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Dr.T.V.Rao MD
ENTEROBACTER AN EMERGING NOSOCOMIAL PATHOGEN
DR.T.V.RAO MD 1
• Enterobacter is a genus of common
Gram-negative, facultatively-
anaerobic, rod-shaped bacteria
of the family Enterobacteriaceae.
Several strains of the these
bacteria are pathogenic and
cause opportunistic infections in
immunocompromised (usually
hospitalized) hosts and in those
who are on mechanical
ventilation. The urinary and
respiratory tract are the most
common sites of infection. It is
also a fecal coliform, along with
Escherichia.
ENTEROBACTER LEADING CAUSE OF
OPPORTUNISTIC INFECTIONS
DR.T.V.RAO MD 2
• Enterobacter is a gram-
negative bacillus that
belongs to the
Enterobacteriaceae family.
Other members of this
family include Klebsiella,
Escherichia, Citrobacter,
Serratia, Salmonella, and
Shigella species, among
many others.
ENTEROBACTER IS A
ENTEROBACTERIACEAE
DR.T.V.RAO MD 3
BACKGROUND OF ENTEROBACTER SPECIES
• Enterobacter species, particularly Enterobacter cloacae
and Enterobacter aerogenes, are important nosocomial
pathogens responsible for various infections, including
bacteremia, lower respiratory tract infections, skin and
soft-tissue infections, urinary tract infections (UTIs),
endocarditis, intra-abdominal infections, septic arthritis,
osteomyelitis, and ophthalmic infections. Enterobacter
species can also cause various community-acquired
infections, including UTIs, skin and soft-tissue
infections, and wound infections, among others
DR.T.V.RAO MD 4
OTHER SPECIES OF
ENTEROBACTER
• The most commonly isolated species include E cloacae and E aerogenes, followed by E sakazakii (recently reclassified into the Achromobacter genus, which produces a characteristic yellow pigment. Other species rarely encountered in the laboratory include Enterobacter asburiae, Enterobacter gergoviae, Enterobacter taylorae, Enterobacter hormaechei, and Enterobacter cancerogenus. Enterobacter agglomerans has been removed from the genus Enterobacter and renamed Pantoea agglomerans.
DR.T.V.RAO MD 5
• Enterobacter
aerogenes is a
Gram-negative,
oxidase negative,
catalase positive,
citrate positive,
indole negative, rod-
shaped bacterium.
ENTEROBACTER AEROGENES -
CHARACTERISTICS
DR.T.V.RAO MD 6
• E. aerogenes is part of
the flora found in the
human intestines. As an
opportunistic pathogen
it may infect immuno-
compromised patients
in the urinary and
respiratory tracts. It
rarely infects healthy
people
ENTEROBACTER AEROGENES IS PART OF
NORMAL FLORA CAN BE INFECTIVE …
DR.T.V.RAO MD 7
DR.T.V.RAO MD 8
• E. aerogenes is a nosocomial
and pathogenic bacterium that
causes opportunistic infections
including most types of
infections. Enterobacter species
can also cause various
community-acquired infections.
Some strains can become very
treatment resistant, a result of
their colonization within hospital
environments. However, the
majority are sensitive to most
antibiotics designed for this
bacteria class.
ENTEROBACTER AEROGENES IMPORTANT
NOSOCOMIAL PATHOGEN
DR.T.V.RAO MD 9
• Some of the infections caused by
E. aerogenes result from
specific antibiotic treatments,
venous catheter insertions,
and/or surgical procedures. E.
aerogenes is generally found in
the human gastrointestinal tract
and does not generally cause
disease in healthy individuals. It
has been found to live in various
wastes, hygienic chemicals, and
soil.
SOURCE OF ENTEROBACTER
INFECTIONS
DR.T.V.RAO MD 10
• Although community-acquired
Enterobacter infections are
occasionally reported,
nosocomial Enterobacter
infections are, by far, most
common. Patients most
susceptible to Enterobacter
infections are those who stay
in the hospital, especially the
ICU, for prolonged
periods
PROLONGED STAY IN HOSPITAL PREDISPOSES TO
ENTEROBACTER INFECTIONS
DR.T.V.RAO MD 11
• Other major risk factors of Enterobacter infection include prior use of antimicrobial agents, concomitant malignancy (especially hemopoietic and solid-organ malignancies), hepatobiliary disease, ulcers of the upper gastrointestinal tract, use of foreign devices such as intravenous catheters, and serious underlying conditions such as burns, mechanical ventilation, and immunosuppression.
