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Antibiotics

• Definition: • narrow-spectrum
antimicrobial drugs – attack only a
substances formed few different
by microorganisms pathogens
that kill (e.g.
bactericidal effect) or • broad-spectrum
inhibit (e.g. drugs – attack many
bacteriostatic effect) different pathogens
other
microorganisms.
• cidal agent - kills
microbes

• static agent - inhibits


growth of microbes

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The golden age of microbiology (1857-1914)
Treatment of human infections with antibiotics was a medical revolution.

Koch’s postulates
- The microorganism must be
present in every case of the
disease but absent from
healthy individuals.
- The suspected
microorganism must be
isolated and grown in a pure
culture.
- The same disease must
result when the isolated
microorganism is inoculated
into a healthy host.
- The same microorganism
must be isolated again from
the diseased host.

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• selective toxicity
– ability of drug to kill or inhibit pathogen while
damaging host as little as possible
• therapeutic dose
– drug level required for clinical treatment
• toxic dose
– drug level at which drug becomes too toxic for
patient (i.e., produces side effects)
• therapeutic index
– ratio of toxic dose to therapeutic dose

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Penicillin accidentally discovered
by Alexander Fleming (1928)

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Micelle-forming bacteria

The genus Streptomyces includes about 500 species.


Constitutes 1-20% of the cultivable earth flora.
Forms geosmin, or earth smell, and a large number of antibiotics.

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Antibiotics can be divided into four groups
based on their biochemical mechanisms:
1. those that inhibit the synthesis of cell walls
(peptidoglycan)
2. those that inhibit protein synthesis (the
ribosome)
3. those that inhibit nucleotide synthesis
(nucleotides, DNA, RNA)
4. those that affect the plasma membrane.

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Sensitivity tests
• The sensitivity of
microorganisms to
antibiotics can be
investigated with the MIC
(minimum inhibitory
concentration) and the MLC
(minimum lethal
concentration) tests.

• effectiveness expressed in
two ways
– minimal inhibitory Disk Diffusion Tests
concentration (MIC)
• lowest concentration disks impregnated with
of drug that inhibits specific drugs are
growth of pathogen
– minimal lethal
placed on agar plates
concentration (MLC) inoculated with test
• lowest concentration microbe
of drug that kills
pathogen

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Dilution Susceptibility Tests

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Resistance to antibiotics is divided into
natural resistance and acquired resistance
• an increasing problem
• once resistance originates in a population it can be
transmitted to other bacteria
• resistance mutants arise spontaneously and are then
selected
• Resistance to antibiotics can be acquired by
mutation or recombination (e.g. plasmids).

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Mechanisms of Drug Resistance
• detoxification of the antibiotic (modification or
inactivation of the active substance)
• changes in the target structure
• alternative target structure (enzymes)
• increased amount of enzyme or substrate
• alternative synthesis route
• changes in the permeability

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Transmission of Drug Resistance

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Preventing emergence of drug
resistance
• reduced use of
antibiotics
• sensitivity tests
• other kinds of
treatment
• give drug in high
concentrations
• give two or more
drugs at same time
• continued
development of new
drugs
– etc

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