1. Antibiotics

2. Definition any of a variety of substances, usually obtained from microorganisms, that inhibit the growth of or destroy certain other microorganisms.

3. History Pasteur observed that other bacteria had antagonistic effects on the bacteria responsible for anthrax German chemist Paul Ehrlich developed the idea of selective toxicity: that certain chemicals that would be toxic to some organisms

4. History cont’d In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture.

5. History 1939, microbiologist René Dubos – found that Bacillus brevis from soil inhibited pneumococcus growth – with tyrothricin (but toxic to human cells) Penicillin was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin and a number of other antibiotics from Streptomyces griseus.Penicillinstreptomycin

6. History Penicillin was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin and a number of other antibiotics from Streptomyces griseus.Penicillin streptomycin

7. Antibiotics today The antibiotics we take today are still produced by bacteria in large fermentation tanks…. Some are synthetic….but much more expensive

8. Classification Antibiotics can be classified in several ways, for example: 1.Spectrum 2.Modes of action 3.Chemical structure -

9. Spectrum Broad They target a range of bacteria (gram +ve and –ve) Uses: -If pathogen is not identified -For superinfections Examples: Amoxicillin, tetracycline, streptomycin -

10. Antibiotic spectrum Narrow - Target only a group of bacteria usually once the pathogen is identified - Good for preventing antibiotic resistance Eg. vancomycin

11. Classification Modes of action Some antibiotics attack the cell wall; some disrupt the cell membrane; and others inhibit the synthesis of nucleic acids and proteins.

12. Penicillin All penicillin like antibiotics inhibit synthesis of peptidoglycan, an essential part of the cell wall. They do not interfere with the synthesis of other intracellular components. The continuing buildup of materials inside the cell exerts ever greater pressure on the membrane, which is no longer properly supported by peptidoglycan. The membrane gives way, the cell contents leak out, and the bacterium dies. These antibiotics do not affect human cells because human cells do not have cell walls.

13. Mechanisms of Action Many antibiotics operate by inhibiting the synthesis of various intracellular bacterial molecules, including DNA, RNA, ribosomes, and proteins. The synthetic sulfonamides are among the antibiotics that indirectly interfere with nucleic acid synthesis. Some antibacterials affect the assembly of messenger RNA, thus causing its genetic message to be garbled. When these faulty messages are translated, the protein products are nonfunctional.

14. Classification by chemical structure Beta-Lactams –Penicillins –Cephalosporins Macrolides Fluoroquinolones Tetracyclines Aminoglycosides

15. Administration and Side Effects Administration Injected, given orally or topically-applied Side effects -Allergies -Skin rashes -Fever, nausea, diarrhea -Changes in intestinal bacteria

16. Production of Antibiotics mass production during World WarII with streptomycin and penicillin now antibiotics are produced by fermentations with high-yielding microorganisms producing high yields are grown under optimum conditions

17. Production of Antibiotics Some new antibiotics are laboratory synthesized, while many antibiotics are produced by chemically modifying natural substances some semi-synthetic penicillins are effective against bacteria resistant to the parent substance. E.g. amoxycillin

18. Antimicrobial Resistance Relative or complete lack of effect of antimicrobial against a previously susceptible microbe

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

20. Antibiotic Selection for Resistant Bacteria

21. What Factors Promote Antimicrobial Resistance? Exposure to sub-optimal levels of antimicrobial Exposure to microbes carrying resistance genes

22. Inappropriate Antimicrobial Use Prescription not taken correctly Antibiotics for viral infections Antibiotics sold without medical supervision Spread of resistant microbes in hospitals due to lack of hygiene

23. Inappropriate Antimicrobial Use Lack of quality control in manufacture or outdated antimicrobial Inadequate surveillance or defective susceptibility assays Poverty or war Use of antibiotics in foods

24. Antibiotics in Foods Antibiotics are used in animal feeds and sprayed on plants to prevent infection and promote growth Multi drug-resistant Salmonella typhi has been found in people who ate beef fed antibiotics

25. Consequences of Antimicrobial Resistance Infections resistant to available antibiotics Increased cost of treatment

27. Multi-Drug Resistant TB

28. MRSA “mer-sah” Methicillin-Resistant Staphylococcus aureus Most frequent nosocomial (hospital-acquired) pathogen Usually resistant to several other antibiotics

29. Vancomycin Resistant Enterococci

30. Vancomycin Use USA

31. Proposals to Combat Antimicrobial Resistance Speed development of new antibiotics Track resistance data nationwide Restrict antimicrobial use Direct observed dosing (TB)

32. Proposals to Combat Antimicrobial Resistance Use more narrow spectrum antibiotics Use antimicrobial cocktails