Chemotherapy
CHEMOTHERAPY
Antibiotics are substances
produced by microorganism,
which suppress the growth of or
kill other microorganisms at
very low concentrations.
Classification of Antibiotics
Chemical Structure
Spectrum of Activity
Mechanism of Action
Classification of Antibiotics
bacteriostatic, i.e. those that act primarily by
arresting bacterial multiplication, such as
sulphonamides, tetracyclines &
chloramphenicol
bactericidal, i.e. those which act primarily by
killing bacteria, such as penicillins,
cephalosporins, aminoglycosides, isoniazid
and rifampicin.
Drug Resistance
Natural resistance
Acquired resistance
Mutation
Gene transfer
Natural resistance
Microbes always been resistant to certain
antimicrobial agents (AMA)
Lack metabolic process/target site
Eg: M.tuberculosis is insensitive to
tetracyclines
Acquired resistance
Development of resistance by an
organism (which is sensitive before) due
to use of an AMA over a period of time
Happen with any microbe & major
clinical problem
Eg: Gonococci to sulfonamides
Mutation
Stable & heritable change that occurs
spontaneously
Not induced by AMA
Mutation & resistance may be single/multi step
Gene Transfer
Conjugation
Transduction
Transformation
Chromosomal vs. R Plasmid Encoded
Impermeability
Inactivation
Efflux
R plasmid
R plasmid
B
A
By-pass
Chromosomal mutation
Altered
target
Combination of AMA
To achieve synergism
To reduce severity / incidence of
adverse effects
To prevent emergence of resistance
To broaden spectrum of antimicrobial
action
Disadvantages of Antimicrobial
Combination
↑incidence & variety of adverse effects
Toxicity of one agent can may be enhanced by another
Increase chances of superinfection
↑ cost of therapy
Sulfamethoxazole + Trimethoprim
Rifampicin + Isoniazid
Cephalosporine + Ciprofloxacin
Superinfection
Appearance new infection due to alteration of
normal microbial flora of the body
More complete suppression of body flora
greater chances of superinfection
Commonly associated with the use of broad/
extended spectrum antibiotics
Eg: tetracyclines, chloramphenicol, ampicillin,
newer cephalosporins
Conditions predisposing to
superinfections
Corticosteroid therapy
Leukaemias & other malignancies
Acquired Immuno Deficiency Syndrome
(AIDS)
Agranulocytosis
Diabetes
Failure of antimicrobial therapy
Improper selection of drug, dose, route /
duration of treatment
Treatment begun too late
Failure to take necessary adjuvant measures
Poor host defence ( Leukaemias, neutropenia)
Infecting organism present behind barriers