Infection, Biofilm,

Hospital Infection
TITIEK DJANNATUN
FAKULTAS KEDOKTERAN UNIVERSITAS YARSI
 some of the terms that must be understood
• Adherence (adhesion, • Opportunistic pathogen
attachment) • Pathogen
• Carrier • Pathogenicity
• Infection • Toxigenicity
• Invasion • Virulence
• Nonpathogen
Introduction
• Infection is multiplication of an infectious agent within the body 
multiplication of pathogenic bacteria (eg. Salmonella enteritica), event if the
person is asymptomatic  how about normal flora?
• The causes of infectious diseases  Koch’s postulates
• The application of principles such as Koch’s postulates leads to classification of
bacteria as :
• pathogens  their presence is abnormal (Mycobacterium tuberculosis)
• opportunistic pathogens  cause disease in immunosuppressed and debilated persons
• nonpathogens  normal flora in human and animals
 Microcolonies

Infection is the
lodgement and
multiplication of
Biofilms of the different organism in the
types of bacteria tissue of host
 Classification of infections
1. Primary infection: Initial infection with organism in host.
2. Reinfection: Subsequent infection by same organism in a host (after recovery).
3. Superinfection: Infection by same organism in a host before recovery.
4. Secondary infection: When in a host whose resistance is lowered by preexisting infectious disease, a
new organism may set up in infection.
5. Focal infection: It is a condition where due to infection at localized sites like appendix and tonsil,
general effects are produced.
6. Cross infection: When a patient suffering from a disease and new infection it set up from another host
or external source.
7. Nosocomial infection: Cross infection occurring in hospital.
8. Subclinical infection: It is one where clinical affects are not apparent.
Causative agents of infections
Saprophytes: They are free living organisms which fail to
multiply on living tissue and so are not important in infectious
disease.
Parasites: They are organisms that can establish themselves and
multiply in hosts. They may be pathogens or commensal.
Pathogens are those which are capable of producing disease in a
host. On the contrary commensal microbes can live in a host
without causing any disease.
Sources of infection in Man
Man: Man is himself a common source of infection from a patient or carrier. Healthy carrier is a
person harboring pathogenic organism without causing any disease to him. A
convalescent carrier is one who has recovered from disease but continues to harbor the
pathogen in his body  Anthroponosis
Animals: Infectious diseases transmitted from animals to man are called zoonosis. Zoonosis
may be bacterial, (e.g. Plague from rat), rickettsial, (e.g. Murine typhus from rodent), viral, (e.g.
Rabies from dog), protozoal, (e.g. Leishmaniasis from dogs), helminthic, (e.g. Hydatid cyst from
dogs) and fungal (zoophilic dermatophytes from cats and dogs).
Insects: The diseases caused by insects are called arthropod borne disease. Insects like
mosquitoes, fleas, lice that transmit infection are called vector. Transmission may be
mechanical (transmission of Dysentery or typhoid bacilli by housefly) and these are called
mechanical vector. They are called biological vector if pathogen multiplies in the body of
vector, e.g. Anopheles mosquito in Malaria.
Sources of infection in Man
Some vectors may acts as reservoir host, (e.g. ticks in
Relapsing fever and Spotted fever).
Soil: Spores of tetanus bacilli, Gas-gangrene infection
remain viable in soil for a long time.

Clostridium tetani
Sources of infection in Man
Water: Vibrio cholerae, infective hepatitis virus (Hepatitis A and
Hepatitis E) may be found water.
Food: Contaminated food may be source of infection. Presence of
pathogens in food may be due to external contamination, (e.g.
food poisoning by Staphylococcus).
 Entry into the human body

The most frequent portals of

entry are the sites where
mucous membranes meet with
the skin. Abnormal areas of
mucous membranes and skin
are also frequent sites of entry.

Routes:
Ingestion, inhalation, trauma,
needles, catheters, arthropod
bite, sexual transmission
: infection : shedding
Methods of Transmission of Infection
• Contact (sexual intercourse): syphilis, gonorrhea.
• Inhalation/airborne droplets: influenza, tuberculosis, smallpox, measles,
mumps, HFMD.
• Ingestion: cholera (water), food poisoning (food) and dysentery (hand borne).
• Inoculation: tetanus (infection), rabies (dog), arbovirus (insect) and serum
hepatitis, i.e. Hepatitis B (infection).
• Congenital: syphilis, rubella, toxoplasmosis, cytomegaloviruses
• Insects: they act as mechanical vector (dysentery and typhoid by housefly) or
biological vector (malaria) of infectious disease
Inhalation/airborne
droplets

Congenital

Insects
Characters of pathogens
• Bacteria should be able to enter the body  Portal of entry
• Organism should be able to multiply in the tissue  dose of
infection, host immunity
• They should be able to damage the tissue  adhesin factor,
afinitas jaringan, virulence factor, pathogenicity
• They must be capable to resist the host defense virulence
factor, pathogenicity
Characteristics of Pathogenic Bacteria
1. Transmissibility
2. Adherence to host cells
3. Invasion of host cells and tissue
4. Evasion of the host immune system
5. Toxigenicity

A bacterium may cause diseases by

1. Destroying tissue (invasiveness)
2. Producing toxins (toxigenicity)
3. Stimulating overwhelming host immune responses
Bacterial Virulence Mechanisms
 Bacterial virulence factors
Adhesins Antiphagocytic factors
Pili (fimbriae) Intracellular survival
Nonfimbrial adhesins Antigenic heterogeneity
Invasion of host cells Antigenic variation
Tissue damage Phase variation

