Antibiotics and Chemotherapeutic Agents

1. Antibiotics and Chemotherapeutic Agents

2. Chemotherapeutic agents and antibiotics can differ Chemotherapeutic agent - synthetic agents made in the laboratory Antibiotic – compounds made by living organisms

3. Criteria of a good chemotherapeutic agent Selective Toxicity Penetration of both tissues and cells Does Not interfere with host’s natural defenses

4. Sulfanilamide and other sulfonamides interfere with metabolic reactions Competitive inhibition Sulfamethoxazole Sulfisoxazole acetyl

6. Other chemotherapeutic agents Isoniazid - antituberculosis drug Nalidixic acid - blocks DNA sysnthesis in gram – bacteria Nalidixic acid derivatives-fluoroquinolones Cipro Treat gram – infections in both urinary and intestinal tracts Quinine, chloroquine, and primaquine

7. Criteria of a good Antibiotic Destroys a broad spectrum of microorganisms Prevents the development of resistant strains Produces no undesirable side effects Does not interfere with normal flora

8. Sources of antibiotics Bacillus Penicillium Cephalosporium Streptomyces

10. The discovery of antibiotics began with Fleming Penicillin - 1928 Fleming noted that penicillin inhibited gram+ bacteria Florey and Chain - 1940 isolated the actual penicillin molecule.

11. Penicillin inhibits bacterial cell wall synthesis Beta-lactam nucleus Spectrum of activity Development of resistant strains Mode of action

12. A large group of semisynthetic penicillins has been developed Ampicillin Amoxicillin Carbenicillin Methicillin

13. Cephalosporins also inhibit cell wall synthesis Resemblance to penicillins Generations of cephalosoporins Application Penicillin resistance Mode of action – Cell Wall inhibition

15. Aminoglycosides inhibit protein synthesis Chemical structure – amino acids bonded to glycosides (carbohydrate molecules) Mode of action – ribosomal attachment Examples of Aminoglycosides Streptomycin Gentamicin Kanamycin

16. Antibiotic Action on Protein synthesis

17. Chloramphenicol alsoinhibits translation Discovery – 1947 beginning of Broad Sectrum Spectrum of activity Mode of action – Binds to 50S unit of Ribosome Aplastic anemia

18. Antibiotic Action on Protein synthesis

19. Tetracyclines are another group of drugs that affect protein synthesis Origin – 1947 chlortetracycline Spectrum of activity - broad Mode of action – interferes with tRNA to mRNA binding

20. Antibiotic Action on Protein synthesis

21. Other antibiotics have a variety of effects Erythromycin Vancomycin Rifampin Bacitracin Polymyxin B

22. Antibiotic Action on Protein synthesis

24. Antifungal antibiotics can produce toxic side effects Nystatin – Candida albicans infections Amphotericin B – systemic fungal infections (degrades cell membrane)

25. Antiviral agents inhibit theviral replication cycle Modes of action Amantadine and zanamivir Acyclovir and ganciclovir AZT and ribavirin Nevirapine and delavirdine Saquinavir and ritonavir Interferons

26. There are four mechanisms of antibiotic resistance Mechanisms Altered metabolic pathway Antibiotic inactivation Reduced permeability/active export Faulty transport system Efflux system Target modification Altered binding proteins Altered ribosomal target Altered enzyme Hyper-production of target

28. Antibiotics have been misused and abused Evolving resistance in bacteria Antibiotic misuse and abuse Society Hospitals Livestock feeds

29. Transmission of resistance Conjugation Transformation Transduction

30. Minimization of resistance Avoid using antibiotics when not needed Don’t use generalized infection antibiotics for topical applications Use high enough dose Don’t mix antibiotics When resistance is evident switch antibiotics

31. There are several antibiotic susceptibility assays Tube dilution method Agar disk diffusion method

32. Kirby Bauer

33. Tube Dilution