1. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PowerPoint ® Lecture Slide Presentation prepared by Christine L. Case Microbiology B.E Pruitt & Jane J. Stein AN INTRODUCTION EIGHTH EDITION TORTORA FUNKE CASE Chapter 20, part A

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antimicrobial Drugs ChemotherapyThe use of drugs to treat a disease Antimicrobial drugsInterfere with the growth of microbes within a host AntibioticSubstance produced by a microbe that, in small amounts, inhibits another microbe Selective toxicityA drug that kills harmful microbes without damaging the host

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Ehrlish the magic bullet 1928 – Fleming discovered penicillin, produced by Penicillium. 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1

4. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Table 20.1

5. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Spectrum of antibiotics Narrow spectrum Broad spectrum

6. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Table 20.2

7. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Broad-spectrum Superinfection Bactericidal Bacteriostatic

8. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Figure 20.2

9. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Figure 20.4

10. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillin Natural penicillins Penicillin G excreted 3-6 hours Procine Penicillin stable 24 hours Benzathine Penicillin 4 month Penicillin V stable in stomach Semisynthetic penicillins Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

11. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillins Figure 20.6

12. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillin Penicilinase-resistant penicillins Methicillin Oxacillin Extended-spectrum penicillins aminopenicillin like Carbenicillin Uridopenicillin like azocillin Penicillins +  -lactamase inhibitors amoxicillin and calvulanic acid (Augmentin) Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

13. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.8 B lactam ring+thiazolidine ring

14. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Carbapenems broadest antibacterial spectrum compared to other beta-lactam classes such as penicillins. Meropenem Monobactam Aztreonam Synthetic antibiotics

15. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cephalosporins 2 nd, 3 rd, and 4 th generations more effective against gram-negatives Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.9 dihydrothiazine ring thiazolidine ring

16. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cephazolin, cephalothinFirst generation Cefaclore, cefuroximeSecond generation Ceftriaxone, Ceftaxime, CeftazidiumThird generation CefepimeFourth generation

17. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polypeptide antibiotics Bacitracin Topical application Against gram-positives Vancomycin Glycopeptide Important "last line" against antibiotic resistant S. aureus Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

18. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antimycobacterium antibiotics Isoniazid (INH) Inhibits mycolic acid synthesis Ethambutol Inhibits incorporation of mycolic acid Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Tetracyclines Broad spectrum bacteristatic, Interferes with tRNA attachment Tetracycline, deoxycycline, minocycline Act against intracellular bacteria as Rickettsia, Chlamydia. Not used with children, pregnant women. Antibacterial Antibiotics Inhibitors of Protein Synthesis

20. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Aminoglycosides Streptomycin, neomycin, gentamycin Broad spectrum Changes shape of 30S sbuunit Gentamicin, Amikacin, Streptomycin most common. Effect on kidney and auditory nerve.

21. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Chloramphenicol Broad spectrum, bacteriostatic Binds 50S subunit, inhibits peptide bond formation Macrolides Gram-positives Binds 50S, prevents translocation Erythromycin Gram-positives Binds 50S, prevents translocation, bacteriostatic Antibacterial Antibiotics Inhibitors of Protein Synthesis

22. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polymyxin B Peptide derivatives One end of molecule water soluble and the other end is hydrophobic. Topical Bactericidal Gram negative Antibacterial Antibiotics Injury to the Plasma Membrane

23. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polyens amphotericin B and Nystatin The most important. Act against fungi by binding to ergosterol.

24. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Rifamycin Inhibits RNA synthesis inhibits DNA-dependent RNA polymerase Anti tuberculosis Narrow spectrum Gram positive. Quinolones and fluoroquinolones Nalidixic acid, gram negative, UTI Ciprofloxacin, Broad spectrum, bactericidal Inhibits DNA gyrase Urinary tract infections Not used with children or pregnant Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis

25. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Sulfonamides (Sulfa drugs) Inhibit folic acid synthesis Broad spectrum Antibacterial Antibiotics Competitive Inhibitors Figure 5.7

26. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20.13

27. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Disk-Diffusion Test Figure 20.17

28. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings E Test Figure 20.18

29. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MIC Minimal inhibitory concentration MBC Minimal bactericidal concentration

30. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Broth Dilution Test Figure 20.19

31. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings A variety of mutations can lead to antibiotic resistance. Mechanisms of antibiotic resistance 1. Enzymatic destruction of drug 2. Prevention of penetration of drug 3. Alteration of drug's target site 4. Rapid ejection of the drug Resistance genes are often on plasmids or transposons that can be transferred between bacteria. Antibiotic Resistance

32. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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. Autonomous or indifferent. WHY!!!!!!!!!!!!!!! Effects of Combinations of Drugs

33. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Who to choose antibiotics Figure 20.22

34. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antimicrobial peptides Broad spectrum antibiotics from plants and animals Disrupts permeability of microbial membrane. Squalamine (sharks) Protegrin (pigs) Magainin (frogs) Antisense agents Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription The Future of Chemotherapeutic Agents

35. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings