Person-to-person spread by fecal-oral route,

especially

in overcrowded areas, group settings (e.g., daycare)

and areas with poor sanitary conditions

Only found in humans at times of

infection; not part of normal

bowel flora

Shigella spp

Person-to-person spread by fecal-oral route by

ingestion of food or water contaminated with human

excreta

Only found in humans but not

part

of normal bowel flora

Salmonella serotype

Typhi

Salmonella serotypes

Paratyphi A, B, C

Ingestion of contaminated food products processed

from animals, frequently of poultry or dairy origin.

Direct person-to-person transmission by fecal-oral

route can occur in health care settings when

hand-washing guidelines are not followed

. Widely disseminated

in nature and

associated with various animals

Other Salmonella spp

Uncertain; probably by ingestion of contaminated

water

or close contact with carrier animal

Gastrointestinal tract of coldblooded

animals, such as reptiles

Edwardsiella tarda

Yersinia pestis Carried by urban and domestic From rodents to humans by the bite of flea vectors or

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Pathogenesis and spectrum of diseases:

 The clinically relevant members of the Enterobacteriaceae can be considered as two groups: the opportunistic

pathogens and the intestinal pathogens.

 Typhi and Shigella spp. are among the latter group and are causative agents of typhoid fever and dysentery,

respectively. Yersinia pestis is not an intestinal pathogen, but it is the causative agent of plague. The

identification of these

organisms in clinical material is serious and always significant. These organisms, in addition to others, produce

various potent virulence factors and can cause life threatening infections (Table 2). The opportunistic pathogens

most commonly include Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., and a

variety of other organisms. Although considered opportunistic pathogens, these organisms produce significant

virulence factors, such as endotoxins capable of mediating fatal infections.

by ingestion of contaminated animal tissues; during

human epidemics of pneumonic (i.e., respiratory)

disease, the organism can be spread directly from

human to human by inhalation of contaminated

airborne droplets; rarely transmitted by handling or

inhalation of infected animal tissues or fluids

rats

and wild rodents, such as the

ground squirrel, rock squirrel, and

prairie dog

Consumption of incompletely cooked food products

(especially pork), dairy products such as milk, and,

less commonly, by ingestion of contaminated water

or by contact with infected animals

 Dogs, cats, rodents,

rabbits, pigs,

sheep, and cattle; not part of

normal human microbiota

Yersinia

enterocolitica

Ingestion of organism during contact with infected

animal or from contaminated food or water

Rodents, rabbits, deer, and birds;

not

part of normal human microbiota

Yersinia

pseudotuberculosis

Endogenous or person-to-person spread, especially in

hospitalized patients

Normal human gastrointestinal

microbiota

Citrobacter spp.,

Enterobacter spp.,

Klebsiella spp.,

Morganella spp.,

Proteus

spp., Providencia

spp., and Serratia spp

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However, because they generally do not initiate disease in healthy, uncompromised human hosts, they are

considered opportunistic.

Although E. coli is a normal bowel inhabitant, its pathogenic classification is somewhere between that of the

overt pathogens and the opportunistic organisms. Diuretic strains of this species, such as enterotoxigenic

E. coli (ETEC), enteroinvasive E. coli (EIEC), and enteroaggregative E. coli (EAEC), express potent toxins and

cause serious gastrointestinal infections. Additionally, in the case of enterohemorrhagic E. coli (EHEC) also

referred to as verocytotoxin producing E. coli (VTEC) or Shiga-like toxin producing E. coli (STEC), the

organism may produce life-threatening systemic illness. Furthermore, as the leading cause of

Enterobacteriaceae nosocomial infection, E. coli is likely to have greater virulence capabilities than the other

species categorized as “opportunistic” Enterobacteriaceae.

Table (1-2 )Pathogenesis and Spectrum of Disease for Clinically Relevant Enterobacteriaceae

Organism Virulence Factors Spectrum of Disease and Infections

Escherichia coli

(as a cause of

extraintestinal

infections)

Several, including endotoxin,

capsule

production pili that mediate

attachment to host cells

Urinary tract infections, bacteremia, neonatal

meningitis, and

nosocomial infections of other various body sites.

Most common

cause of gram-negative nosocomial infections.

Enterotoxigenic

E. coli

(ETEC)

Pili that permit gastrointestinal

colonization. Heat-labile (LT)

and

heat-stable (ST) enterotoxins

that

mediate secretion of water and

electrolytes into the bowel

lumen

Traveler’s and childhood diarrhea, characterized by

profuse, watery

stools. Transmitted by contaminated food and water.

