Enterobacteriaceae

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Enterobacteriaceae
Meningitis
Opportunistic pathogens Escherichia
coli Klebsiella pneumoniae Enterobacter
aerogenes Serratia marcescens Proteus
spp. Providencia spp. Citrobacter spp.
Pneumonia
Sepsis
Diarrhea
UTI
Obligate pathogens Salmonella spp. Shigella
spp. Yersinia spp. Some E. coli strains
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Morphology and Physiology
Klebsiella spp. have large capsule (form large
and very mucoid colonies) those of Enterobacter
have smaller capsule the others produce
diffusible slime layers (form circular, convex
and smooth colonies).
Short gram-negative rods. Facultative
anaerobes. Grow readily and rapidly on simple
media.
K. pneumoniae
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Some enteric bacteria are motile. Klebsiella
species are not motile, while Proteus species
move very actively by means of peritrichous
flagella, resulting in "swarming" on solid
medium. Some strains of E. coli produce
hemolysis on blood plates.
Proteus spp.
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Enterobacteriaceae is characterized biochemically
by the ability to reduce nitrates to nitrites and
to ferment glucose. Cytochrome oxidase-negative.
Enterobacteriaceae species differ in their
ability to ferment lactose. Some ferment lactose
rapidly, some does it slowly and the others
(e.g., Salmonella and Shigella) do not ferment
lactose at all. Some Enterobacteriaceae
pathogens (e.g., Salmonella and Shigella) are
resistant to bile salts, and this property can be
used to select them from commensal organisms that
are inhibited by bile salts.
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Antigenic Structure
O antigens O-specific polysaccharides located in
LPS. Heat-stable and resistant to alcohol. A
single organism may carry several O antigens.
(Core polysaccharide of LPS enterobacterial
common antigen) K antigens External to O antigens
in some strains. Mostly are capsular antigens
(polysaccharides). K antigens of Klebsiella can
be identified by capsular swelling test. H
antigen Flagellin. Heat-labile and denatured by
alcohol. May be absent or undergo phase variation
in different species.
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ECA
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Pathogenesis and Immunity
Common virulence factors
Endotoxin (Lipid A of LPS) Capsule Antigenic
phase variation Acquisition of growth factors
(e.g. Fe) Resistance to serum killing Antimicrobia
l resistance
Type III secretion systems possessed by some
Enterobacteriaceae pathogens, e.g., E. coli,
Yersinia, Salmonella, and Shigella facilitate
transport of bacterial virulence factors directly
into host cells.
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Toll-like receptor 4 (TLR-4)
Pathogenesis of sepsis caused by gram-negative
bacteria
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Pathophysiological effects of LPS Activation of
complement, release of cytokines, fever,
leukocytosis, thrombocytopenia, impaired organ
perfusion and acidosis, disseminated
intravascular coagulation (DIC), hypotension,
shock and death, premature labor and abortion.
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Escherichia coli
Pathogenesis and clinical diseases
Sepsis For people with inadequate host defenses,
e.g. the newborns. Usually originates from UT or
GI infections. Some infections may be endogenous.
Meningitis E. coli (particularly K1 strains) and
S. agalactiae are the leading causes of
meningitis in infants.
Bacteremia
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Escherichia coli
Pathogenesis and clinical diseases
Urinary tract infection E. coli is the most
common cause of urinary tract infection. Communit
y- vs. hospital-acquired UT infection Most
infections originate from colon the bacteria
contaminate the urethra, ascend into the bladder,
and may migrate into the kidney or
prostate. Symptoms urinary frequency, dysuria,
hematuria, and pyuria. Can result in bacteremia
and sepsis. Uropathogenic E. coli strains produce
P (Pyelonephritis-associated) pili, which is
associated with renal colonization and may induce
protective immunity, and hemolysin HlyA.
