Enteric Bacteria - inflammatory diarrhea Flashcards
What are the bacteria that cause inflammatory diarrhea?
Shigella, EHEC, EIEC, salmonella, c. Jejuni, c. Difficile, yersinia enterocolitica.
Why don’t ecoli cause problems normally even though it’s in GI tract normally?
Don’t cause infection because they lack PAI
General characteristics of shigella, ecoli, and salmonella?
-gram neg facultative anaerobic rods! -ferment glucose with acid production -oxidase negative - reduce nitrates to nitrite (dipstick test) -motile except shigella - antigenic structures used in serotyping -h for flaggelar antigens -o antigens on o side chain of LPS- ecoli part of normal GI tract flora but don’t cause infection because they lack PAI
General characteristics of shigella
- gram negative, non motile, nonlactose fermenting, don’t produce h2s
Most common cause of shigella in us?
S. Sonnei - 70% of cases in US esp in children
Most common cause of shigella worldwide?
S. Flexneri. 2nd most common cause in the US
Most common cause of shigellosis in south and Central America
S. Dysenteriae
Epidemiology of shigellosis
One of the mcc of BLOOdy diarrhea Highly transmissible via fecal oral route…low infectious dose needed DAYCARE centers!!! Migrant workers, travelers to developing countries, nursing homes
Pathogenesis of shigella?
- resistant to acidic environment of stomach- gets taken up by m cells of the intestine –> proliferate intracellularly and move into lamina propria where macrophages phagocytize them causing apoptosis –> inflammation –> damage to epithelial helping shigella gain access to colonic epi cells they can no invade - shigella goes to adjacent cells via bacterium induced membrane bound protrusions from surface of host cell- these protrusions occur via formins which are cellular actin polymerization proteins - bacteria lyse surrounding membrane to go to cytoplasm of new cell
Clinical course of shigellosis
Incubation period is 1 week, Abdominal pain, diarrhea and fever x 1 week Watery diarrhea –> bloody diarrhea in half the cases
Complications of shigellosis
Reactive arthritis, urethritis, conjunctivitis, Hus can occur in some ppl after infection with S. Dysenteriae producing shiga toxin (AB toxin)
Tx of shigellosis
Ab shorten course and duration of shedding of organisms in stoolsCeftriaxone, cipro, azithromycin
General characteristics of enterohemorrhagic e.coli
- called STEC (shiga toxin producing E.coli)
- cant ferment sorbitol like other types of E. coli
- categorized as 0157:h7 or non-0157:h7
- RAW HAMBURGERS, contaminated veg and milk
- can also be transmitted human to hum
- need low infectious dose
Pathogenesis of EHEC
- Locus of Enterocyte Effacement (LEE)
- PAI
- Type 3 secretion system- injectisome
- deliver Ecoli R to host cell
- pedestal formation for attachment
- responsible for diarrhea
- Shiga toxins - AB toxin
- b subunit bind toxin to its receptor on cells
- A subunit then enters the cytosol and cleaves a specific adenine residue from the 28S rRNA of teh 60S ribosomal subunit –> stop protein synthesis –> cell death
Clinical presentation
- little fever, acute onset of cramps and watery diarrhea
- watery diarrhea –> bloody diarrhea (hemorrhagic colitis) within 24 hours. can last about 8 days.
- O157:H7 strains–large outbreaks, bloody diarrhea, HUS, and ischemic colitis
What do shiga toxins do?
remove adenine from large (28S ribosomal RNA) –> stopping protein synthesis.
What is one of the main casues of AKI in children under 3?
HUS- hemolytic uremic syndrome
Which bacteria has complications causing HUS?
EHEC (>90% in children) and Shigellosis (less common)
clinical manifestations of HUS
- 5 days after onset of diarrhea
- microangiopathic hemolytic anemia and thrombocytopenia
- AKI w/ dialysis required in > 50% of pts (most regain kidney function)
- neurologic symptoms like seizures and somnolence in 25%
mortality rate about 5%
How do shiga toxin cause damage?
absorbed in inflamed GI mucosa into circulation where it alters endothelial cell function –> platelet activation and aggregation somehow.
** hemolytic anemia and renal failure occur bc there are Rs for shiga toxin on surface of endothelium of small blood vessels and on the surface of kidney epithelium.
- death of endothelial cells of small blood vessels result in microangiopathic hemolytic anemia –> schistocytes and then lysis or RBC.
