3. Chemotherapeutic agent
Antimicrobial agents of synthetic origin
that can kill or inhibit the growth and
multiplication of microorganisms and
suitable for systemic use (chemically
synthesized
4. The antibiotic :
is a type of antimicrobial substance produced by a living
microorganism and is effective against another living
microorganism. Since ,several of these antibiotics are now
chemically synthesized, the term antibiotic is generally
used.
5. Broad spectrum antibiotics are effective antimicrobial
that affect wide variety of bacteria (both Gram- positive
and Gram-negative organisms).
6. Bacteriostatic : A chemotherapeutic
agent that affects bacteria by
inhibiting their growth and
multiplication.
Bactericidal: A chemotherapeutic
agent that affects bacteria by killing
them.
7. Selective toxicity:-
For an antimicrobial to be suitable for systemic use, it
should be harmful to the organism in a therapeutic doses
and not harmful to the host.
i.e. :The antimicrobial should act on specific receptor site on
the organism or inhibit a metabolic pathway essential for
the growth of the organism.
8. The mechanisms of action of antimicrobial agents
1- Inhibition of cell wall synthesis:
E.g. penicillin, cephalosporin, cycloserine and vancomycin. These
drugs inhibit the synthesis of peptidoglycan(the rigid envelope
which is found only in cell wall of bacteria) .Since the internal
osmotic pressure of the bacteria is high, they will take up fluid
rapidly and explode(cell death ensues).
Mycoplasma & L-form bacteria are resistant to these drugs.
9. 2-Interference with cell membrane function :
E.g. Amphotericin B, Polymyxins
,Colistin(polymixin E) ,imidazoles , these
drugs disrupt the functional integrity of
cytoplasmic membrane ,as a result
macromolecules and ions escape from
the cell and cell damage and death
ensues.
10. 3-Inhibition of protein synthesis:
Bacteria have70s (ribosomes sedimentation constant),
whereas mammalian cells have 80s ribosomes, the
subunits of each type of ribosome is different ,e.g.
aminoglycosides including streptomycin ,gentamycin
ect… ,act on 30s subunits, while lincomycins act on the
50s subunits of the microbial ribosome . Other e.g.,of
drugs that inhibit protein synthesis ,Chloramphenicol ,
erythromycin , tetracycline & aminoglycosides
11. 4- Inhibition of nucleic acid synthesis:
Quinolones , Refampicin and Metronidazole
These antimicrobials can act on any of the steps of DNA or
RNA replication (synthesis) Quinolones inhibit DNA
synthesis by blocking DNA gyrase ,an enzyme needed for
replication of bacterial chromosome Rifampicin inhibit
RNA synthesis by binding to DNA dependant RNA
polymerases.
12. Metronidazole:
Active against anaerobic bacteria and some
protozoa. Sensitive bacteria to this
antibiotic ,metabolize it to a compound that
bind to DNA prevent its replication and
rapidly kill the bacterial cell.
13. 5- Competitive Antagonism :
E.g. Sulphonamides & Trimethoprim are structural analogues to
PABA (the essential metabolite of folic acid) which is the
precursor for the synthesis of nucleic acid in bacterial cell. .
Sulphonamides compete with P-amino benzoic acid. They enter
into reaction in place of PABA and compete for the active center
of the enzyme. As a result, nonfunctional analogues of folic acid
are formed, and bacterial nucleic acid synthesis is inhibited .
14. COMPLICATION OF CHEMOTHERAPY
(1 ) Toxicity:
a-Tetracycline: if given to pregnant women (hepato-toxic for
mother) , and cause permanent discoloration (yellow or brown
staining of the teeth in fetus) .
b-Streptomycin is toxic to vestibular portion of eighth cranial nerve
causing tinnitus & vertigo, deafness .
c-Amino glycosides are nephrotoxic ,
d-Chloramphinicol causes bone marrow depression.
15. (2) Allergy :
Penicillin can cause allergic reaction which varies
from simple urticaria to anaphylactic shock.
Sulphonamides :
Topical application of sulphonamides may result in
contact dermatitis
16. (3) Drug resistance:
Due to abuse of antibiotics (no actual indication
,improper choice ,low dosage , interrupted course
that encourage the emergence of resistant
mutants of microorganisms. These mutants will
overgrow and replace the originally susceptible
population.
It is recommended to do in vitro culture and
sensitivity tests before administration of
antimicrobial drugs.
.
17. 4- Super infection :
Elimination of normal flora by antibiotics will result in Super
infection by drug resistant organisms e.g.
-Staphylococci, leading to staph enterocolitis.
-Clostridium.difficile leading to enterocolitis.
- Candida leading to oral thrush & vulvovaginitis
18. ANTIBIOTIC COMBINATION
Using two or more antibiotics simultaneously, is
indicated in following conditions :-
1- Severely ill patients suspected to have serious
microbial disease e.g. staphylococcal and gram
negative sepsis in immunocompromized patients
, or bacterial meningitis in children.
2- To delay the emergence of drug resistant
mutants e.g. T.B.
3- Mixed infections ; each drug is aimed at an
important pathogen.
19. EFFECT OF COMBINATION
1-Indifference: the combined action is not greater
than that of the more effective one when used
alone
2- Antagonism: the combined action is less than
that of the more effective one when used alone
3-Addition: the combined action is equivalent to the
sum of action of each drug when used alone.
