PATHOGENESIS OF BACTERIAL

INFECTION &
NOSOCOMIAL INFECTION

Introduction

Infection identification of microorganisms in host

tissue or the blood stream, plus an inflamatory

response to their presence (Schwartzs)
Infection invasion of the host by microorganisms,

which then multiply in close association with the host's

tissues.
Bacteria can cause a multitude of different infections,

ranging in severity from inapparent to fulminating

Pathogenesis

Pathogenesis refers both to the mechanism of

infection and to the mechanism by which disease

develops

Pathogenesis : The development of morbid conditions

or of disease; more specifically the cellular events

and reactions and other pathologic mechanisms
occurring in the development of disease (dorland)

Many bacterial virulence factors and, where

possible, to indicate how they interact with host

defense mechanisms and to describe their role in
the pathogenesis of disease

Multi-factorial process

depends on:

1.the immune status of the host,

2.the nature of the species or strain (virulence

factors) and
3.the number of organisms in the initial
exposure.

* Why/when does disease occur?

- pathogen causes loss of function or
death
of a significant number of host cells
* Outcome depends on balance between
host defense
and cell destruction caused by
pathogen

Mechanisms for producing

disease
Disease define as damage to host

Invading and multiplying within host

Producing toxins that impair host
Both

A limited number of bacterial species are

responsible for the majority of infectious

diseases in healthy individuals.
Due to the success of vaccination, antibiotics,
and effective public health measures, until
recently, epidemics were felt to be a thing of
the past.
Due to the development of antibiotic
resistant organisms, this situation is changing
rapidly.

All humans are infected with bacteria (the

normal flora) living on their external surfaces

(including the skin, gut and lungs).
We are constantly also exposed to bacteria
(including air, water, soil and food).
Normally due to our host defenses most of
these bacteria are harmless.

In compromised patients, whose defenses are

weakened, these bacteria often cause

opportunistic infectious diseases when
entering the bloodstream (after surgery,
catheterization or other treatment modalities).

In the hospital,

nosocomial.

Some common bacteria found in the normal

flora include Staphylococcus aureus, S.

epidermidis and Propionibacterium acnes
(found on the skin) and Bacteroides and
Enterobacteriaceae found in the intestine (the
latter in much smaller numbers).

At the site of infection : inflammation

Rubor, calor and dolor (tumor and loss of

function)
Systemic manifestation :

Fever, leucocytosis, tachycardia,

tachypnea

Cardinal Signs of
Inflammation

Calor

Rubor

Tumor

Dolor Loss of Function

described by Celsus more than 2000 years ago.

Transmission
Contact most common
Direct (physical contact)
Indirect (via contaminated objects)

Airborne Transmission
Droplet respiratory secretions on surfaces
Inhalation of infectious particles

Blood-borne transmission
Food-borne

Host Defenses
Prevent invasion
Limit proliferation
Contain or eradicate

Factors that lowers Host Defences

Immunosuppressants
Chronic illness
Burns

Hosts Barriers (Nonspecific Immunity)

Epithelial (skin)
Mucosal (respiratory, gut and urogenital)
Secreted substances (sweat, tears, saliva,

sebaceous, wax, ect)

Resident or commensal microbes
Skin
Epithelial surface
Secretion from sebaceous gland
Resident microflora (gram (+))
Staphylococci,

streptococci, corynebacterium,
propionobacterium

Respiratory tract
Respiratory mucus coughing / swallowing
Pulmonary alveolar macrophages

phagocytosis
Normal flora :
Gram (+) : staphylococcus aureus,
streptococcus pneumopniae
Gram (-) : moraxella catarhalis,
haemophilus, neisseria
Urogenital, Billiary, Pancreatic ductal and

distal respiratory tract DO NOT posses

resident microflora in healthy individuals

Gastrointestinal (oropharynx, distal

colorectum) significant number of microbes

Smal intestine :
Gram (+) : lactobacillus, clostridium,
enterococci, staphylococcus
Gram (-) : enterobactericeae, bacteroides,
prevotella
Large intestine :
Gram (+) : lactobacillus, clostridium,
enterococci, peptostreptococcus,
streptococci, staphylococci, actinomyces
Gram (-) : enterobacteriaceae,
pseudomonas, acinetobacter, alcaligenes,
flavobacter, bacteroides, prevetolla,
fusobacterium

