GRAM NEGATIVE RODS –

ENTERIC TRACT
 Introduction
• Gram-negative rods related to the enteric
tract include a large number of genera.
• These genera have therefore been divided
into three groups depending on the major
anatomic location of disease, namely, (1)
pathogens both within and outside the
enteric tract, (2) pathogens primarily
within the enteric tract, and (3) pathogens
outside the enteric tract
 Escherichia
Diseases
• E. coli is the most common cause of
urinary tract infection and gram-negative
rod sepsis. It is one of the two important
causes of neonatal meningitis and the agent
most frequently associated with "traveler's
diarrhea," a watery diarrhea.
• Some strains of E. coli are
enterohemorrhagic and cause bloody
diarrhea.
Important Properties
• E. coli is a straight gram-negative rod, in
contrast to the curved gram-negative rods
of the genera Vibrio, Campylobacter, and
Helicobacter.
• E. coli is the most abundant facultative
anaerobe in the colon and feces. It is,
however, greatly outnumbered by the
obligate anaerobes such as Bacteroides.
Pathogenesis
• The reservoir of E. coli includes both
humans and animals. The source of the E.
coli that causes urinary tract infections is
the patient's own colonic flora that
colonizes the urogenital area.
• The source of the E. coli that causes
neonatal meningitis is the mother's birth
canal; the infection is acquired during birth.
• In contrast, the E. coli that causes traveler's
diarrhea is acquired by ingestion of food or
water contaminated with human feces.
• E. coli has several clearly identified
components that contribute to its ability to
cause disease: pili, a capsule, endotoxin,
and three exotoxins (enterotoxins), two
that cause watery diarrhea and one that
causes bloody diarrhea and hemolytic-
uremic syndrome.
Clinical Findings
• E. coli causes a variety of diseases both
within and outside the intestinal tract. It is
the leading cause of community-acquired
urinary tract infections.
• These infections occur primarily in women;
this finding is attributed to three features
that facilitate ascending infection into the
bladder, namely, a short urethra, the
proximity of the urethra to the anus, and
colonization of the vagina by members of
the fecal flora.
• It is also the most frequent cause of
nosocomial (hospital-acquired) urinary
tract infections, which occur equally
frequently in both men and women and
are associated with the use of indwelling
urinary catheters.
• E. coli is also a major cause, along with the
group B streptococci, of meningitis and
sepsis in neonates.
• Diarrhea caused by enterotoxigenic E. coli
is usually watery, nonbloody, self-limited,
and of short duration (1–3 days). It is
frequently associated with travel.
Laboratory Diagnosis
• Specimens suspected of containing enteric
gram-negative rods, such as E. coli, are
grown initially on a blood agar plate and
on a differential medium, such as EMB agar
or MacConkey's agar. E. coli, which
ferments lactose, forms pink colonies,
whereas lactose-negative organisms are
colorless.
Treatment
• Treatment of E. coli infections depends on
the site of disease and the resistance
pattern of the specific isolate.
• For example, an uncomplicated lower
urinary tract infection can be treated for
just 1 to 3 days with oral trimethoprim-
sulfamethoxazole or an oral penicillin, e.g.,
ampicillin.
Prevention
• There is no specific prevention for E. coli
infections, such as active or passive
immunization. However, various general
measures can be taken to prevent certain
infections caused by E. coli and other organisms.
• For example, the incidence of urinary tract
infections can be lowered by the judicious use
and prompt withdrawal of catheters and, in
recurrent infections, by prolonged prophylaxis
with urinary antiseptic drugs, e.g., nitrofurantoin
or trimethoprim-sulfamethoxazole.
 Salmonella
Diseases
• Salmonella species cause enterocolitis,
enteric fevers such as typhoid fever, and
septicemia with metastatic infections such
as osteomyelitis.
Pathogenesis & Epidemiology
• The three types of Salmonella infections
(enterocolitis, enteric fevers, and
septicemia) have different pathogenic
features.