Enteroinvasive

E. coli (EIEC)

Virulence factors uncertain, but

organism invades enterocytes

lining

the large intestine in a manner

nearly

identical to Shigella

Dysentery (i.e., necrosis, ulceration, and

inflammation of the large

bowel); usually seen in young children living in

areas of poor

sanitation.

Enteropathogenic

E. coli (EPEC)

Bundle-forming pilus, intimin,

and other

factors that mediate organism

attachment to mucosal cells of

the

small bowel, resulting in

Diarrhea in infants in developing, low-income

nations; can cause a

chronic diarrhea.

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Section I– Microbiology By Dr. Mohammed Ayad

changes in

cell surface (i.e., loss of

microvilli

Enterohemorrhagic

E. coli (EHEC,

VTEC, or STEC)

Toxin similar to Shiga toxin

produced by

Shigella dysenteriae. Most

frequently

associated with certain

serotypes,

such as E. coli O157:H7

Inflammation and bleeding of the mucosa of the

large intestine (i.e.,

hemorrhagic colitis); can also lead to hemolyticuremic syndrome,

resulting from toxin-mediated damage to kidneys.

Transmitted by

ingestion of undercooked ground beef or raw milk.

Enteroaggregative

E. coli (EAEC)

Probably involves binding by

pili, ST-like,

and hemolysin-like toxins;

actual

pathogenic mechanism is

unknown

Watery diarrhea that in some cases can be prolonged.

Mode of

transmission is not well understoo

Shigella spp. Several factors involved to

mediate

adherence and invasion of

mucosal

cells, escape from phagocytic

vesicles, intercellular spread,

and

inflammation. Shiga toxin role

in

disease is uncertain, but it does

have

various effects on host cells.

Dysentery defined as acute inflammatory colitis and

bloody diarrhea

characterized by cramps, tenesmus, and bloody,

mucoid stools.

Infections with S. sonnei may produce only watery

diarrhea

Salmonella serotypes Several factors help protect

organisms

from stomach acids, promote

attachment and phagocytosis

by

intestinal mucosal cells, allow

survival

in and destruction of

phagocytes, and

facilitate dissemination to other

Three general categories of infection are seen:

• Gastroenteritis and diarrhea caused by a wide

variety of serotypes

that produce infections limited to the mucosa and

submucosa of the

gastrointestinal tract. S. serotype Typhimurium and

S. serotype

Enteritidis are the serotypes most commonly

associated with

Salmonella gastroenteritis in the United States.

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tissues. • Bacteremia and extraintestinal infections occur by

spread from

the gastrointestinal tract. These infections usually

involve

S. Choleraesuis or S. dublin, although any serotype

may cause these

infections.

• Enteric fever (typhoid fever, or typhoid) is

characterized by prolonged

fever and multisystem involvement, including blood,

lymph nodes,

liver, and spleen. This life-threatening infection is

most frequently

caused by S. serotype Typhi; more rarely, S.

serotypes Paratyphi A, B

or C.

Yersinia pestis Multiple factors play a role in

the

pathogenesis of this highly

virulent

organism. These include the

ability to

adapt for intracellular survival

and

production of an

antiphagocytic

capsule, exotoxins, endotoxins,

coagulase, and fibrinolysin

Two major forms of infection are bubonic plague

and pneumonic

plague. Bubonic plague is characterized by high

fever and painful

inflammatory swelling of axilla and groin lymph

nodes (i.e., the

characteristic buboes); infection rapidly progresses to

fulminant

bacteremia that is frequently fatal if untreated.

Pneumonic plague

involves the lungs and is characterized by malaise

and pulmonary

signs; the respiratory infection can occur as a

consequence of

bacteremic spread associated with bubonic plague or

can be

acquired by the airborne route during close contact

with other

pneumonic plague victims; this form of plague is

also rapidly fatal.

Yersinia

enterocolitica

subsp.

Various factors encoded on a

virulence

plasmid allow the organism to

Enterocolitis characterized by fever, diarrhea, and

abdominal pain; also

can cause acute mesenteric lymphadenitis, which

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enterocolitica attach

to and invade the intestinal

mucosa

and spread to lymphatic tissue.

may present

clinically as appendicitis (i.e., pseudoappendicular

syndrome).