The Underlying Mechanisms of Bacterial

Pathogenicity

Two broad qualities of pathogenic bacteria

underlie the means by which they cause

disease:

- Invasiveness
- Toxigenesis

Invasiveness
The ability to invade tissues
Mechanisms for colonization (adherence

and initial multiplication),

Production of extra cellular substances
which facilitate invasion (invasins) and
Ability to bypass or overcome host
defense mechanisms/EVASION OF HOST
DEFENSES

COLONIZATION
The first stage of microbial infection

bacterial adherence or attachment to a eucaryotic

cell or tissue surface requires the participation of

two factors: a receptor and an ligand (adhesin)

Bacteria may need to have spesific

mechanism. so that they can adhere to and

colonize many different body surfaces
E.coli & other bacteria have adhesins that

bind to spesific receptors on the tissue

surface and this keeps them from being
washed away.
Many of these adhesins proteins are present

at the tips of fimbriae (pili) and bind tightly

to spesific sugars on the target tissue.

Toxigenesis
The ability to produce toxins
exotoxins : a potent toxin form and excreted by

the bacterial cell, and free in surrounding

medium.
Endotoxins : refers to the lipopolysaccharide
component of the outer membrane of Gramnegative bacteria).

Endotoxin & other cell wall

components
These components activate host protective

responses.
On infection with gram (+) bacteria
peptidoglycan and its breakdown products, as well
as teichoic and lipoteichoic acids, are released
,stimulate toxin like pyrogenic responses.
The LPS produced by gram (-) bacteria is an even
more powerful activator of inflamm.reactions, and
its presence is like a multi alarm warning to the
body to activate the hosts protective systems
The lipid A portion of LPS is responsible for
endotoxin activity.
Its is important to appreaciate that endotoxin is not the same as
exotoxin & that only gram(-) bact can produce endotoxin

Exotoxins
Are protein produced by gram (+) or gram (-)

bacteria and include cytolitic enzymes and

dimeric toxins with A and B subunits.
In many cases the toxin gene is encoded on
plasmid (tetanus toxin of C.tetani, LT and ST
toxinsof enterogenic E.coli) or a lysogenic phage
(Corynebacterium diphtheriae and C.botulinum).
Cytolitic toxin alpha toxin (phospolipase C)
produced by C.prefringens which
enzymatically attacks sphingomyelin and other
membrane phospolpids cell lysis.

Exotoxins
The B portion of the A-B toxins that constitute

the diameric toxins binds to a spesific cell

surface receptor, and then the A subunit is
transferres into the interior of the cell, where
cell injury is induced.
The tissues targeted by these toxins are very
defined and limited

SUPERANTIGENS
Special group of toxins
Toxin like molecules activate T cells by binding
to both the T cell receptor and also MCHC II on
another cell without requiring antigen
This nonspesific means activating T cells can
trigger life-threatening auto-imune like
responses by stimulating the release of large
amounts of IL.
Superantigen include the toxic syndrome toxin of
S.aureus, staphylococcal enterotoxins ant the
erythrogenic toxin A or C of S.pyogenes

Mechanisms for escaping host

defenses
Bacteria have developed ways to avoid being

recogized and killed by phagocytic cells and to

inactivate or evade the complement system
and antibody, and some bateria can hide fro
immune responses by growing intracelluarly.
The capsule is one of the most important
virulance factors.
these slime layers function by shielding the

bacteria from immune and phagocytic responses.

Usually made of hyaluronic acid
Also acts like a slimy football jersey

Bacteria can circumvent phagocytic killing in variety of

ways.
The can produce enzymes capable of lysing phagocytic

cells
They can inhibit phagocytosis or block intraceluller killing

Bacteria have also developed mechanisms to protect

them from intraceluller killing.

Ability to prevent phagolysosome fusion
Ability to resist beling kiled by bactericidal lysosomal

enzymes/substances.
Ability to exit the phagosome into the host cytoplasma
before being exposed to lysosomal enzymes.

Other important host defenses subverted by

bacteria include the alternate pathway of

complement & antibody
Bacteria evade complement action by masking

themselves and by inhibiting activation of the

cascade
The long O antigen of LPS reents complement
from ganing acess to the membrane and
protects gram (-) bacteria from damage

Etiology & Definition

Definition

Nosocomial infection defined as infections that

occur in a patient in a hospital or other
healtcare facility.
Etiology
Various pathogenic agent cause nosocomial

infections, patterns of agent vary greatly by the

site of infection.
Most common isolate is Escherichia coli.

