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