Growth byproducts
Tissue-degrading enzymes
Immunopathogenesis Iron acquisition
Toxins Siderophores
Receptors for
Exotoxins (cytolytic enzymes and
A-B toxins); enterotoxins; iron-containing molecules

superantigens; Resistance to antibiotics

endotoxin and other cell wall

components
Mechanisms of acquiring bacterial virulence genes
 Virulence factor
• Adhesin  The attachment of the bacteria to body surfaces
• Invasiveness  hyaluronidase, fibrinolysin
• Toxigenicity
• communicability
• Coagulase
• Leucocidin, hemolysin, IgA1 proteases, protein A
Microbial defenses against host immunologic clearance
Encapsulation (Inhibition of phagocytosis and serum bactericidal
effect)
Antigenic mimicry
Antigenic masking
Antigenic or phase variation
Intracellular multiplication
Escape phagosome
Inhibition of phagolysosome fusion
Resistance to lysosomal enzymes
Production of anti-immunoglobulin protease
Inhibition of chemotaxis
Destruction of phagocytes
Mechanisms for escaping
phagocytic clearance and
intracellular survival
Mechanisms for escaping
phagocytic clearance and
intracellular survival
Mechanisms for escaping
phagocytic clearance and
intracellular survival
 Endotoxin-mediated toxicity
Fever,
leukopenia followed by leukocytosis,
activation of complement, thrombocytopenia,
disseminated intravasacular coagulation,
decreased peripheral circulation and perfusion to
major organs (multiple organ system failure),
Shock and death.
Peptidoglycan, teichoic and lipoteichoic acids of gram-
positive bacteria stimulate pyrogenic acute phase
responses and produce endotoxin-like toxicity

Back
Lipid A of lipopolysaccharide
is responsible for endotoxin
activity

Pathogenesis of
sepsis (septicemia)
 Types of infectious diseases
• Infectious diseases may be localized or generalized. Localized infections may be superficial or deep-seated.
• Circulation of bacteria in the blood is known as bacteremia (viruses – virusemia).
• Septicemia is the condition where bacteria circulate and multiply in the blood, form toxic products and cause
swinging type of fever.
• Pyemia is a condition where pyogenic bacteria produce septicemia with multiple abecesses in the internal organs
such as the spleen, liver, and kidney
• Depending on the spread of infectious disease in the community they may be classified into different types.
• Endemic disease
• Epidemic
• Pandemic
• Epidemics
 Stages of infectious disease
Incubation period – no symptoms.
Prodromal period – mild and generalized symptoms
(fever, weakness, headache).
Invasive stage – symptoms specific to the disease.
Decline stage – symptoms subside.
Convalescence – no symptoms, health returns to normal.
 Biofilms
Biofilms form when bacteria adhere to surfaces in aqueous environments
and begin to excrete a slimy, glue-like substance that can anchor them to
all kinds of material (metals, plastics, medical implant materials and,
human or animal tissue).

Hundreds of microbial biofilm colonize the human mouth, causing tooth decay and gum disease.
 Quorum Sensing
Many groups of bacteria can communicate - by releasing and detecting chemical
pheromones to gauge their population density - the molecular structure of a key
protein in this interbacterial communication has been solved.
Quorum sensing provides an explanation for why some disease-causing virulence
factors are not expressed during the early stages of encounter with the human host
 Characteristics of biofilm
A biofilm can contain a single species of bacteria or several
species.
Genetic studies confirm that bacteria switch on different
genes, depending on whether they're living as free-floating
microbes or clustering as biofilms.
Biofilm bacteria can be up to 1000 times more resistant to
antimicrobial stress (e.g. antibiotics and disinfectants) than
free-swimming bacteria of the same species.
Plaque is a biofilm on the surfaces of the teeth which secretes acids that destroy
teeth and gumsz

Dental plaque as seen

under a scanning electron
microcroscope
5 stages of P.aeruginosa biofilm
development
1. initial attachment
2. irreversible attachment;
3. 4 - maturation
5. dispersion.
Hospital Infection
Introduction
 Definition  Infection associated with healthcare settings. The incubation periode during
hospitalization
 Hospital infection/Nosocomial infection may be aqquired from:
 An exogenous source  from another patient – cross infection – or from the environtment
 An endogenous source  another site within patient – self – or auto infection
 Common hospital infection:
 Urinary tract infection  E. coli, enterococci, staphylococci, candida
 Surgical wound infection  S. aureus (staphylococci coagulase negative), enterococci, E. coli,
P. aeruginosa
 Lower respiratory tract infection  S. aureus, P. aeruginosa
 Bacteremia  S. aureus (staphylococci coagulase negative), enterococci, candida, E. coli
Hospital-acquired infection (Goering et al., 2008)
Consecquences of Hospital infection
 Serious illness or death
 Prolonged hospital stay  cost money
 a need for additional antimicrobial therapy  costly, risk of
toxicity, increases selective pressure for resistance to emerge among
hospital pathogens
 the infected patient becoming a source from which others may
become infected, in hospital and in the community
Prevention of hospital infection
excluding sources of infection from the hospital
environment
 Interrupting the transmission infection from source to
susceptible host (breaking the chain of infection)  control
of air-borne transmission, facilitation of aseptic behavior
 enhancing the host’s ability to resist infection