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