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Escherichia coli
Pathogenesis and clinical diseases
EAST PET
Gastroenteritis (Diarrhea) Caused by various
virotypes Enterotoxigenic E. coli Enteropathogeni
c E. coli Enterohemorrhagic E. coli Enteroinvasive
E. coli Enteroaggregative E. coli
ST
Table 30-2
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Escherichia coli
Pathogenesis and clinical diseases
Enterotoxigenic E. coli (ETEC) major causal
agent of Traveler's diarrhea. These strains
express a) Heat-labile (LT-1) enterotoxins an
A-B toxin. Subunit A causes intense and prolonged
hyper secretion of chloride ions and inhibits the
reabsorption of sodium and chloride. The gut
lumen is distended with fluid, and hypermotility
and secretory diarrhea occur, lasting for several
days. It stimulates the production of
neutralizing antibodies, and cross-reacts with
the enterotoxin of Vibrio cholerae. b)
Heat-stable (STa) enterotoxin also stimulates
fluid secretion poorly immunogenic short onset.
c) Colonization factors (CFAs) facilitate the
attachment of E. coli strains to intestinal
epithelium. Usually are pili in nature.
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ADP-ribosylation
Enhance chloride secretion Decrease sodium and
chloride absorption
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Escherichia coli
Pathogenesis and clinical diseases
Enteropathogenic E. coli (EPEC) causes infant
diarrhea in poor countries. Watery diarrhea
results from malabsorption due to microvilli
destruction. Spread by person-to-person contact.
Enteroinvasive E. coli (EIEC) closely related to
Shigella in pathogenic properties.
Enteroaggregative E. coli (EAEC) causes chronic
diarrhea and growth retardation in infants in
developing countries.
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Escherichia coli
Pathogenesis and clinical diseases
Enterohemorrhagic E. coli (EHEC) The most common
strains producing disease in developed
countries. These strains are associated with
hemorrhagic colitis and hemolytic uremic syndrome
(HUS acute renal failure, microangiopathic
hemolytic anemia and thrombocytopenia 5-10
infected children). Serotpe O157H7 is most
commonly isolated. Cattle is a reservoir, and
hamburger, unpasteurized milk, fruit juices, and
uncooked vegetables are common sources of human
infection. Induces A/E lesions on enterocytes.
Diarrhea and HUS may be associated with the Shiga
toxins, which are A-B toxins that bind to 28S
rRNA and disrupt protein synthesis.
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Other opportunistic Enterobacteriaceae
Klebsiella K. pneumoniae and K. oxytoca are the
most commonly isolated. Can cause
community-acquired primary lobar pneumonia
(frequently involves necrotic destruction of
alveolar space), and infections of wound, soft
tissue, and urinary tract. Risk factors for
pneumonia alcoholism compromised pulmonary
function. In Taiwan liver abscess is commonly
seen in infection by K. pneumoniae. K.
granulomatis may cuase granuloma inguinale, a
sexually transmitted disease, in some
countries. K. rhinoscleromatis granulomatous
disease of the nose. K. ozaenae chronic atrophic
rhinitis.
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Proteus Most common isolates P. mirabilis. Cause
urinary tract infections and bacteremia. Produce
urease, making the urine of the patients of UT
infection with Proteus alkaline, promoting stone
formation by precipitating Mg and
Ca. Enterobacter, Citrobacter, Morganella,
Serratia Opportunistic pathogens causing
nosocomial infections in neonates and
immunocompromised patients. These genera,
particularly Enterobacter, are resistant to
multiple antibiotics.
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Escherichia coli and other opportunistic
Enterobacteriaceae
Laboratory diagnosis
Smears the Enterobacteriaceae pathogens resemble
each other. The presence of large capsules is
suggestive Klebsiella. Culture blood agar and
selective differential media (e.g., MacConkey
agar), the latter is useful for preliminary
identification. Commercial biochemical test
systems can be used for identification of
Enterobacteriaceae members. Serologic tests are
used for determining the clinical significance of
an isolate and for epidemiologic purpose.
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E. coli and other opportunistic Enterobacteriaceae
Treatment
Variation in drug susceptibility is great, and
antibiotic sensitivity tests are essential.
Diarrhea patients usually need only symptomatic
relief. Antibiotic treatment may prolong the
fecal carriage or increase the risk of secondary
complications. Treatment of bacteremia and
septic shock prompt antibiotic treatment,
restoration of fluid and electrolyte balance, and
treatment of disseminated IV coagulation.
