Chapter 10 Antimicrobial Medications

1. Chapter 10Antimicrobial 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