1 ANTIMICROBIAL THERAPY CHAPTER 13

2 Chemotherapeutic Agents Antibiotics: bacteriocidal vs bacteriostatic Synthetic Drugs vs natural product

3 History Ancient remedies Ehrlich Domagk Fleming

4 Properties of Antimicrobial Agents Selective Toxicity Spectrum of Activity –Narrow –Broad

5 Spectrum of Activity

6 Drug Mechanisms of Action Inhibition of Cell Wall Synthesis Disruption of Cell Membrane Function

7 Drug Mechanisms of Action Inhibition of Protein Synthesis Inhibition of Nucleic Acid Synthesis Antimetabolites

8 Summary of Targets

9 Side Effects Toxicity Allergy Disruption of Microflora

10 Classes of antibiotics Aminoglycosides Tetracyclines Sulfonamides Quinolones Polypeptides B-lactams Macrolides Glycopeptides Cephalosporins

11 aminoglycosides kanamycin, neomycin, amikacin Binds 30 S ribosome

12 tetracyclines Tetracycline, Doxycycline Binds 30 S ribosome

13 sulfanamides Sulfacetamide Trimethoprim Sulfamethizole Folate synthesis inhibition. They are competitive inhibitors of the enzyme

14 B-lactams Amoxicillin Carbenicillin Penicillin Ampicillin disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

15 quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme

16 polypeptides bacitracin Polymyxin B Inhibits isoprenyl pyrophosphate Interacts with the bacterial cytoplasmic membrane, changing its permeability.

17 macrolides Azithromycin Clarithromycin Spectinomycin Erythromycin Binds to 50s ribosome

18 Glycopeptides Vancomycin- last resort drug inhibiting peptidoglycan synthesis

19 cephalosporins Cefaclor Cefalexin Ceftobiprole Cefotaxime Same mode of action as other beta- lactam antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

20 Resistance to Drugs Chromosomal - Klebsiella B lactamases Plasmid borne - ribosomal protein mutations

21 Mechanisms of Drug Resistance Mutations in Target molecules Alterations in membrane permeability Enzyme development

22 Fig Phosphorylation Adenylation Streptomycin Chloramphenicol  -Lactamase Penicillin Acetylation

23 Table 27-7

24 Mechanisms of Drug Resistance Enzyme Activity Changes Alterations in Anabolic Pathways

25 Generations of Drugs First/Second/Third Line Drugs Cross Resistance

26

27 Limiting Drug Resistance Effective Drug Concentrations Simultaneous Drug Administration Synergism - clavulanic acid Antagonism - Restricting Drug Prescriptions

28 Determining Microbial Sensitivities Disk Diffusion Method Dilution Method Serum Killing Power Automated Methods

29 Ideal Antimicrobial Attributes Solubility Selective toxicity Stable toxicity level Allergenicity Tissue stability Resistance Acquisition Shelf Life Cost

30 Antibacterials — Cell Wall Target Penicillins

31 Antibacterials — Cell Wall Target Cephalosporins Carbapenems

32 Antibacterials — Cell Membrane Target Polymyxins

33 Antibacterials — Protein Synthesis Inhibition Aminoglycosides Tetracyclines Chloramphenicol Macrolides Insert Fig

34 Antibacterials — Nucleic Acid Synthesis Inhibition Rifampin Quinolones

35 Antibacterials — Antimetabolites Sulfonamides Isoniazid Ethambutol Nitrofurans

36 Antifungals Imidazoles Polyenes Griseofulvin

37 Antifungals Flucytosine Tolnaftate Terbinafine

38 Antivirals Nucleotide analogs

39 Antivirals Amantidine/Rimantidine Interferons/Immunoenhancers

40 Antiprotozoan Drugs Quinine/derivatives Metronidazole Pyrimethamine Suramin

41 Antihelminthic Drugs Niclosamide Mebendazole Ivermectin

42 Special Drug Resistance Problems