Transcript Antimicrobial Chemotherapy

Antimicrobial Chemotherapy
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The Development of Chemotherapy
General Characteristics of Antimicrobial Drugs
Determining the Level of Antimicrobial Activity
Mechanisms of Antibacterial Drugs
Factors Influencing Effectiveness
Drug Resistance
The Development of Chemotherapy
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Early 20th century
1904: Ehrlich found that the dye trypan red was
effective against Trypanosoma (sleeping sickness)
 Arspheniamine (Salvarsan) against syphilis
 Quinine against malaria
 Various dyes (including gentian violet); disinfectants;
heavy metals were tried as antimicrobial
chemotherapeutic agents
 Antisera were also used; for example, anti-sterptococcal
antisera used against scarlet fever
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The Development of Chemotherapy
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Sulfa drugs:
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1927: Domagk discovered that the dye Prontosil Red
was effective against staphlococcal and streptococcal
infections; later in 1935 it was found that Protonsil red
was converted to sulfonamide in the body
Penicillin
Produced by Penicillium notatum
 Discovered in 1928 by Fleming
 Method of mass production developed in late 1930s early 1940s by Chain and Florey
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The Development of Chemotherapy
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Streptomycin
Produced by Streptomyces griseus
 Discovered in 1944 by Waksman after screening 10,000
soil isolates
 Following its discovery was the discovery of other
antibiotics produced by soil microbes, including
chloramphenicol, neomycin, terramycin, and tetracyclin
by the early 1950s
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General Characteristics of
Antimicrobial Drugs
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Selective toxicity
Therapeutic dose
Toxic Dose
Therapeutic Index
Side Effects
Narrow-Spectrum
Broad Spectrum
Cidal vs Static
Minimal Inhibitory Concentration
Minimal Lethal Concentration
Detemining the level of
Antimicrobial Activity
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Dilution Susceptibility Tests
Disk Diffission tests
Etest
Measurement of Drug Concentration in the Blood
Mechanisms of Antibacterial
Drug Action
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Prescott, table 35.4
Factors Influencing Effectiveness
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Ability of the drug to reach the site of infection
Route of administration
Rate at which the drug is eliminated from the body
Susceptibility of the pathegen to the drug
Level of the drug must exceed the pathogen’s MIC
value at the site of infection
Drug Resistance
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Mechanisms of Drug resistance
Origin of Drug Resistance in a microbial
population
Drug resistance genes on chromosomes and
plasmids
Transmission of resistance genes between bacteria