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E. coli and other opportunistic Enterobacteriaceae
Prevention and control Enterobacteriaceae are a
major part of normal flora and a common
contaminant of the environment. In hospitals,
opportunistic Enterobacteriaceae are commonly
transmitted by personnel, instruments, or
parenteral medications. Their control depends on
hand washing, rigorous asepsis, sterilization of
equipment, disinfection, restraint in IV therapy,
and strict precautions in keeping the urinary
tract sterile.
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Salmonella
Salmonella spp. do not ferment lactose. Most
species of Salmonella are motile with
peritrichous flagella. Some Salmonellae have
capsular antigens that of S. Typhi is referred
to as Vi antigen. Groups and species of
Salmonella are identified by serologic analysis
of O and H antigens (gt 2,500 serotypes).
Classification of salmonellae is traditionally
based on serogrouping and serotyping (e.g. S.
typhimurium, which is reclassified as S. enterica
together with most human pathogens by analysis of
DNA homology). The correct name for S. typhi is
S. enterica, serovar. Typhi or S. Typhi. They can
be identified by biochemical tests and
serogrouping, with follow-up serotyping
confirmation.
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Salmonella
Epidemiology
S. Typhi and S. Paratyphi are primarily infective
for humans. Other salmonellae are chiefly
pathogenic in animals (poultry, pigs, rodents,
cattle, pets etc.) that constitute the reservoir
for human infection. Humans usually become
infected by ingestion of contaminated food or
drink (mean infective dose 106-108, but that of
S. typhi is lower). In children, infections can
result from direct fecal-oral spread. The most
common sources of human infections poultry,
eggs, dairy products, and foods prepared on
contaminated work surfaces. However, the major
source of infection for enteric fever is the
carriers (convalescent or healthy permanent).
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Salmonella
Pathogenesis and Immunity
Invasion Acid tolerance response (ATR) gene
protects the organism from gastric acid. The
bacteria invade into (by inducing membrane
ruffling) and multiply in the M cells and
enterocytes of the small intestine. They can also
be transported across the enterocytes and
released into the blood and lymphatic
circulation. Inflammatory response confines the
infection to the GI tract in non-typhoid
salmonellosis. Survival in macrophages Salmonellae
are facultative intracellular pathogen.
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Salmonella
Clinical diseases
1. Enteritis Incubation period 6-48
hours. Symptoms nausea, headache, vomiting,
nonbloody profuse diarrhea, with few leukocytes
in the stools. Low-grade fever, abdominal cramp,
myalgia, and headache are also common. Episode
resolves in 2-7 days. Inflammatory lesions of the
small and large intestine are present. Stool
cultures remain positive for several weeks after
clinical recovery.
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Salmonella
Clinical diseases
2. Bacteremia Most common causal species S.
Choleraesuis, S Typhi and S. Paratyphi. Symptoms
like sepsis caused by other gram-negative
bacteria. 10 of patients may have localized
suppurative infections, e.g., osteomyelitis,
endocarditis, arthritis, etc. High risk
population pediatric and geriatric patients
AIDS patients.
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Salmonella
Clinical diseases
3. Enteric fever (typhoid fever) Causal species
S. Typhi, S. Paratyphi A, S. Schottmuelleri, and
S. Hirschfeldii. Mouth small intestine
lymphatics and bloodstream
infect liver, spleen and bone marrow
multiply and pass into the blood second
and heavier bacteremia onset of clinical
illness colonization of gallbladder
invasion of the intestine typhoid
ulcers and severe illness. Chronic carriers
(1-5 of patients) bacteria persist in the
gallbladder and the biliary tract for more than
one year.
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Symptoms incubation time 10-14 days. Gradually
increasing fever, malaise, headache, myalgias,
and anorexia, which persist for a week or longer.
In severe cases intestinal hemorrhage and
perforation. Principal lesions hyperplasia and
necrosis of lymphoid tissue, hepatitis, focal
necrosis of the liver, and inflammation of the
gallbladder, periosteum, lungs and other organs.