OTHER PREDISPOSING FACTORS
DR.T.V.RAO MD 12
• The source of infection
may be endogenous
(via colonization of the
skin, gastrointestinal
tract, or urinary tract) or
exogenous, resulting
from the ubiquitous
nature of Enterobacter
species
ENDOGENOUS SOURCE –
MAJOR SOURCE OF INFECTION
DR.T.V.RAO MD 13
• These bacteria have an
outer membrane that
contains, among other
things, lipopolysaccharides
from which lipid-A plays a
major role in sepsis. Lipid-
A, also known as
endotoxin, is the major
stimulus for the release of
cytokines, which are the
mediators of systemic
inflammation and its
complications.
PATHOPHYSIOLOGY
DR.T.V.RAO MD 14
• Multiple reports have
incriminated the hands of
personnel, endoscopes, blood
products, devices for monitoring
intra-arterial pressure, and
stethoscopes as sources of
infection. Outbreaks have been
traced to various common
sources: total parenteral nutrition
solutions, isotonic saline
solutions, albumin, digital
thermometers, and dialysis
equipment.
IMPORTANT OTHER SOURCES
DR.T.V.RAO MD 15
• Enterobacter species contain a
subpopulation of organisms that
produce a beta-lactamase at
low-levels. Once exposed to
broad-spectrum cephalosporins,
the subpopulation of beta-
lactamase–producing organisms
predominate. Thus, an
Enterobacter infection that
appears sensitive to
cephalosporins at diagnosis may
quickly develop into a resistant
infection during therapy
ENTEROBACTER PRODUCE BETA
LACTAMASES
DR.T.V.RAO MD 16
• The most important test to
document Enterobacter
infections is culture. Direct
Gram staining of the
specimen is also very
useful because it allows
rapid diagnosis of an
infection caused by gram-
negative bacilli and helps in
the selection of antibiotics
with known activity against
most of these bacteria
MICROBIOLOGICAL STUDIES
DR.T.V.RAO MD 17
• In the laboratory,
growth of Enterobacter
isolates is expected to
be detectable in 24
hours or less.
Enterobacter species
grow rapidly on
selective (ie,
MacConkey) and
nonselective (ie,
sheep blood) agars.
CAN BE ISOLATED ON COMMONLY USED
MEDIA
DR.T.V.RAO MD 18
MICROSCOPY AND CULTURING HELPS IN
DIAGNOSIS
DR.T.V.RAO MD 19
• Grown on eosin
methylene blue
(EMB) agar. EMB
agar contains the
indicator dyes
eosin and
methylene blue.
AS GROWN ON EOSIN METHYLENE BLUE
MEDIUM
DR.T.V.RAO MD 20
• Oxoid has introduced
Oxoid Chromogenic
Enterobacter sakazakii
Agar (Druggan-
Forsythe-Iversen (DFI)
formulation) that allows
recovery and detection
of E. sakazakii in just 3
days – 2 days faster
than by conventional
methods
FASTER DETECTION WITH OXOID CHROMOGENIC
ENTEROBACTER SAKAZAKII AGAR (DRUGGAN-FORSYTHE-
IVERSEN (DFI) FORMULATION
DR.T.V.RAO MD 21
• This innovative new
chromogenic medium
contains the substrate 5-
bromo-4-chloro-3-indolyl-α,
D-glucopyranoside which is
cleaved by the enzyme α-
glucosidase, expressed by
E. sakazakii, to form easily
distinguishable blue-green
colonies.
OXOID CHROMOGENIC ENTEROBACTER
SAKAZAKII AGAR
DR.T.V.RAO MD 22
• Merck's new ChromoCult® Enterobacter sakazakii Agar will increase the security in detecting this microorganism in milk powder and infant formula.
• Based on the alpha-D-Glucosidase - an enzyme specific for E. sakazakii - only the colonies of E. sakazakii appear turquoise while other bacteria grow colourless. ChromoCult® Enterobacter sakazakii Agar allows a fast and reliable detection within only 24 hours with no further confirmation step.
MERCK'S NEW CHROMOGENIC MEDIUM FOR
DETECTION OF ENTEROBACTER SAKAZAKII
DR.T.V.RAO MD 23
• Two sets (with one aerobic and
one anaerobic bottle in each set)
should be obtained 20-30
minutes apart, from 2 different
sites (if possible). If the patient
has a central venous catheter,
one set should be drawn through
it. In the adult patient, 8-10 mL of
blood should be collected in each
bottle. Enterobacteriaceae
ferment glucose and should thus
grow in both bottles.
BLOOD CULTURE FOR IDENTIFICATION
DR.T.V.RAO MD 24
• Penicillin's should include
ampicillin and at least one
of the extended-spectrum
penicillin's (eg, carboxy,
ureido, or
acylaminopenicillin) such
as ticarcillin, mezlocillin, or
piperacillin. The addition of
ticarcillin-clavulanic acid or
piperacillin-tazobactam is
optional.