Nosocomial infections
are
Infections that are
acquired in hospital
(48 hours or more after
admission)
Approx 10% of
patients will suffer
from an infection
whilst in hospital risk
increases with length
of stay

Problem oriented
Nosocomial
Infections.

The great problem:

Nosocomial pathogens are resistant to

antimicrobics

Variety of nosocomial
infection

SSIs (Surgical Site Infection)

Infections of the tissues, organs or spaces

exposed by surgeuons during invasive procedures

UTIs (Urinary Tract Infection)
Prolonged use of foley catheters
Culture results : > 104 CFU/mL of microbes
Pneumonia
Prolonged use of ventilation tubes
Bacteremic episodes
Prolonged use of venous or arterial access

Nosocomial infections
Bloodstream infections, 28%
Ventilator-associated pneumonia, 21%
Urinary tract infection (UTI), 15%
Lower respiratory infection, 12%
Gastrointestinal, skin, soft tissue, and

cardiovascular infections, 10%

Surgical-site infections, 7%
Ear, nose, and throat infections 7%

Surgical site infections

S aureus, 20%
Pseudomonads, 16%
Coagulase-negative staphylococci, 15%
Enterococci, fungi, Enterobacter species, and

Escherichia coli, less than 10% each

Urinary Tract Infections

Gram-negative enterics, 50%
Fungi, 25%
Enterococci, 10%

Bloodstream nosocomial
infections
Coagulase-negative staphylococci, 40%
Enterococci, 11.2%
Fungi, 9.65%
Staphylococcus aureus, 9.3%
Enterobacter species, 6.2%
Pseudomonads, 4.9%
Acinetobacter baumannii with substantial

antimicrobial resistance - Reported with

increasing frequency

Nosocomial infection

host

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microbes

environment

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Treatment

The Host
People in hospital are already sick!
They may have poor general resistance to infection
Lack of immunity
Extremes of age
Immunocompromised (eg HIV+, cancer chemotherapy)

Reduced immunity
Diabetes, severe burns

Poor local resistance

Poor blood supply to tissues

Surgery
Wounds, sutures

Medical devices
Catheters, prostheses, tubing etc

The microbes
Virtually any infection can be acquired in

hospital
However a number of usual suspects
predominate
What are they, where do they come from and
why do they cause nosocomial infection?

Opportunistic infections
Nosocomial

infections are often caused by

opportunistic pathogens i.e. those which do
not normally cause infection in healthy people

May be a reflection of reduced defences of host

or access to sites not normally colonised by

organisms

May be from normal flora or environment

Antibiotic resistance is a problem

Opportunistic pathogens
Pseudomonas aeruginosa
staphylococci
E. coli and other coliforms
streptococci and enterococci
Bacteroides fragilis
Candida albicans
Herpes simplex virus
Cytomegalovirus

Biofilms
Biofilms are microbial

communities (cities)
living attached to a solid
support eg catheters/
other medical devices
Biofilms are involved in
up to 60% of nosocomial
infections
Antibiotics are less
effective at killing
bacteria when part of a
biofilm

The Environment
There are many different sources of

pathogens when in hospital

Own normal flora (endogenous)
Infected patients
Traffic of staff and visitors
Environment e.g fungi, Legionella
Blood products
Surgical instruments eg vCJD

Treatment
There is continuous usage of antibiotics in

hospitals especially in ICU

As a result there will be a natural selection for
strains that are antibiotic resistant
This has led to problems with multi-resistant
bacteria e.g. MRSA, VRE, ESBLs
Antibiotic treatment can also lead to
alterations in normal flora and allow
pathogens cause infection eg C. difficile

Causes of death
1. Pneumonia
2. Infection of surgical site
3. Primary bloodstream infection

Infection Control
Infections may derive

from endogenous
(auto-infection) or
exogenous sources
(cross-infection)

We need to consider

the chain of infection

and the transmission
of an infectious agent

Decontamination of environment

Hand washing

Prudent use of antibiotics

Decontamination of equipment

Isolation & barrier precautions

THANK YOU..