1. Enterocolitis is characterized by an
invasion of the epithelial and subepithelial
tissue of the small and large intestines.
2. In typhoid and other enteric fevers,
infection begins in the small intestine but
few gastrointestinal symptoms occur.
3. Septicemia accounts for only about 5% to
10% of Salmonella infections and occurs
in one of two settings: a patient with an
underlying chronic disease such as sickle
cell anemia or cancer or a child with
enterocolitis.
• The epidemiology of Salmonella infections
is related to the ingestion of food and
water contaminated by human and animal
wastes. Sal. typhi, the cause of typhoid
fever, is transmitted only by humans, but
all other species have a significant animal
as well as human reservoir.
• Human sources are either persons who
temporarily excrete the organism during or
shortly after an attack of enterocolitis or
chronic carriers who excrete the organism
for years.
• The most frequent animal source is poultry
and eggs, but meat products that are
inadequately cooked have been implicated
as well.
Clinical Findings
• After an incubation period of 12 to 48
hours, enterocolitis begins with nausea and
vomiting and then progresses to abdominal
pain and diarrhea, which can vary from
mild to severe, with or without blood.
• Usually the disease lasts a few days, is self-
limited, causes nonbloody diarrhea, and
does not require medical care except in the
very young and very old.
• HIV-infected individuals, especially those
with a low CD4 count, have a much
greater number of Salmonella infections,
including more severe diarrhea and more
serious metastatic infections than those
who are not infected with HIV.
Treatment
• Enterocolitis caused by Salmonella is
usually a self-limited disease that resolves
without treatment.
• The treatment of choice for enteric fevers
such as typhoid fever and septicemia with
metastatic infection is either ceftriaxone or
ciprofloxacin.
• Ampicillin or ciprofloxacin should be used
in patients who are chronic carriers of Sal.
typhi.
Prevention
• Salmonella infections are prevented mainly
by public health and personal hygiene
measures.
• Proper sewage treatment, a chlorinated
water supply that is monitored for
contamination by coliform bacteria,
cultures of stool samples from food
handlers to detect carriers, handwashing
prior to food handling, pasteurization of
milk, and proper cooking of poultry, eggs,
and meat are all important.
 Shigella
Disease
• Shigella species cause enterocolitis.
Enterocolitis caused by Shigella is often
called bacillary dysentery. The term
"dysentery" refers to bloody diarrhea.
Important Properties
• Shigellae are non–lactose-fermenting,
gram-negative rods that can be
distinguished from salmonellae by three
criteria: they produce no gas from the
fermentation of glucose, they do not
produce H2S, and they are nonmotile.
Pathogenesis & Epidemiology
• Shigellae are the most effective pathogens
among the enteric bacteria
• Shigellosis is only a human disease, i.e.,
there is no animal reservoir. The organism
is transmitted by the fecal–oral route.
• The four Fs—fingers, flies, food, and
feces—are the principal factors in
transmission. Foodborne outbreaks
outnumber water-borne outbreaks by 2 to
1.
• Outbreaks occur in day care nurseries and
in mental hospitals, where fecal–oral
transmission is likely to occur.
• Shigellae, which cause disease almost
exclusively in the gastrointestinal tract,
produce bloody diarrhea (dysentery) by
invading the cells of the mucosa of the
distal ileum and colon.
• Although some strains produce an
enterotoxin (called Shiga toxin), invasion is
the critical factor in pathogenesis.
Clinical Findings
• After an incubation period of 1 to 4 days,
symptoms begin with fever and abdominal
cramps, followed by diarrhea, which may
be watery at first but later contains blood
and mucus.
• The disease varies from mild to severe
depending on two major factors: the
species of Shigella and the age of the
patient, with young children and elderly
people being the most severely affected.
Treatment
• The main treatment for shigellosis is fluid
and electrolyte replacement. In mild cases,
no antibiotics are indicated.
