1. 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

2. 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

3. 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

4. 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

5. 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

6. Detemining the level of Antimicrobial Activity • Dilution Susceptibility Tests • Disk Diffission tests • Etest • Measurement of Drug Concentration in the Blood

7. Mechanisms of Antibacterial Drug Action • Prescott, table 35.4

8. 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

9. 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