Enterobacteriaceae I & II Flashcards
What are the four UNVARYING characteristics of the family Enterobacteriaceae?
- Facultative G NEGATIVE rods
- ferment GLUCOSE
- Oxidase NEGATIVE
- Reduce nitrate to nitrite
( Indigenous flora of GI tract, colonize respiratory tract of hospitalized pts
–grow rapidly areobically/anerobically (simple growth requirements)
Structure of Enterobacteriaceae
A. LPS (endotoxin)
-3 components:
a. O-antigen: produces distinct serotypes
b. core oligosaccharide: attaches directly to
c. Lipid A: endotoxin component, released into circulation when bacteria cells are lysed; cause fever, diarrhea, and possible fatal endotoxic/septic shock (with AB will get WORSE before you get better)
B. H-antigen: peritrichous (all around) flagella
C. K or Vi-antigen: more than 80 serotypes in capsule (important in causing extraintestinal colonization, UTI, and invasive disease–prevents phagocytosis)
7 Enterobacteriaceae Virulence Factors
- Endotoxins
- Capsule: protects from phagocytosis
- Antigenic Phase variation: protects from antibody mediated cell death
- Type III secretion systems: facilitates secretion of bacterial virulence factors into host cells
- Sequestration of growth factors-eg. Iron scavengers
- resistance to serum killing
- Antimicrobial resistance
What is a MacConkey agar?
Selects for gram NEGATIVE has bile salts inhibitory to gram POSITIVE and crystal violet which also inhibits G+.
- Non-lactose fermenters –> colorless
- Lactose fermenter –> purple
List the 7 established genera/tribes
- Escherichieae
- Edwardsielleae
- Salmonelleae
- Citrobactereae
- Klebsielleae
- Proteeae
- Yersinieae
Tribe 1. Escherichieae
5 species, important champ: **E. coli
Habitat: intestines of humans/animals (usually self inflicted, gets into a place it doesnt belong)
E. coli Habitat
- what does its presence indicate?
- when do babies acquire it?
- Its a free living organism, right?
- in humans, infants acquire within hours of birth
- its presence in water=indicator of fecal contamination
- NOT considered as a free living organism in the environment
E coli Clinical Syndromes
- gram NEGATIVE sepsis
- UTI (80% of community acquired UTIs)
- wound infections
- pneumonia in IC hospitalized pts
- Meningitis in neonates
- Gastroenteritis
What are the strains of E. coli that cause gastroenteritis?
- Enterotoxigenic (ETEC)
- Enteropathogenic (EPEC)
- Enteroinvasive (EIEC)
- Enterohemorrhagic (EHEC)/Shiga toxin producing (STEC)
- Enteroaggreative (EAggEC)
Pathogenic Phenotype of ETEC
elaboration of secretory toxins (LT, ST) that do not damage the mucosal epithelium
Signs and Symptoms of ETEC
- secretory diarrhea (traveler’s diarrhea) similar to V. cholerae (go to Mexico and drink the water)
- ***profuse watery diarrhea is predominant symptom
- often accompanied by mild abdominal cramps
- dehydration and vomiting occur in some cases
Pathogenic Phenotype of EPEC
adhere to epithelial cells in localized micro-colonies and cause attaching and effacing lesions
Signs and Symptoms of EPEC
- usually occurs in INFANTS
- characterized by low-grade fever, malaise, vomiting, and diarrhea
- prominent amount of mucus but with NO GROSS BLOOD
Pathogenic Phenotype of EIEC
invade epithelial cells and elicits immune resp
Signs and Symptoms of EIEC
- inflammatory diarrhea (dysentery) similar to shigella
- hallmarks: fever and colitis
- symptoms: urgency and tenesmus (a continual or recurrent inclination to evacuate the bowels)
- BLOOD, MUCUS, and MANY LEUKOCYTES in stool
Pathogenic Phenotype of EHEC/STEC
- elaboration of cytotoxins (Shiga toxins, Stx1 and Stx2)
- primarily caused by E. coli O157:H7 (serotype)
Signs and Symptoms of EHEC/STEC
- BLOODY DIARRHEA sans wbcs
- often no fever
- abdominal pain is common
- may progress to hemolytic uremic syndrome (HUS)
Pathogenic Phenotype of EAggEC
adhere to epithelial cells in a pattern resembling a pile of stacked bricks
Signs and Symptoms of EAggEC
