Antimicrobial Chemotherapy The Development of Chemotherapy General Characteristics of...
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Antimicrobial Chemotherapy
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
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
The Development of Chemotherapy
Sulfa drugs: 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
The Development of Chemotherapy
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
General Characteristics of Antimicrobial Drugs
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
Dilution Susceptibility Tests Disk Diffission tests Etest Measurement of Drug Concentration in the Blood
Mechanisms of Antibacterial Drug Action
Prescott, table 35.4
Factors Influencing Effectiveness
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
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