Bacteremia can occur with this organism but is

uncommon

Yersinia

pseudotuber

culosis

Similar to those of Y.

enterocolitica

Causes infections similar to those described for Y.

enterocolitica but is

much less common

Citrobacter spp.,

Enterobacter spp.,

Klebsiella spp.,

Morganella spp.,

Proteus spp.,

Providencia spp.,

and Serratia spp.

Several factors, including

endotoxins,

capsules, adhesion proteins,

and

resistance to multiple

antimicrobial

agents

Wide variety of nosocomial infections of the

respiratory tract, urinary

tract, blood, and several other normally sterile sites;

most frequently

infect hospitalized and seriously debilitated patients

SPECIFIC ORGANISMS:

OPPORTUNISTIC HUMAN PATHOGENS

Citrobacter spp. (C. freundii, C. koseri, C. braakii) Citrobacter organisms are inhabitants of the intestinal

tract.The most common clinical manifestation in patients as a result of infection occurs in the urinary tract.

However,additional infections, including septicemias, meningitis, brain abscesses, and neurologic

complications, have been person to person. Table 3 provides an outline of the biochemical differentiation of

the most common clinically isolated Citrobacter species. C. freundii may harbor inducible AmpC genes that

encode resistance to ampicillin and first-generation cephalosporins.

Table(3) Biochemical Differentiation of Citrobacter Species

Species Indole ODC Malonate ACID

FERMENTATIO

N

Adonitol

Dulcitol Melibiose Sucrose

C. braakii v pos neg Neg v v neg

C. freundii v neg neg Neg neg pos v

C. koseri pos pos pos Pos v neg v

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From Versalovic J: Manual of clinical microbiology, ed 10, 2011, Washington, DC, ASM Press.neg, Negative

< 15%; ODC, ornithine decarboxylase; pos, positive ≥ 85%; V, variable 15% to 84%.

Cronobacter sakazakii

Cronobacter sakazakii, formerly Enterobacter sakazakii, is a pathogen associated with bacteremia, meningitis,

and necrotizing colitis in neonates. The organism produces a yellow pigment that is enhanced by incubation at

25°C.

C.sakazakii may be differentiated from Enterobacter spp. As Voges-Proskauer, arginine dihydrolase, ornithine

decarboxylase positive. In addition, the organism displays the following fermentation reactions: D-sorbitol

negative, raffinose positive, L-rhamnose positive, melibiose positive, D-arabitol negative, and sucrose positive.

C. sakazakii is intrinsically resistant to ampicillin and first- and secondgeneration cephalosporins as a result of

an inducible AmpC chromosomal β-lactamase. Mutations to the AmpC gene may result in overproduction of βlactamase, conferring resistance to third-generation cephalosporins.

Edwardsiella tarda

Edwardsiella tarda is infrequently encountered in the clinical laboratory as a cause of gastroenteritis. The

organism is typically associated with water harboring fish or turtles. Immunocompromised individuals are

particularly susceptible and may develop serious wound infections and myonecrosis. Systemic infections occur

in patients with underlying liver disease or conditions resulting in iron overload. Enterobacter spp.

(E. aerogenes, E. cloacae, E. gergoviae, E. amnigenus, E. taylorae)

 Enterobacter spp. are motile lactose fermenters that produce mucoid colonies. Enterobacter spp. are reported

as one of the genera listed in the top 10 most frequently isolated health care–associated infections by the

National Healthcare Safety Network. The infections are typically associated with contaminated medical

devices, such as

respirators and other medical instrumentation. The organism has a capsule that provides resistance to

phagocytosis. Enterobacter spp. may harbor plasmids that encode multiple antibiotic resistance genes, requiring

antibiotic susceptibility testing to identify appropriate therapeutic options.

Escherichia coli (UPEC, MNEC, ETEC, EIEC, EAEC, EPEC and EHEC)

Molecular analysis of E. coli has resulted in the classification of several pathotypes as well as commensal

strains. The genus consists of facultative anaerobic, glucosefermenting, gram-negative, oxidase-negative rods

capable

of growth on MacConkey agar. The genus contains motile (peritrichous flagella) and nonmotile bacteria. Most

E. coli strains are lactose fermenting, but this function may be delayed or absent in other Escherichia spp.

Isolates of extraintestinal E. coli strains have been grouped into two categories: uropathogenic E. coli (UPEC)

and meningitis/sepsis–associated E. coli (MNEC).