symptoms include:
- WATERY DIARRHEA WITH BLOOD AND MUCUS
- vomiting
- dehydration
- less commonly: abdominal pain
STEC-Shiga Toxin Producing E. Coli
- produce 1 or more Shiga toxins (verocytotoxins)
- produce attaching and effacing lesions
- E coli O157 most commonly identified serotype
- incidence and major serotypes of non-O157 strains causing diarrhea and HUS not determined
E. coli O157 Transmission
- STEC is shed in feces of cattle, sheep, deer, other ruminants
- human infection acquired via contaminated food/water OR via direct contact with an infected patient
E. coli O157 illness and modes of transmission
- foodborne outbreaks most commonly associated with undercooked ground beef
- reservoir: healthy dairy cattle
- sporadic cases assoc. with unpasteurized milk, apple cider, lettuce and other produce, petting zoos, state fair show barns, contaminated water
- largest US outbreak occurred in w. USA (‘93). Over 500 confirmed cases, 41 with HUS, 4 deaths. Jack-in-the-Box undercooked hamburgers.
- causes both bloody and non-bloody diarrhea
- ***HEMOLYTIC UREMIC SYNDROME (HUS), HEMORRHAGIC COLITIS
- young children and elderly at increased risk for severe complications
STEC Incidence
- an estimated 265,000 STEC infections occur/yr in the US
- STEC O157=36% of these infections + 60 deaths/yr
What are the physical manifestations of E. coli O157 HEMORRHAGIC COLITIS
- abdominal cramps, watery diarrhea, bloody discharge
- no significant fever
- absence of WBC in stool
What are the physical manifestations of E. coli O157 HUS (hemolytic uremic syndrome)
- HAT triad of symptoms for HUS:
1. hemolytic anemia
2. acute renal failure
3. thrombocytopenia (no platelets) - preceded by bloody diarrhea
- leading cause of acute renal failure in children
- occurs in 20% of pediatric O157:H7 cases
- 50% require dialysis, 3-5% die
- usually diagnosed a wk after diarrhea onset
EHEC (Enterohemorrhagic)-Clinical symptoms
-3-4 days non-bloody diarrhea with abdominal pain
-onset of bloody diarrhea and severe abdominal pain
-resolution in 4-10 days
OR
-HUS–> death or sequelae (renal impairment [not urinating], HTN, or CNS dysfunction)
E. coli O157:H7 histology
- schistocytes=fragmented RBC–> microangipathic
- hemolytic anemia–>lethargy
- hyperchromic cells (white centers)
- white cell surrounded by red cells, but no platelets (thrombocytopenia)
- already in reanl faillure, not urinating–>One of the HUS-HAT triad
Actions of the toxins (1/2)
- organism never invade bloodstream, produce shiga toxins which invade, attach to receptors on endothelial cells in blood vessel lining (largest [ ] of receptors for shigatoxin are in the renal epithelial area-around the kidneys)
- toxin adherence–>damage to vessel wall
- body response by forming a scab+consuming plateley
- small narrow vessle with fibrin deposits on inside of vessel wall narrow lumen, RBC stat shearing on rough surface
- oxygen supply to kidney starts to get affected, pt goes into renal failure
- infarction of mucosa–>bleeding into bowel and bloody diarrhea
- inhibition of protein synthesis targets:
1. commensal bacteria
2. host cells
Action of the toxins (2/2)
- toxins also trigger many signaling cascade influencing cellular functions such as cytokine secretion and the induction of cell death by apoptosis
- many endothelial and epithelial cells in the kidney and the CNS are sensitive to cytotoxicity induced by Shiga toxins
E. coli O157:H7 Complications of HUS
- 3-5% die acutely
- 14% develop sever in-hospital complications i.e. stroke, blindness, bowel resection
- 39% develop chronic kidney abnormalities years later
What are the two settings in which E. coli O157:H7 can occur?
a. diarrheal related-classical HUS, vast majority of cases
b. non-diarrheal HUS-much less common can occur in association with:
- pneumococcal infection
- chemotherapy
- transplant immunosuppression
What are risk factors for HUS following O157 infection?