- Thrombocytopenia occur bc platelets adhere to the damaged endothelial surface . Death of kidney epithelial cells lead to renal failure.
how do you diagnose EHEC
- use sorbitol macconkey agar- the 0157:h7 strain doesnt ferment sorbitol so will be white but other ecoli and EHEC will be red/pink
- PCR or ELISA to detect Shiga toxin
Tx for EHEC?
- supportive care and monitoring for complications
- Avoid anti-diarrheals as they can risk systemic complications
- Antibiotics not helpful and may predispose HUS by inducing more shiga toxin release!
General characteristics of EIEC (enteroinvasive E. Coli)
- similar to shigella and causes similar disease but no toxins produced
**- **food/water transmission
- person to person contact
- most commonly seen in YOUNG CHILDREN IN DEVELOPING COUNTRIES.
pathogenesis of EIEC
- bacteria invades intestinal cell–> multiplies intracellularly and extends into adjacent intestinal cells
General characteristics of Salmonella
gram negative bacilli
- non lactose fermenting
produces H2S
- Salmonella Enterica- typhoid fever. does NOT cause gastroenteritis
- S. Paratyphi-like typhoid fever also and does NOT cause gastroenteritis
- Nontyphoid salmonella aka S. enteritidis- DOES cause gastroenteritis from food poisoning.
Salmonella enteritidis source of infection?
- dairy products, meat, poultry and eggs
- pet turtles, lizards and other reptiles
- human to human
pathogensis of salmonellosis
- attach to M cells and endocytosed through complex pathway
- type 3 syringe secretion system capable of tranferring bacterial proteins into M cells and enterocytes
- bacterial proteins trigger endocytosis and allow bacterial growth within endosomes
- bacteria cross basal membrane to enter the lamina propria
- inflammatory response occurs: s. enteritidis also kills macrophages
clinical presentation of salmonellosis
- incubation period 1-3 days
- Nausea, vomiting, diarrhea (can be bloody), crampy abd pain
- fever in 50%
illness lasts about 3-4 days
- 5% will develop invasive disease like bacteremia, endovascular infections, endocarditis, osteomyelitis
- predilection for aortic plaques, and bone prosthesis.
- can also develop reactive arthritis
how do you diagnose salmonellosis?
routine stool culture
Tx of salmonellosis?
- not required for healthy ppl btwn ages of 2 and 50
- tx indiciated for those at risk of disseminated/invasive disease:
- like immunicompetent patients with severe infection requiring hospitaliztion,
- suspected atherosclerotic plaques and endovasuclar/bone prostheses
- immunocompromised ppl like HIV, those receiving steroids, sickle cell disease
- Tx : Flouroquinolones- susceptibility testing should be performed
general characteristics of typhoid fever
- caused by s enterica. s. paratyphi can cause a similar illness
- humans are sole reservoir
- transmission person to person (fecal-oral, infected food handler) or via contaminated food/water
children and young adults > older pts
- worldwide, impoverished, overcrowded area with poor access to sanitation
- travelers to south central asia
outbreaks in US most often foodborne
pathogenesis of typhoid fever
- in small intestine, organisms are taken up by and invade M cells
- bacteria engulved by macrophages in the lyphoid tissue
- organisms disseminate to lymph nodes and RES –> spread to blood (sepsis)
- organism can proliferate in submucosa leading to hypertrophy of peyer’s patch d/t influx of inflammatory cells
- chronic carriage can occur in biliary tract
- hypertrophy and subsequent necrosis of submucosal tissue can cause GI tract perforation.
clinical presentation of typhoid fever
- incubation period 5-21 days
- 1st week of illness: rising fever/ chills develop. pts are bacteremic. relative brady can be observed
- 2nd week: abd pain and rose spots on turnk/abd
- 3rd week: hepatosplenomegaly, GI bleed, perforation, secondary bacteremia (septic shock and AMS can occur)
- in absence of death or severe complications, symptoms resolve over weeks to months
Diagnosis of typhoid fever
- blood cultures positive in 50-80% of pts. May require several days of incubation
Tx of typhoid fever
- Ceftriaxone, azithro, cipro (unless pt has been in an area with high rates of flouroquinolone resistance such as south asia)
**prevention with vaccine
general characteristics of Campylobacter jejuni?
thin, spiral shaped gram neg rods (C.coli) is another species that can cause enterocolitis
- most common bacterial enteric pathogen in developed countries
- important bc of TRAVELER’S DIARRHEA
- most infections d/t eating improperly cooked chicken, unpasterized milk or contaminated water
- low infectious dose needed
reservoirs: sheep, cattle, chicken, dog, wild birds
clinical presentation of c. jejuni
- incubation period 1 week
- watery diarrhea (10+ bm/day) –> bloody diarrhea in 15% of adults and > 50% of children
fever, crampy periumbilical abd pain
- self limited over 3-7 days
diagnosis of C. jejuni?
stool culture
Tx of C. Jejuni?