4-Synergism: the combined action is significantly
greater than the sum of both drugs effects
20. CHEMOPROPHYLAXIS
Is the administration of antimicrobials to
Prevent occurrence of infection by
organism e.g.:
1- Use of penicillin or erythromycin before
dental procedures to prevent bacterial
endocarditis in persons with abnormal
heart valves.
2- Use of long-acting penicillin to prevent
recurrent throat infections with
Strept.pyogens & rheumatic heart.
21. 3- Use Riphampicin to the contacts of a case of
epidemic cerebrospinal meningitis.
4-the use of tetracycline to prevent cholera.
5- In surgery: In clean operations(e.g. hernia) there
is no need for chemoprophylaxis but in large
bowel surgery, grossly infected compound bone
fracture and major cardiac surgery, the use of
pre and post- operative antibiotics are
recommended.
22. Host Parasite Relationship
There are three levels of relationships:-
1- Commensalism: The organism (parasitize) or
colonize the host at different sites of the body, where
a balance is achieved between them with only minor
changes of the host. Neither the host nor the parasite
is harmed.
23. 2- Infection: The organism establishes and
colonizes the host ,can elicit an immune response
but very minimal tissue damage and no clinical
signs and symptoms of the disease.
3- Disease: The establishment and colonization of
the organisms into the host, development of an
immune response and marked tissue damage
and/or disturbance of the physiologic functions
of the host enough to elicit the signs and
symptoms of the disease.
24. Factors affecting Host Parasite Relationship :
A- Microbial factors B-Host factors.
A- Microbial factors :
Organism can be classified according to its habitat and its
relationship with the host into:
25. 1- Saprophytic bacteria: are those which live freely in
nature( on decaying organic matter, in soil or in
water).
2- Opportunistic pathogens: bacteria that can not
cause disease under normal conditions but in
immunocompromized or when they are
commensals that find their way to another site
than their normal habitat.
26. 3- Pathogenic bacteria:
bacteria which can cause disease.
Pathogenicity : it’s the capability of the
organism to cause disease (qualitative
description of a of bacterial species
,denoting its ability to produce disease) .
Virulence is a quantitative character which
is the degree of pathogenicity of strain
belonging to a pathogenic species.
27. The Virulence factors of bacteria
1- Adherence factors:
Certain bacteria have specialized structure .e.g.
I-fimbria of Neisseria. gonorrhea & E.coli, allow them adhere to mucus
membrane of urinary tract ,establish themselves & colonize the host
tissue.
II- capsule (e.g., glycocalyx) allows bacteria ( Strept.mutans) to adhere to
the teeth enamel promoting their ability to produce dental caries).
2- Invasive factors:
Organism invasion into the tissues followed by inflammation, then bacteria
can cause the disease. This invasion is helped by:
28. a- Enzymes: Collagenase &hyaluronic acid allow
bacterial infection to spread through
subcutaneous tissues(Strept.pyogenes).
b- capsule (antiphagocytic factor): e.g. capsule of
pneumococci are antiphagocytic.
3- Toxin production:
Toxigenicity: it’s the ability of the organism to
produce toxins and to cause disease.
Can be either exotoxin or endotoxin.
The major difference between the two types of toxin
are outlined in the following table:-
29. Exotoxin
1-Secreted by living
organisms mainly Gram
positive
2- Protein in nature
3- Highly toxigenic
4- Highly antigenic.
5- Can be converted to
toxoid.
6- Every individual exotoxin
has its specific action
7- Unstable to temperature
above 60Ċ
Endotoxin
1-It’s the integral part of the
cell wall of Gram-negative
organism liberated upon
cell disintegration
2- lipo-polysaccharide
3- Low toxigenicity
4- Poorly antigenic.
5- Cannot converted to
toxoid.
6- All endotoxins give fever
& shock.
7- Stable to temperature above
60 Ċ and for several hours.
.
30. Toxoid: Is the treatment of exotoxin in
formalin for one month ,to remove toxicity
and keep antigenicity.
An example of toxigenic bacteria producing
exotoxins is:
Corynebacterium. diphtheria
Clostridium. tetani.
31. B-Host factors:
The most important host factor that determine
the outcome of the host parasite relationship
is the resistance or immunity of the host
whether natural or acquired.
32. Clinical Stages of infectious disease :
1- The incubation period:
it’s the interval between entry of an organism
into a susceptible host and the onset of illness.
33. 2- The phase of illness:
The phase with the characteristic symptoms
and signs following the incubation period.
3- The period of convalescence: Which occur
after the illness subsides.
34. According to duration of illness:
1- Acute illness; rapid onset short duration of
illness.
2- Chronic illness: Develop more slowly
( gradual onset) & long duration.
3- Latent infections: Organism is never completely
eliminated from the body, become reactivated
when the immune response is weakened.
Carrier: individual , harboring infectious agents
for long period of time (months or years)
spreads the pathogen continually even though
they show no signs or symptoms of the disease.
36. Chain of infection
1-Infectous agent ( organism).
2- Reservoir: man, or animal or soil.
3- portal of exit: e.g., : vomiting, diarrhoea,
saliva(Alimentary) & sexual contact
(Genitourinary)and droplets(Respiratory tract).
3-Mode of transmission: e.g., inhalation, ingestion
or direct contact.
1-
37. 4-Portal of Entry into the host respiratory tract,
Gastrointestinal tract , Genitourinary tract, and
skin , organism start to multiply causing disease
.
5-portal of exit: urine, stools , & genital
secretions(discharge), which transmitted to new
host.
- Susceptible host
