47. E.coli & Enterobacteriaceae Flashcards
1
Q
E coli general characteristics?
A
- facultative anaerobe (the most common)
- mostly harmless commensals
- beneficial metabolites
- colonization resistance contribution
- resistant to PCN
- increasing resistance to other Abx re: plasmids
- sensitive to cephalosporis, monobactams, carbapenems, TMP-SMX, FQ, gentamicin
2
Q
enterobactericeae general characteristics?
A
- GN anaerobic bacteria
- ferment sugars
- motile w/flagella
- colonize lower GI tract
- survive in water
- O serotype: repeating carb side chain of LPS
- H serotype: flagellar antigen (variability in flagellin)
3
Q
ETEC epidemiology? clinical picture?
A
- dehydrating diarrhea in developing world (kids*)
- traveler’s diarrhea
- watery diarrhea (mild in adults can be as bad as cholera in kids)
- N/V, malaise, anorexia, Abd cramping in 25%
- dehydration in 20%
- short duration
4
Q
ETEC pathogenesis?
A
- Fecal-oral route, high inoculum to cause disease
- colonization factor antigens (CFA): fimbria involved in adherence; important for immunity, req for virulence
- heat-labile enterotoxins: 1A and 5B subunits, B binds GM1, enters cell via retrograde transport, A1 fragment causes ADP ribosylation of G protein locking it “on”, activates AC, increased cAMP, activates PKA, phosphorylates and opens CFTR, chloride secretion
- heat-stable enterotoxins: small peptides, related to guanylin, binds transmembrane guanylate cyclase receptor, causes increase cGMP
5
Q
ETEC dx and treatment/prophylaxis?
A
- referral labs
- Avoidance: only bottled beverages (no ice), cook food HOT
- oral rehydration
- Abx can shorten course of traveler’s diarrhea: FQ w/or w/out loperamide (anti-motility agent) OR rifamixin
6
Q
EPEC epidemiology and clinical picture?
A
- impt in infants in developing countries worldwide
- potentially deadly
- “atypical” strains in childhood diarrhea in developed countries (no bundle-forming pillus)
- watery diarrhea, w/fever and vomiting
- severe and protracted
- may lead to malabsorption
**mechanism of diarrhea still unclear
7
Q
EPEC (enteropathogenic E.coli) pathogenesis?
A
- initial “localized adherence” to cells by plasma-encoded bundle-forming pilus (typical strains only): causes bacteria to aggregate in microcolonies, adhesion w/host cell carbohydrate receptor, required for virulence
- encoded on locus of enterocyte effacement (LEE) pathogenicity island: necessary and sufficient for attaching and effacing, type III secretion system injects effector proteins into host cells, Tir (translocated intimin receptor) encoded by tir gene inserted into host cell membrane by this T3SS, intimin encoded by eae gene is an outer membrane protein adhesion, required for virulence in volunteers -> intimin binds Tir and activates cellular actin machinery.
- T3SS also injects several proteins that block tight junctions and NFkB signaling and thus innate immune response
8
Q
EPEC diagnosis and treatment/prophylaxis?
A
- referral labs for dx
- PO, if needed IV, rehydration
- supportive care
- Abx possibly effective BUT high levels of resistance
- breast feeding is higly protective
9
Q
EHEC (enterohemorrhagic E.coli) epidemiology and clinical picture?
A
- hemorrhagic colitis due to serotype O157:H7 assoc w/hamburgers
- many outbreaks and sporadic cases
- highest incidence in kids under 5, summer
- transmission: food (ground beef), swimming/drinking water, person-person (household), petting zoos
- low inoculum
- severe cramps, abd pain and watery diarrhea
- gross blood (30-65%)
- little or no fever
- HUS/TTP: 4% of cases, esp kids and elderly; microangiopathic hemolytic anemia, thrombocytopenia, kidney failure; ischemic infarcts of bowel, brain, heart; 12% die or have ESRD, 25% survive w/kidney damage
10
Q
EHEC pathogenesis?
A
- O157:H7 evolved from atypical EPEC
- LEE, attaching and effacing activity similar to EPEC
- STEC (non-O157:H7 that produce shiga toxin but lack LEE)
- Shiga toxins acquired via bacteriophage: 1A 5B subunits, B subunit binds GB3, A subunit depurinates 28S rRNA leading to cessation of protein synthesis and cell death
- induced by SOS response (antibiotics or oxidative stress) that leads to phage production and cell lysis
- thought to enter circulation, damage endothelial cells leading to platelet activation, thrombin deposition, and organ failure
11
Q
EHEC dx and tx?
A
- Sorbitol MacConkey agar (O157:H7 can’t ferment sorbitol and stay white, most E.coli turn it pink re: fermentation)
- ELISA for shiga toxins
- test all pts w/bloody diarrhea
- test all pts w/HUS, TTP, or variants
- supportive care
- avoid antimotility agents
- use of Abx assoc w/greater production of Shiga toxin and higher risk of HUS
- avoid cross-contamination
- cook ground beef until juices are clear
- avoid unpasteurized milk/juice
12
Q
EAEC? enteroaggregative E.coli?
A
- assoc w/childhood diarrhea in developing countries (can be persistent)
- traveler’s diarrhea
- emerging pathogen in developed countries causing outbreaks
- diarrhea in HIV pts
- watery diarrhea w/mucous +/- blood
- intestinal “colic”
- growth retardation
- aggregative adherence: plasmid encoded-fimbriae, >2 different fimbriae mediate same phenotype
- damage to intestinal cells
- toxins (plasma encoded and some heat-stable)
referral labs for dx and we don’t yet know therapy tx!
13
Q
extraintestinal E.coli infections?
A
- 2nd most common cause of meningitis in infants
- common cause of UTIs
- frequent pathogen in cholecystitis and peritonitis
14
Q
extraintestinal E.coli pathogenesis?
A
- acquired during birth from mom, pathogenesis via K1 capsule (homopolymer of sialic acid) like GBS capsule, necessary but not sufficient for disease; masks activation of alternative C’ pathway
- more able to invade endothelial cells than most E.coli
- some genes involved encoded on pathogenicity islands
treat w/3rd generation cephalosporin
15
Q
klebsiella?
A
- UTI
- severe pna
- nosocomial infections
- highly mucoid colonies due to capsule
treatment:
- always resistant to pcns
- some strains multi-resistant
- usu sensitive to cephalosporins
16
Q
enterobacter?
A
- nosocomial infections
- encapsulated, mucoid
- chromosomal cephalosporinase is highly inducible
- some strains are multi-resistant
17
Q
proteus disease?
A
- UTIs, esp w/ catheters and urinary tract abnormalities
- S/ST infections like skin ulcers in pts w/ diabetes
18
Q
proteus pathogenesis?
A
- highly motile, swarming
- produce urease (catalyzes hydrolysis of urea to make basic pH) causes stone formation, which augments colonization and renders eradication difficult
- fimbriae (related to P fimbriae) essential for colonization
- motility – aids in ascending to and colonizing the kidney
19
Q
proteus treatment?
A
- usually sensitive to ampicillin, 1st generation cephalosporins, TMP/SMX
- resistant to tigecycline and polymixin B (unusual for GN bacilli)