- Host factors
- very young or old
- mental retardation
- P antigen expression by RBCs (carried by 50%, also on other tissue including endothelial cells, attachment site for Shiga) - Clinical Factors
- bloody diarrhea
- fever
- increase WBCs - Treatment Factors
- use of anti-motility agents
- use of certain antimicrobials - Other factors
- produce STII instead o both I and II
Emergence of EHEC/STEC NON-O157 disease
- more than 150 serotypes identified
- most freq in N. America: O26, 45, 103, 111, 121
Laboratory Diagnosis-collection and transport of specimens
- Timing: collect in early stages of any enteric illness (first 4 days of onset) when organism load is higher and before antibiotic tx is initiated
- Type: whole stool, multiple specimens
- Transport: ASAP, refrigerate at 4C if >1-2hrs
What are the three main modalities to detect antigen?
- direct fecal specimen detection
- enriched broth culture detection (more sensitive)
- FilmArray GI panel-multiplex PCR
How is STEC Diarrhea treated?
(treat symptoms)
- oral rehydration (Gatorade, Pedialyte), supportive care and careful monitoring of kidney function
- HUS and renal failure: can be managed by dialysis
- ***Antibiotics are NOT given in STEC!!! (it would kill all the E coli, release all the shigatoxin and endotoxin at once, endo would enter bloodstream and upregulate shiga activity)
- ***No antimotility agents!!!
- ***Chemoprophylaxis with SXT or ciprofloxacin for travelers’ diarrhea NOT recommended
Tribe I: Escherichieae
- Genus Shigella-4 species: Shigella (dysenteriae, flexneri, boydii, sonnei)
- key ID: MacConkey is flat-dry, NON-lactose fermenter, indoel NEGATIVE, NOT motile, no CO2 (unlike E. coli)
- Habitat: human intestines (20-30k cases/yr in US)
How is Shigella Transmitted? 5Fs + what kind of kids?
- person to person via fecal route
- contaminated water +5 F’s (food, flies, fingers, fomites, feces)
- highest risk: young children in day care center, nurseries, custodial institutions
- siblings and parents of ^ kids
- MSM (fecal oral sans vector)
What is the pathogenesis of Shigella?
- virulent strains carry plasmid for attachment and entry
- enters cells by phagocytic vacuole
- organism escapes in cytoplasm
- intracellular replication
- actin “tail” drives organism in cytoplasm
- organism enter adjacent cells
- Shigella phagocytosed into new cell and released into cytoplasm
- shigella can kill phagocytic macrophages
- infection does not extend into lamina propria
- some strains prodcue shiga toxin–>more severe disease
What are the clinical syndromes of Shigella?
**Bacillary dysentery
-abdominal cramps, tenesmus (urge to stool), pus and blood in stool
-tissue invasion limited to epithelial cells and submucosa
-fecal leukocytes present
-incubation 1-3 days lasting 48hrs
-humans=natural host
-most communicable of bacterial diarrheas
-
Tribe II: EdwardsiellEAE
-*Edwardseilla tarda
Habitat: cold blooded vertebrates (snakes), fresh water, catfish
What are the clinical syndromes of E. tarda?
- primarily causes gastroenteritis, rare cases of septicemia
- GI dz include:
- acute, self-limiting gastroenteritis with watery diarrhea
- typhoid-like illness with bloody diarrhea and possible fever, nausea, vomiting, colonic ulcerations and terminal ileum nodularity
- has been mistaken for salmonellosis and inflammatory bowel dz (Crohn’s dz)
Tribe III: SalmonellEAE
- Salmonella, all serotypes are considered a single species
- it takes a LOT to cause infection
habitat: lower animals (poultry, chickens, turkeys, cows, pigs, pets) for NONtyphoid strains (Humans for S. typhi)
What are the 5 main characteristics of Salmonella?
- NON-lactose fermenter
- produces hydrogen sulfide (black)
- transmission via improper food handling
- found in humans (S. typhi) and livestock
- secondary transmission person-to-person
What is the incidence and mode of transmission of Salmonella?