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Salmonella
Treatment
Enteric fever and bacteremia require antibiotic
treatment chloramphenicol, ampicillin,
trimethoprim-sulfamethoxazole. Surgical drainage
of metastatic abscesses may be required. Salmonell
a enterocolitis needs only supportive therapy
(antibiotic treatment may prolong the symptoms
and excretion of the salmonellae). Drugs to
control hypermotility of the gut should be
avoided because it is easy to transform a trivial
gastroenteritis into a life-threatening
bacteremia by paralyzing the bowel. Chronic
carriers of S. Typhi may be cured by antibiotics
alone or combined with cholecystectomy.
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Salmonella
Prevention and control Sanitary
measures. Carriers must not be allowed to work as
food handlers. Strict hygienic precautions for
food handling. Vaccines against S. Typhi
Purified Vi antigen Oral, live attenuated
vaccine.
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National salmonella death toll rises to 7 (Staff
writer Ridgely Ochs contributed to this story.
January 24, 2009) A seventh death was linked
Friday to a nationwide outbreak of salmonella
associated with tainted peanut butter and paste
sourced to the Peanut Corp. of America's plant in
Blakely, Ga., authorities confirmed. Although
their exact causes of death have not been
determined, all seven people have died after
being infected with the bacterial strain
Salmonella Typhimurium, the Centers for Disease
Control and Prevention said on its Web site.
There have been 493 cases reported in 43 states
and one Canadian province of people sickened,
though authorities stress the numbers sickened
are likely far in excess of that as many cases go
unreported. Known patients ranged in age from 1
to 98, and 22 percent of the those have been
hospitalized. Another 10 firms Friday recalled
products that use PCA peanut butter or paste -
bringing to roughly 360 the number of products
affected - as it emerged that the Peanut Corp. of
America's plant in Blakely, Ga. laid off most of
its roughly 50 workers. The outbreak has
triggered a congressional inquiry and renewed
calls for reform of food safety laws.
http//www.newsday.com/services/newspaper/printedi
tion/saturday/health/ny-lisalm246010666jan24,0,587
6138.story
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Shigella
S. dysenteriae, S. flexneri , S. sonnei , S.
boydii bacillary dysentery gt 45 O serotypes
have no H antigen do not ferment lactose.
Pathogenesis and Immunity Shigellosis is
primarily a pediatric disease, and is restricted
to the GI tract. Mean infective dose 103. Mouth
colon invade M cells and
subsequently spread to mucosal epithelial cells
cause microabscess in the wall of colon and
terminal ileum necrosis of the mucous
membrane, superficial ulceration, bleeding, and
formation of pseudomembrane. Shiga toxin An A-B
toxin inhibiting protein synthesis. Damages
intestinal epithelium and glomerular endothelial
cells (associated with HUS) .
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Destablize the intestinal wall
Activates the invasion genes on the virulence
plasmid
M cell
Internalized shigellae induce apoptosis of
macrophage and release of the bacteria
Attracted by the cytokines released by macrophage
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Shigella
Clinical diseases Incubation period 1-3
days Sudden onset of abdominal pain, fever and
watery diarrhea number of stools
increase, less liquid, often contain mucus and
blood, rectal spasms with resulting lower
abdominal pain (tenesmus) symptoms subside
spontaneously in 2-5 days in adult cases, but
loss of water and electrolytes frequently occur
in children and the elderly a small number
of patients remain chronic carriers. Some cases
were accompanied by hemolytic uremic syndrome
(HUS).
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Shigella
Laboratory diagnosis Specimens fresh stool,
mucus flecks, and rectal swabs. Large numbers of
fecal leukocytes and some RBC may often be seen
microscopically. Culture differential and
selective media as used for salmonellae. Treatment
Antibiotic treatment chloramphenicol,
ampicillin, tetracycline, and trimethoprim-sulfame
thoxazole. Drug resistance is common. Opiates
should be avoided.
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Shigella
Prevention and control Humans are the only
reservoir for shigellae. Transmission of
shigellae water, food, fingers, feces, and
flies. Most cases occur in children under 10
years of age. Prevention and control of
dysentery 1. Sanitary control of water, food and
milk sewage disposal and fly control. 2.
Isolation of patients and disinfection of
excreta. 3. Detection of subclinical cases and
carriers.