DRUGS TO INCLUDE FOR ANTIMICROBIAL
SUSCEPTIBILITY TESTING
DR.T.V.RAO MD 25
CHOOSING A RIGHT ANTIBIOTIC
• Cephalosporins include a first-generation drug of this class of
antibiotics, such as cefazolin, and a third-generation drug with
and without Pseudomonas activity, such as ceftriaxone or
ceftazidime.
Include at least one carbapenem, usually imipenem, or in
accordance with available pharmaceutical agents in the
institution.Include the aminoglycosides, usually gentamicin and
tobramycin.
Amikacin may be tested primarily or when bacteria show
resistance to these 2 drugs. Include a quinolone, such as
ciprofloxacin.Include TMP-SMZ.Some laboratories routinely add
aztreonam.
DR.T.V.RAO MD 26
EMERGING GENETIC MECHANISMS OF
RESISTANCE
• Recently, the production of extended-spectrum beta-lactamases (ESBLs) has been documented in Enterobacter. Usually, these ESBLs are TEM1 -derived or SHV1 -derived enzymes, and they have been reported since 1983 in Klebsiella pneumoniae, Klebsiella oxytoca, and E coli. Bush et al classify these ESBLs in group 2be and in molecular class A in their beta-lactamase classification. The location of these enzymes on plasmids favors their transfer between bacteria of the same and of different genera. Many other gram-negative bacilli may also possess such resistant plasmids
DR.T.V.RAO MD 27
DR.T.V.RAO MD 28
• Hyper production (stable DE
repression) of AmpC beta-
lactamases associated with
some decrease in permeability to
the carbapenems may also
cause resistance to these
agents. In vitro low-level
ertapenem resistance was not
associated with resistance to
imipenem or meropenem, but
high-level ertapenem resistance
predicted resistance to the other
carbapenems
CARBAPENEMS TOO ARE BECOMING
RESISTANT
DR.T.V.RAO MD 29
• Colistin and polymyxin B: These
drugs are being used more
frequently to treat serious
infection caused by multidrug-
resistant organisms, sometimes
as monotherapy or in
combination with other
antibiotics. Clinical experience,
including documentation of
success rates and attributable
mortality is broadening
COLISTIN AND POLYMYXIN B ARE GAINING
IMPORTANCE IN TREATMENTS
DR.T.V.RAO MD 30
• The fourth-generation
cephalosporins are
relatively stable to the
action of AmpC beta-
lactamases; consequently,
they retain moderate
activity against the mutant
strains of Enterobacter,
hyper producing AmpC
beta-lactamase
4 TH GENERATION CEPHALOSPORINS ARE A
CHOICE
DR.T.V.RAO MD 31
• Other antibiotics that
may be considered
for testing include
tigecycline,
polymyxin B, and
colistin, the latter two
when particularly
resistant organisms
are identified
OTHER NEW GENERATION OF ANTIBIOTICS
DR.T.V.RAO MD 32
• Enterobacter sakazakii has been reported as a cause of
sepsis and meningitis,
complicated by ventriculitis, brain
abscess, cerebral infarction, and
cyst formation.[ This clinical
pattern appears to be specific to
E sakazakii in neonates and
infants infected with this
bacterium. E sakazakii has also
been associated with many
outbreaks due to contaminated
powdered formula for infants
• Enterobacter sakazakii
ENTEROBACTER SAKAZAKII
A IMPORTANT SPECIES
DR.T.V.RAO MD 33
• The bacteria designated by the acronym
SERMOR-PROVENF (SER = Serratia,
MOR = Morganella, PROV = Providencia,
EN = Enterobacter, F = freundii for
Citrobacter freundii) have similar,
although not identical, chromosomal
beta-lactamase genes that are inducible.
With Enterobacter, the expression of the
gene AmpC is repressed, but
derepression can be induced by beta-
lactams. Of these inducible bacteria,
mutants with constitutive hyperproduction
of beta-lactamases can emerge at a rate
between 105 and 108. These mutants are
highly resistant to most beta-lactam
antibiotics and are considered stably
derepressed.
SERMOR-PROVENF
DR.T.V.RAO MD 34
• The National Healthcare
Safety Network (NHSN)
reported on healthcare-
associated infections (HAI)
between 2006 and 2007.
They found Enterobacter
species to be the eighth
most common cause of HAI
(5% of all infections) and
the fourth most common
gram-negative cause of
HAIs.[
THE NATIONAL HEALTHCARE SAFETY NETWORK
(NHSN) REPORTS ON ENTEROBACTER
DR.T.V.RAO MD 35
HAND WASHING STILL REDUCES SPREAD OF
ENTEROBACTER IN THE HOSPITAL ENVIRONMENT
DR.T.V.RAO MD 36
DR.T.V.RAO MD 37
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DR.T.V.RAO MD 38