Prevention
• Prevention of shigellosis is dependent on
interruption of fecal–oral transmission by
proper sewage disposal, chlorination of
water, and personal hygiene (handwashing
by food handlers).
• There is no vaccine, and prophylactic
antibiotics are not recommended.
 Vibrio
Diseases
• Vibrio cholerae, the major pathogen in this
genus, is the cause of cholera. Vibrio
parahaemolyticus causes diarrhea
associated with eating raw or improperly
cooked seafood.
• Vibrios are curved, comma-shaped gram-
negative rods
Pathogenesis & Epidemiology
• V. cholerae is transmitted by fecal
contamination of water and food,
primarily from human sources. Human
carriers are frequently asymptomatic and
include individuals who are either in the
incubation period or convalescing.
• The pathogenesis of cholera is dependent
on colonization of the small intestine by
the organism and secretion of enterotoxin
• After adhering, the organism multiplies and
secretes an enterotoxin called choleragen.
• This exotoxin can reproduce the symptoms
of cholera even in the absence of the
Vibrio organisms.
• Morbidity and death are due to
dehydration and electrolyte imbalance.
However, if treatment is instituted
promptly, the disease runs a self-limited
course in up to 7 days.
Clinical Findings
• Watery diarrhea in large volumes is the
hallmark of cholera. There are no red
blood cells or white blood cells in the
stool.
• Rice-water stool is the term often applied
to the nonbloody effluent. There is no
abdominal pain, and subsequent symptoms
are referable to the marked dehydration.
Treatment
• Treatment consists of prompt, adequate
replacement of water and electrolytes,
either orally or intravenously.
• Antibiotics such as tetracycline are not
necessary, but they do shorten the duration
of symptoms and reduce the time of
excretion of the organisms.
Prevention
• Prevention is achieved mainly by public
health measures that ensure a clean water
and food supply.
• The vaccine, composed of killed organisms,
has limited usefulness; it is only 50%
effective in preventing disease for 3 to 6
months and does not interrupt
transmission.
 Campylobacter
Diseases
• C. jejuni is a frequent cause of enterocolitis,
especially in children.
• Other Campylobacter species are rare
causes of systemic infection, particularly
bacteremia.
• Campylobacters are curved, gram-negative
rods that appear either comma- or S-
shaped.
Pathogenesis & Epidemiology
• Domestic animals such as cattle, chickens,
and dogs serve as a source of the
organisms for humans.
• Transmission is usually fecal–oral. Food and
water contaminated with animal feces is
the major source of human infection.
• Foods, such as poultry, meat, and
unpasteurized milk, are commonly
involved.
Clinical Findings
• Enterocolitis, caused primarily by C. jejuni,
begins as watery, foul-smelling diarrhea
followed by bloody stools accompanied by
fever and severe abdominal pain.
• Systemic infections, most commonly
bacteremia, are caused by C. intestinalis.
• The symptoms of bacteremia, e.g., fever
and malaise, are associated with no specific
physical findings.
Treatment
• Erythromycin or ciprofloxacin is used
successfully in C. jejuni enterocolitis. The
treatment of choice for C. intestinalis
bacteremia is an aminoglycoside.
Prevention
• There is no vaccine or other specific
preventive measure. Proper sewage
disposal and personal hygiene
(handwashing) are important.
 Helicobacter
Diseases
• Helicobacter pylori causes gastritis and
peptic ulcers.
• Infection with H. pylori is a risk factor for
gastric carcinoma and is linked to mucosal-
associated lymphoid tissue (MALT)
lymphomas.
• Helicobacters are curved gram-negative
rods similar in appearance to
campylobacters
Pathogenesis & Epidemiology
• H. pylori attaches to the mucus-secreting
cells of the gastric mucosa. The production
of large amounts of ammonia from urea by
the organism's urease, coupled with an
inflammatory response, leads to damage to
the mucosa.
