractant
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Etiology/Pathogenesis:
Site of colonization: colon
Infection: more often seen in hospitalized patients with indwelling catheters
Laboratory Identification:
Shape: Gram positive cocci
Growth: salt tolerant (will grown in 6.5% NaCl)
Biochemical: bile esculin positive; catalase negative
HOST PROTECTIVE MECHANISMS:
Normal flora: but urinary tract is normally sterile (only in the anterior urethra)
Flushing action of urine
Sloughing of the pithelium
High osmolality, low pH: hard for bacteria to survive
Insignificant immune defense
HOST FACTORS IN INFECTION:
Uroepithelial receptors that bacteria recognize (mannose R)
Women with recurrent UTIs tend to have more mannose receptors
Pk and P1 blood groups more prone to developing recurrent UTIs
Blockage or other physiological malfunction (neurological disorder, pregnancy, diabetes etc.) in urinary tract
allows bacteria to migrate against the flow of urine