- ~1.4 million cases/yr in US, 16k hospitalizations and 600 deaths
- ~35k typed by PH labs
- ~1/2 Salmonela epidemics are result of contaminated poultry and poultry products
- also associated with reptiles (lizards, snakes, turtles)
5 Salmonella Clinical Syndromes
- Asymptomatic (carrier) stat
- Febrile Gastroenteritis
- Enteric Fever
- Septicemia
- Focal Infections
Asymptomatic (carrier) state-Salmonella
- relatively limited with non-S. typhi, occasionally prolonged over a year.
- chronic or decades long with S. typhi
Febrile Gastroenteritis-Salmonella
- most common presentation in man
- fond in 2/3 of pts with culture confirmed Salmonella infections
- incubation: 12-48 hrs
- Symptoms: malaise, nausea, sometimes with vomiting, followed by abdominal pain and diarrhea
- self-limited, duration 3-5 days
- dont want to treat because dont want to destroy food flora, its needed to re-establish intestinal health and dont want to cause AB resistance
Enteric Fever-Salmonella
- prolonged, serious illness, best known example: Typhoid fever
- caused by S. typhi and S. paratyphi A and B, rare with other serotypes
- incubation: 1-2 weeks
- illness duration: 4 weeks characterized by increasing fever for 2 wees (bactermic stage) followed by GI symptoms for 1-2 wks
- only known reservoir of S. typhi is man
- usally in aread with poor sanitation (India, Indonesia)
Septicemia-Salmonella
- without major GI involvement-characteristically found in pts with underlying leukemia, lymphoma, AIDS, SLE, sickle cell crisis, and alcoholic hepatitis
- found frequently in infections due to S. choleraesuis, S. dublin, and S. oranienburg
- relapses are common
Focal Infections-Salmonella
- Osteomyelitis
- Meningitis
- Brain Ascess
- Endocarditis
- gets in the blood then disseminated to some distant site
Pathogenesis of Enteric Fever-Salmonella
- bacteria bind to M cells
- infection kills cell, bacteria go to Peyer’s patches
- organisms invade macrophages where they multiply
- inhibition of oxidative metabolic burst allows organism to survive intracellularly
- bacteria spread drom Peyer’s patches–>RE (reticular endothelium)–>bloodstream
- LPS acts as a major virulence factor causing septic shock
- immunity is humoral and cell-mediated
- S. typhi occurs only in humans
- transmission person-to-person
- *always get blood and stook if unsure what stage theyre in (it is BI-MODAL)
Path of Gastroenteritis-Salmonella
- Salmonella produces an adhesion–>stimulates rearrangement of plasma cell membrane to form ruffles
- bacteria enter cell by pinocytosis associated with ruffles
- organism invade large and small bowel and lamina propria
- large inflammatory response induced
Clinical Manifestations of Enteric Fever-Salmonella
-presents with fever, headache, rose spots, constipation
-rose spots; pink macules or prupuric lesions
-fever; temperature-pulse dissociation (refers to relative bradycardia with a pulse rate less than expected at a given body temp. associated with specific infection, including intracellular organisms such as salmonella, legionella, and chlamydia)
-neuropyschiatric manifestations
-Complications:
»GI bleeding
» Perforation of ileal ulcers
»circulatory collapse
»relapse following treatment
»asymptomatic long term carriage
Clinical Manifestations of Bacteremia-Salmonella
-increased risk in peds, geriatric, AIDS pts
-clinically similar to other gram NEG bacteremias
-10% localized suppurative infections
»osetomyelitis, endocarditis, arthritis
-diagnosed by positive blood cultures
-Rx: 3rd generation cephalosporin
Tribe IV-CitrobacterEAE
Genus Citrobater: C. freundii, C. koseri
Habitat: intestinal tract humans/animals
What are the clinical syndromes of Citrobacter?
