ANTIBIOTICS

1. ANTIBIOTICS From the Greek: anti - against bios - life

2. Chemotherapy • Paul Ehrlich • Use of chemical agent to kill bacteria and not harm the host • Search for the “Magic bullet” • Developed an arsenic compound that killed the bacteria that causes syphilis • Compound was called salvarsan but was quite toxic to the host

3. Antibiotics • Natural compounds produced by microorganisms that inhibit the growth of other microbes • Majority of antibiotics come from Streptomyces bacteria and molds • Over 100 different antibiotics • Antibiotics generally have two names • Brand name created by the drug company • Generic name based on the chemical structure or class of antibiotics

4. Famous penicillin picture

5. Alexander Fleming • Discovered penicillin by accident in 1928 • A mold contaminating a plate of Staphylococcus aureus showed anti-bacterial properties • The mold was identified as a member of genus Penicillum, hence the name for the naturally produced antibiotic • Fleming won the Nobel prize in 1945 for this discovery, shared with Howard Florey and Ernst Chain

6. Wonder drug Killed bacteria with few side effects on the patient SELECTIVE TOXICITY Penicillin was NOT the first anti-bacterial compound Penicillin was the FIRST natural compound that kills bacteria Antibiotic Not made in the lab Penicillin

7. Broad spectrum antibiotics Effect both G+ and G- bacteria Tetracycline Narrow spectrum antibiotics Effects fewer types of pathogens More selective? Penicillin – best against G+ bacteria Spectrum of Activity

8. How do antibiotics work?

9. Cell Wall Synthesis • Penicillin • Prevents synthesis of the peptidoglycan components of the cell wall • Targets actively growing cells • Very little toxicity to human cells

10. Inhibition of protein synthesis • Broad spectrum of activity – all bacteria have to make proteins • Difference in ribosome size in bacteria accounts for selective toxicity • Chloramphenicol, erythromycin (G+), streptomycin, tetracyclines

11. Injury to plasma membrane • Changes to permeability of membrane causes loss of metabolites • Polymyxin B

12. Inhibition of nucleic acid synthesis • Inhibition if either DNA replication or mRNA synthesis • Toxicity problems • Rifampin – mRNA blocker • Nofloxacin and ciprofloxacin – DNA synthesis blockers

13. Inhibition of synthesis of essential metabolites • Block enzyme activity • Competitive inhibition of enzyme activity • PABA (para-aminobenzoic acid) competition • Sulfonamides

14. Sulfonamide P-aminobenzoic acid Metabolite Inhibition

15. Commonly used antibiotic types • Penicillins • Cephalosporins • Animoglycosides • Macolides • Sulfonamides • Fluoroquinolones • Tetracyclines • Polypeptides

16. Penicillin • Destroys the cell wall of bacteria • Best against G+ bacteria during active growth • Examples: • Penicillin G • Penicillin V • Ampicillin • Amoxicillin

17. Cephalosprorins • Similar to penicillin - interferes with cell wall formation • Used when patient is allergic to penicillin • Examples • Cefadroxil • Cephapirin • Cephalexin • Cephalothin

18. Aminoglycosides • Inhibition of protein synthesis in bacteria • Some toxic reactions possible in kidney and liver • Examples • Gentamicin • Streptomycin • Neomycin

19. Macrolides • Interfere with bacterial protein synthesis • Commonly given to patients that are sensitive to penicillin • Gastrointestinal discomfort is a common side effect • Examples • Azithromycin • Erthromycin

20. Sulfonamides • Very early antimicrobial substance • Commonly called sulfa drugs • Developed in the 1930’s in Germany • Mode of action is enzyme inhibition • Allergy to sulfa is common

21. Fluoroquinolones • Large class of semi-synthetic broad spectrum antibiotics • Inhibition of bacterial DNA replication • Few side effects, well tolerated • Examples • Ciprofloxacin • Norfloxacin

22. Tetracycline Antibiotics • Members of this group of antibiotics are produced by Streptomyces group of bacteria • Inhibition of protein synthesis • Used commonly to treat acne • Examples • Tetracycline • Deoxycycline

23. Penicillin

24. Penicillinase

25. Cephalosporin Produced from a fungus Similar in action to penicillin More active against G- bacteria More resistant to penicillinase Penicillin Produced from fungus Inhibits cell wall synthesis Effective against mostly G+ bacteria Penicillinase sensitivity Cephalosporin and Penicillin

26. Cephalosporin and Penicillin

27. Adverse reactions • Toxicity • Allergy • Disruption of natural flora • Yeast infections

28. Antibiotic Resistance(A BIG problem) • Resistance is acquired by mutation • R (resistance) plasmids acquired by bacterial conjugation • How to limit resistance • Take all your pills, don’t stop when you feel better • Use antibiotics only when necessary • NEVER take antibiotics for viral infection alone

29. Nosocomial Infections • Infections acquired while in a health care facilities • CDC estimates 2 million people per year get these infections • 90,000 deaths per year

30. Nosocomial Infections

31. Antiviral Drugs • Limited in number • Targets for these drugs are viral reproduction • Nucleotide analogs are the most commonly used agents – disrupt viral nucleic acid replication • Acyclovir

32. Nucleotide analog

33. Sensitivity Testing