1. Chapter 15: Antimicrobial Drugs ChemotherapyThe use of drugs to treat a disease Antimicrobial drugsInterfere with the growth of microbes within a host Antibiotic Inhibits “bacterial” growth; usually produced by bacteria or fungi Selective toxicityKills harmful microbes without damaging the host

2. Broad-spectrum antibiotic Superinfection Bactericidal antibiotic Bacteriostatic antibiotic

3. 1928 – Fleming discovered penicillin; produced by Penicillium (a fungus). 1940 – First clinical trials of penicillin. Figure 20.1 The First Antibiotic

4. Table 20.2

5. Antimicrobials and Modes of Action Prevents cell wall synthesis Prevents protein synthesis Plasma membrane attack Prevents nucleic acid synthesis Disrupts biochemical pathways

6. Penicillin Natural penicillins Narrow spectrum Use for Staphylococci, Streptococci, Spirochetes Vulnerable to penicillinases (beta lactamases) Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

7. Figure 20.8 Some bacteria can disrupt the functioning of penicillin

8. Penicillins Figure 20.6

9. Semisynthetic penicillins Penicillinase-resistant penicillins First was methicillin Extended-spectrum penicillins Effective against many Gram negatives Some effective against Pseudomonas aeruginosa Penicillins +  -lactamase inhibitors

10. Cephalosporins: more effective against gram- negatives than natural penicillins Figure 20.9 Vancomycin: Used against antibiotic resistant S. aureus (i.e. MRSA) VRE have emerged

11. Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16a

12. Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16b, c

13. Protease inhibitors Entry and Uncoating inhibitors Viral release inhibitors i.e. Tamiflu Interferons, prevent spread of viruses to new cells Common treatment for Hepatitis C infection Antiviral Drugs

14. Kirby-Bauer (Disk-Diffusion) Test Antibiotic soaked disks are placed on cultured plate Zone of inhibition is measured and compared to table with known results

15. E test Antibiotic gradient strip is placed on cultured plate Minimal inhibitory concentration (MIC) is determined

16. E Test Figure 20.18

17. Broth Dilution Test Can distinguish between MIC and MBC (minimal bactericidal concentration)

18. Mechanisms of antibiotic resistance Alteration of drug's target site Rapid ejection of the drug Enzymatic destruction of drug Prevention of penetration of drug Antibiotic Resistance

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antibiotic Resistance A variety of mutations can lead to antibiotic resistance. Resistance genes are often on plasmids or transposons that can be transferred between bacteria.

20. Misuse of antibiotics selects for resistant mutants. Misuse includes: Using outdated, weakened antibiotics Using antibiotics for the common cold and other inappropriate conditions Use of antibiotics in animal feed Failure to complete the prescribed regimen Using someone else's leftover prescription Antibiotic Resistance

21. Synergism: occurs when the effect of two drugs together is greater than the effect of either alone. Antagonism: occurs when the effect of two drugs together is less than the effect of either alone. Effects of Drug Combinations

22. Effects of Combinations of Drugs Figure 20.22