- nosocomial infections of urinary and respiratory tracts of debilitated, hospitalized pts, endocarditis, and hospital acquired bacteremias
- C. freundii=rare cause of diarrhea
- C. koseri=rare cause of meningitis and brain abscess in neonates
Tribe 5-KlebsiellEAE-Genus Klebsiella
*K. pneumoniae, K. oxytoca, (K. ozaenae, K. rhinoscleromatic)
Habitat: intestines and upper respiratory tract of humans and animals
Klebsiella Clinical Syndromes: K. pneuoniae and K. oxytoca
oxy: POSITIVE indol, penumoniae: NEG indol
- primary lobar penumoni characterized by destructive changes, necrosis, and hemorrhage (“currant jelly” sputum), bronchopneumonia, bronchitis, accounts for 9% of UTIs and 14% of bacteremias in hospitalized pts
What are the 5 organisms responsible for NEONATAL MENINGITIS??
1. 2. C. koseri 3. 4. 5.
Klebsiella Clinical Syndromes: K ozaenae and K. rhinoscleromatis
K. ozaenae-atrophic rhinitis (ozena), destruction of mucosa and fetid mucopurulent discharge from nose
K. rhinoscelromatis-rhinoscleroma, chronic granulomatous dz involving mucosa of upper respiratory tract
Tribe 5-KlebsiellEAE-Genus Enterobacter
*E. aerogenes, E. cloacae
Habitat: widely distributed in the environment and GI tract of humans
What are the clinical syndromes of Enterobacter?
- frequent colonizers of hospital patients (**nosocomial infections), cause opportunistic infections involving urinary tract, respiratory tract, cutaneous wounds, occasional cause of septicemia and meningitis
- antibiotic therapy can be ineffective, because the organism are frequently resistant to multi antibiotics
Tribe 5-Klebsielleae-Genus Serratia
*S. marcescens
Habitat: widely distributed in the environment
on MacConkey, show RED-pigmented colonies
What are the clinical syndromes of Serratia?
- nosocomial infections, pneumoniae, septicemia, UTI, surgical wound and cutaneous infections
- also reported as a cause of endocarditis and osteomyelitis in IV drug addicts
Tribe 6-ProeEAE-Genus Proteus
*P. mirabilis (indol NEGATIVE), P. vulgaris (indol POSITIVE)
Key ID features: **swarming observed on blood agar, lactose NEG on MacConkey, STRONGLY urease POSITIVE
Habitat: soil, water and intestinal tract of humans and animals
What are the clinical syndromes of Proteus?
- second to E. coli in frequency of isolation in the clinical lab
- P. mirabilis is most frequently isolated species, cause of UTIs and wound infections
- strongly urease POSITIVE produces highly alkaline urea which can lead to renal calculi (renal stones)
- composed of struvite (Mg ammonium PO4)
- P. vulgaris is most commonly recovered from infected sites of immunocompromised pts
How many species are there of Genus Yersinia?
There are 11 species, the most important of which are Y. pesits–>responsible for the bubonic plague and Y. enterocolitica
What are the key Identifying Features in Y. enterocolitica
- pinpoint colonies on MacConkey blood agar plate at 24hrs
- biochemical tests should be incubated at 25 C (grow better at cool temperature)
- urease POSITIVE
- lactose NEGATIVE, G (-)
What is the epidemiology of Y. enterocolitica?
- most common spp in clinical specimens
- widely distributed in lakes and reservoirs (adapted to environments with cooler temps)
- epizootic outbreaks of diarrhea, lymph-adenopathy, pneumonia, and spontaneous abortions occur in various animals
- over 50 serogroups, O:3** serotype infecting humans
- pigs=major reservoir for infection in humans
- diarrheal illness assoc with household prep of chitlins
- portal of entry: oral digestive route
What are the clinical syndromes of Y. enterocolitica?
- orgs adhere to and penetrate the ileum, causing terminal ileitis, lymphadenitis, and acute enterocolitis.
- mimics appendicitis and most common in children
- enterocolitis accounts for 2/3 of infection. Diarrhea, fever, abdominal pain lasting 1-2 weeks.
- chronic form can persist months to >1yr.
- also associated with blood transfusios related sepsis, arthritis, intra-abdo abscess, hepatitis, osteomyelitis
- blood contamination occurs due to asymptomatic Y. enterocolitica bactermemia at time of blood donation
- Y. enterocolitica can proliferate in blood stored at 4 C after 2-3 weeks
