Antimicrobial Chemotherapy

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 pathogens 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