- Only warranted for those with severe disease or at risk of severe disease (bloody stools, high fever, worsening symptoms)
- azithromycin, cipro are DOC, resistance to fluoroquinolores are rising though
Complications of C. Jejuni?
Guillain barre syndrome- develops in only 0.1% or less
- molecular mimicry implicated in pathogenesis: serum ab to c. jejuni LPS cross-react with peripheral and central nervous system gangliosides
- erethyma nodosum
- reactive arthritis- more commonw ith HLAB27 phenotype—can also be seen with salmonella shigella and yersinia
reactive arthritis can be a complication of disease caused by which bacteria?
- salmonella, shigella, and yersinia
general characterisitics of yersinia enterocolitica
- gram - coccobacilli with bipolar staining
- more common in eurpoe
- sources: pork, raw milk, contaminated water, pet feces
- infection prefers ileum, appendix, and right colon (organisms multiply in lymphoid tissue resulting in regional lymph node and peyer patch hyperplasia)
clinical presentation of yersinia enterocolitica?
- abd pain- main feature (peyer patch and mesenteric lymph node hyperplasia can mimic appendicitis in teens and young adults)
- nausea/vom
- fever/diarrhea
- extraintestinal symptoms like pharyngitis, arthralgia, erythema nodusm
diagnosis of yersinia enterocolitica?
stool culture
tx of yersinia enterocolitica
most cases dont warrant tx
general characteristics about C. diff
anaerobic, spore forming gram positive rod
- fecal oral transmission
- hands of hospital personal
- most common NOSOCOMIAL CUASE OF DIARRHEA and MOST COMMON cause of antibiotic associated diarrhea
pathogenesis of c diff?
- ab suppress normal flora allowing c diff to multiply and produce exotoxins A and B
- Exotoxins A and B cause glucosylation of small GTPases such as Rho which are involved in cytoskeleton structure and signal transduction
- toxin A (enterotoxin) - disrupt colonic mucosal cell adherence to colonic basement membrane and damage villous tips. inflammation –> fluid secretion
- toxin B (cytotoxin)- cause depolymerization of actin causing loss of cytoskeletal integrity –> apoptosis and death of enterocytes
- both toxins (A > B) stimulate monocytes and macrophages, which release IL8 resulting in tissue infiltration with neutrophils; both cause disruption of epithelial tight junction
Clinical presentation of C diff?
- watery diarrhea!
- cdiff associated diarrhea with colitis (CDAD)- watery diarrhea (10-15 bm/day), mild lower abd pain/cramping, low grade fever, leukocytosis
** CDAD occur in setting o ab. Symps begin during ab therapy or 5-10 days following ab administration
- pseudomembranous colitis- similar presentaiton but in sigmoidoscopy it shows pseudomembranes (Adherent layer of inflammatory cells and debris at sites of colonic muscle injury)
- Fulminant colitis- severe disease (severe abd pain, abd distention, fever, hypovolemia)
- toxic megaoclon: colonic dilatation > 7cm with severe systemic toxicity
- hypervirulent strains are emerging with more severe disease, lower clinical cure rates and high relapse rate.
Risk factors for C diff infection?
advanced age, hospitalization, antibiotic tx
diagnosis of c DIFF?
- PCR detect toxins A and B
- EIA for tonxis A B but there’shigh false negative rate
- cell culture cytotoxicity assay- gold standard. stool sample added to monolayer of cultured cells. if c diff toxin present, it exerts cytopathic effect in tissue culture. labor intensive.
c diff tx?
- flagyl 1st line. if severe, PO vanc as first line
- 1st recurrence: flagyl,
2nd recurrence: vanc extended course
- fidaxomycin- new. superior clinical response and less recurrences when compared with vanc
- fecal transplants