• Loss of the protective mucus coating
predisposes to gastritis and peptic ulcer.
• The natural habitat of H. pylori is the
human stomach, and it is probably
acquired by ingestion. However, it has not
been isolated from stool, food, water, or
animals.
• Person-to-person transmission probably
occurs because there is clustering of
infection within families.
• The rate of infection with H. pylori in
developing countries is very high—a
finding that is in accord with the high rate
of gastric carcinoma in those countries.
Clinical Findings
• Gastritis and peptic ulcer are characterized
by recurrent pain in the upper abdomen,
frequently accompanied by bleeding into
the gastrointestinal tract. No bacteremia or
disseminated disease occurs.
Treatment & Prevention
• The concept that underlies the choice of
drugs is to use antibiotics to eliminate
Helicobacter plus a drug to reduce gastric
acidity.
• Treatment of duodenal ulcers with
antibiotics, e.g., amoxicillin and
metronidazole results in a greatly
decreased recurrence rate.
• There is no vaccine or other specific
preventive measure.
 Klebsiella–Enterobacter–Serratia
Group
Diseases
• These organisms are usually opportunistic
pathogens that cause nosocomial
infections, especially pneumonia and
urinary tract infections.
• Klebsiella pneumoniae is an important
respiratory tract pathogen outside hospitals
as well.
Pathogenesis & Epidemiology
• Of the three organisms, K. pneumoniae is
most likely to be a primary, non-
opportunistic pathogen; this property is
related to its antiphagocytic capsule.
• Although this organism is a primary
pathogen, patients with K. pneumoniae
infections frequently have predisposing
conditions such as advanced age, chronic
respiratory disease, diabetes, or alcoholism.
• Enterobacter and Serratia infections are
clearly related to hospitalization, especially
to invasive procedures such as intravenous
catheterization, respiratory intubation, and
urinary tract manipulations.
• Serratia also causes endocarditis in users of
injection drugs.
• As with many other gram-negative rods,
the pathogenesis of septic shock caused by
these organisms is related to the
endotoxins in their cell walls.
Clinical Findings
• Urinary tract infections and pneumonia are
the usual clinical entities associated with
these three bacteria, but bacteremia and
secondary spread to other areas such as the
meninges and liver occur.
Treatment
• An aminoglycoside, e.g., gentamicin, and a
cephalosporin, e.g., cefotaxime, are used
empirically until the results of testing are
known.
Prevention
• Some hospital-acquired infections caused
by gram-negative rods can be prevented by
such general measures as changing the site
of intravenous catheters, removing urinary
catheters when they are no longer needed,
and taking proper care of respiratory
therapy devices.
• There is no vaccine.
 Pseudomonas
Diseases
• Pseudomonas aeruginosa causes infections
(e.g., sepsis, pneumonia, and urinary tract
infections) primarily in patients with
lowered host defenses.
Pathogenesis & Epidemiology
• Pse. aeruginosa is found chiefly in soil and
water, although approximately 10% of
people carry it in the normal flora of the
colon.
• It is found on the skin in moist areas and
can colonize the upper respiratory tract of
hospitalized patients.
• Pse. aeruginosa is primarily an
opportunistic pathogen that causes
infections in hospitalized patients
• Pathogenesis is based on multiple virulence
factors: endotoxin, exotoxins, and enzymes.
Its endotoxin, like that of other gram-
negative bacteria, causes the symptoms of
sepsis and septic shock.
• The best known of the exotoxins is exotoxin
A, which causes tissue necrosis.
Clinical Findings
• Pse. aeruginosa can cause infections virtually
anywhere in the body, but urinary tract
infections, pneumonia (especially in cystic
fibrosis patients), and wound infections
(especially burns) predominate.
Prevention
• Prevention of Pse. aeruginosa infections
involves removing indwelling catheters
promptly, taking special care of burned
skin, and taking other similar measures to
limit infection in patients with reduced
host defenses.