1. Chapter 10 Antimicrobial Medications

2. Chemotherapy
Antibiotic
Synthetic drugs
Semi-synthetic drugs

3. In 1910, Paul Ehrlich discovered Salvarsan
Arsenic derivative used to treat syphilis
In 1935, Gerhard Domagk discovered a red dye that inhibited G+ bacteria
Prontosil
In 1936, Ernest Fourneau discovered it was the sulfur portion of the dye that was active
stimulated the development of sulfa drugs

4. In 1928, Alexander Flemming -1st true antibiotic
Penicillium mold secretes compound that inhibits bacterial growth

5. Selman Waksman isolated streptomycin from the soil bacteria Streptomyces
In 1940s, Howard Florey and Ernst Chain performed first clinical trials of penicillin
Developed a method for mass production
Penicillin G

6. More than ½ of antibiotics in use come from bacteria
Primarily species of Streptomyces
Some are isolated from species of Bacillus
Some are isolated from various molds
Penicillium and Cephalosporium
Most antibiotic producers are spore formers

8. Selective Toxicity Magic bullet
causes damage to the microorganism without causing significant harm to the host
Easier with prokaryotic pathogens
Why?

9. Chemotherapeutic index
maximum tolerable dose (per kg body weight) / minimum effective dose (per kg body weight)
Higher the index the safer for host

10. Spectrum of activity
range of different microorganisms against which the drug is effective
Narrow-spectrum
Example – anti-mycobacterials
Broad-spectrum
May disturb normal microbiota
May lead to superinfection

12. Synergism increased effect of two drugs when used together
clavulanic acid and amoxicillin

13. Antagonism
reduction of a drug’s desirable effect when administered with another
penicillin and tetracycline

14. Adverse effects of antimicrobials
Allergic reactions
Toxic effects
Suppression of normal flora

15. Primary Modes of Action

16. Inhibition of Cell Wall Synthesis
Bacterial cell walls are composed of the polysaccharide peptidoglycan
Some antibiotics prevent the synthesis of intact peptidoglycan
Human cells are unaffected

17. Disruption of Cell Membrane
changes permeability of the plasma membrane
Results in the loss of important metabolites
May target specific membrane components
Ex. particular sterols in fungi cell membranes

18. Inhibition of Protein Synthesis
Common feature of all cells
May target the ribosomes
Change ribosome shape
Block binding sites for tRNA/rRNA
Inhibit peptide bond formation
Prevent shift of reading frame
Use is limited

19. Inhibition of Nucleic Acid Synthesis
Interfere with DNA or RNA synthesis
May act as nucleoside/nucleotide analogs
Some have an extremely limited usefulness
Others are widely used because they are more selectively toxic
May act only on bacterial or viral enzymes

21. Metabolic Antagonists
Inhibition of the synthesis of essential metabolites
enzymatic activity of microbes can be inhibited by a substance that closely resembles the normal substrate for the enzyme
Competitive inhibition

23. Inhibition of Host Recognition or Attachment
Depends on chemical reaction between pathogen and host
Pathogen proteins and specific host receptors
Modification of either attachment or receptor proteins can inhibit attachment and entry

24. Mechanisms for Administration of Drugs
Topical
Orally
Intramuscularly (IM)
Intravenously (IV)

25. Tests to Guide Chemotherapy
Disk-diffusion method (Kirby-Bauer test)
Minimum Inhibitory Concentration tests (MIC)
E-test
Minimum Bactericidal Concentration tests (MBC)

26. Kirby-Bauer Test

27. MIC Test

28. E Test

29. MBC Test