UPEC strains are the major cause of E. coli–associated urinary tract infections. These strains contain a variety

of pathogenicity islands that code for specific adhesions and toxins capable of causing disease, including

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cystitis and acute pyelonephritis. MNEC causes neonatal meningitis that results in high morbidity and

mortality. Eighty percent of MNEC strains test positive for the K1 antigen.

The organisms are spread to the meninges from a blood infection and gain access to the central nervous system

via membrane-bound vacuoles in microvascular endothelial cells.

As mentioned, intestinal E. coli may be classified as enterohemorrhagic (or serotoxigenic [STEC], or

verotoxigenic [VTEC]), enterotoxigenic, enteropathogenic, enteroinvasive, or enteroaggregative. EHEC is

recognized

as the cause of hemorrhagic diarrhea, colitis, and hemolytic uremic syndrome (HUS). HUS, which is

characterized by a hemolytic anemia and low platelet

count, often results in kidney failure and death. Unlike in dysentery, no white blood cells are found in the stool.

Although more than 150 non-O157 serotypes have been associated with diarrhea or HUS, the two most

common

are O157:H7 and O157:NM (nonmotile). The O antigen is a component of the lipopolysaccharide of the outer

membrane, and the H antigen is the specific flagellin associated with the organism. ETEC produces a heatlabile

enterotoxin (LT) and a heat-stable enterotoxin (ST) capable of causing mild watery diarrhea. ETEC is

uncommon in the United States but is an important

pathogen in young children in developing countries.

EIEC may produce a watery to bloody diarrhea as a result of direct invasion of the epithelial cells of the colon.

Cases are rare in the United States. EPEC typically does not produce exotoxins. The pathogenesis of these

strains is associated with attachment and effacement of the intestinal cell wall through specialized adherence

factors. Symptoms of infection include prolonged, nonbloody diarrhea; vomiting; and fever, typically in infants

or children.

EAEC has been isolated from a variety of clinical cases of diarrhea. The classification as aggregative results

from the control of virulence genes associated with aglobal aggregative regulator gene, AggR, responsible for

cellular adherence. EAEC-associated stool specimens typically are not bloody and do not contain white blood

cells. Inflammation is accompanied by fever and abdominal pain.

Ewingella americana

Ewingella americana has been identified from blood and wound isolates. The organism is biochemically

inactive, and currently no recommended identification scheme has been identified.

Hafnia alvei

Hafnia alvei (formerly Enterobacter hafniae) has been associated with gastrointestinal infections. The

organism, resides in the gastrointestinal tract of humans and many animals It is a motile non–lactose fermenter

and is often

isolated with other pathogens. Most infections with H.alvei are indentified in patients with severe underlying

disease (e.g., malignancies) or after surgery or trauma.

However, a distinct correlation with clinical signs and symptoms has not been clearly developed, probably

because of the lack of identified clinical cases. Treatment is based on antimicrobial susceptibility testing.

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Klebsiella spp. (K. pneumoniae, K. oxytoca)

Klebsiella spp. are inhabitants of the nasopharynx and gastrointestinal tract. Isolates have been identified in

association with a variety of infections, including liver abscesses, pneumonia, septicemia, and urinary tract

infections. Some strains of K. oxytoca carry a heatlabile cytotoxin, which has been isolated from patients who

have developed a self-limiting antibiotic-associated

community-acquired pyogenic liver abscess worldwide.

All strains of K. pneumoniae are resistant to ampicillin. In addition, they may demonstrate multiple antibiotic

resistance patterns from the acquisition of multidrug-resistant plasmids, with enzymes such as carbapenemase.

Morganella spp. (M. morganii, M. psychrotolerans)

Morganella spp. are found ubiquitously throughout the environment and are often associated with stool

specimens collected from patients with symptoms of diarrhea.

They are normal inhabitants of the gastrointestinal tract. M. morganii is commonly isolated in the clinical

laboratory; however, its clinical significance has not been clearly defined. Morganella spp. are deaminase

positive and urease positive.

Pantoea agglomerans

Pantoea agglomerans appears as a yellow-pigmented colony and is lysine, arginine, and ornithine negative. In

addition, the organism is indole positive and mannitol, raffinose, salicin, sucrose, maltose, and xylose negative.

The organism is difficult to identify using commercial or traditional biochemical methods due to the high

variability of expression in the key reactions. Sporadic infections can occur due to trauma from objects

contaminated with