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Yersinia
Y. pestis plague ("black death") Y.
pseudotuberculosis and Y. enterocolitica
gastroenteritis
Grows more rapidly in media containing blood or
tissue fluids and fastest at 30 oC. Some species
(e.g. Y. enterocolitica) can grow in refrigerated
food. Pathogenesis The Yersinia pathogens are
able to resist phagocytic killing by secreting
proteins into the phagocyte and result in
inhibition of killing by phagocyte, apoptosis of
macrophage, and suppression of cytokine
production. Y. pestis produces a protein capsule
(Fraction 1), and Pla (plasminogen activator
protease) that degrades C3b and C5a, and fibrin
clot (enhances spread of bacteria into blood
stream).
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Yersinia pestis
Causes zoonotic infections humans are accidental
hosts. Three major pandemics have occurred in 541
AD, 1320s and 1860s. Two forms of
infections Urban plague Rats as natural
reservoirs. Spread among rats or between rats
and humans by infected flea. Can be eliminated
by effective control of rats and better
hygiene. Sylvatic plague infections of rodents
and domestic cats. Y. pestis are widely
distributed in mammalian reservoirs and flea
vectors and produces fatal infections in animal
reservoirs. Human infections are acquired by
contacting the reservoir population.
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Yersinia pestis
Pathogenesis Bubonic plague Y. pestis enters a
flea when it feeds on an infected animal
the bacteria multiply in the gut of the flea
flea becomes hungry and bites ferociously
Y. pestis passes from the flea into the bite
wound the bacteria are phagocytised, but
can multiply intracellularly or extracellularly
reach the lymphatics, and an intense
hemorrhagic inflammation develops in the enlarged
lymph nodes, which may undergo necrosis Y.
pestis may reach the bloodstream and become
widely disseminated. Hemorrhagic and necrotic
lesions may develop in all organs. Primary
pneumonic plague Results from inhalation of
infective droplets (usually from a coughing
patient), with hemorrhagic consolidation of the
lung, sepsis and death.
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Yersinia pestis
Clinical Diseases Bubonic plague Incubation
period 2-7 days. High fever and painful
lymphoadenopathy with greatly enlarged, tender
lymph nodes (buboes) in the groin and axilla
sepsis (early stage vomiting and diarrhea
late stage hypotension, renal and cardiac
failure terminal stage pneumonia and
meningitis). Mortality 75 if untreated. Pneumoni
c plague Incubation time 2-3 days. Fever and
malaise, pulmonary signs develop within 1 day.
Patients are highly infectious. Mortality 90 if
untreated.
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Yersinia pestis
Treatment Patients have to be promptly treated
with antibiotics (drug of choice
streptomycin). Epidemiology and control Plague is
an infection of wild rodents that still occurs in
many parts of the world (enzootic areas India,
Southeast Asia, Africa, and North and South
America). Control of plague requires surveys of
infected animals, vectors, and human contacts,
and by destruction of infected animals. All
patients with suspected plague should be
isolated. Contacts of patients with suspected
pneumonic plague should receive tetracycline as
chemoprophylaxis.
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Y. enterocolitica and Y. pseudotuberculosis
Cause zoonotic infections. Y. enterocolitica is a
common cause of enteritis in cold areas during
the cold months. Y. pseudotuberculosis infection
is relatively uncommon. They are found in the
intestine of a variety of animals, and are
transmissible to humans through contaminated
food, drink or fomites, resulting in diarrhea,
fever and abdominal pain that last for 1-2 weeks
or, in some cases, months. Most are self-limited.
Y. enterocolitica infection can cause
pseudoappendicitis (enlarged mesenteric lymph
nodes) in children, and blood-transfusion related
sepsis in those who used blood products stored
for at least 4 weeks.
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Y. enterocolitica grows slowly at 37 oC and
prefers cooler temperatures. The fecal specimen
can be mixed with saline and then store at 4 oC
for 2 weeks or more to facilitate isolation of
this organism (cold enrichment).
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How does Proteus swarm?
45
Lipopolysaccharide (LPS) is also called
endotoxin. LPS is composed of lipid A, core
polysaccharide, and O-specific polysaccharide. Lip
id A anchors LPS in the lipid bilayer. It causes
symptoms associated with endotoxin. O-specific
polysaccharide can be used to identify certain
species and strains.
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