Anti-bacteria Medicine

1. Anti-bacteria Medicine

2. Anti-bacteria medicine • Antibiotics: The substance derived from fungi and bacteria which can selectively kill or inhibit bacteria growth • Anti-bacteria medicine: Chemically synthesized medicine which can selectively kill or inhibit bacteria growth

4. Antibacteria medicine • Sulfonamide • Quilonones • others

6. Antibiotics and drugs targeting nucleic acid biosynthesis and functions

7. Antibiotics and drugs targeting nucleic acid biosynthesis and functions 1. Sulphonamides & Trimethoprim (TMP) PABA false structure Inhibition of Dihydrofolate reductase Dihydrofolate  tetrahydrofolate

9. Antibiotics and drugs targeting nucleic acid biosynthesis and functions 2. Quinolones Bacterial topoisomerase II- Gyrase • Nalidixic acid • Ofloxacin • Ciprofloxacin

11. Antibiotics and drugs targeting nucleic acid biosynthesis and functions 3. Rifampicin (from rifamycin)  subunit of DNA-primed RNA polymease

12. Antibiotics and drugs targeting nucleic acid biosynthesis and functions ! Rifampicin must be given by a “cocktail” of drugs.

17. Problem of antibiotics which inhibit protein synthesis

19. Antibiotics: From isolation of strain to clinical application • Selection of a potential product 1、efficacy 2、metabolic characterization 3、toxicity and adverse effect 4、Potentiality of industrial production

20. Antibiotics: from strain isolation to clinical application • Semi-synthesis: the most popular approach of production • Marketing potentiality • Life-span of marketing and its impact

22. Patients withpneumonia and bacteria in blood Penicillin % överlevare Penicillin increased the chance of survival from 10% to 90% Obehandlade Dagar

23. “It is not difficult to make microbes resistant to penicillin… “ “The time may come when penicillin can be bought by anyone in the shops“ Alexander Fleming's Nobel Lecture, 1945

25. The Global Challenge Antibioticshavesaved millions of lives Antibiotics are rapidlylosingtheireffect

26. What is Antibiotic Resistance?

27. Bacterial Resistance to Antibiotics  Enzymes secreted (exo-enzyme)  Enzymes not secreted (endo-enzymes)  Deletion of target molecules  Change in cell permeability  Change in target molecule affinity  Speed-up of synthesis and metabolism  Others

28. Mechanism of resistance • Selection pressure ( not only in health institutions) • Genetic recombination ( especially conjugation mediated by plasmid)

29. Improper prescription of antibiotics • Antibiotic prescription for non-bacterial infection • Prophylaxis application of antibiotics • Local application of antibiotics • Over use of wide-spectrum antibiotics • Long-term use of antibiotics • Antibiotic abuse in agriculture production

30. Modern Medicine Is Not Possible Without Effective Antibiotics Hip replacement Organ transplants Cancer chemotherapy Care of preterm babies

31. The survival of the fittest

33. Horisontal spread of resistance genes Spread of resistance between species

34. Barrier to the development of new antibiotics • Short marketing life of the product because of resistance • Difficult R&D 1、qualified strain 2、resources to support R&D 3、long term research and translation • Adverse reactions • Expense for health care

35. The outcome of resistance development (From the view point of bacteria cells)  Uneconomic state of cell metabolism  Slow-down of proliferation  deletion of some pathogenic abilities  Avoiding harms from drugs

37. Antibiotic sensitivity test MIC & MBC  Broth dilution  Agar dilution  Disk diffusion  Standard requirements

39. Antibiotic sensitivity test Standard requirements: a.Depth: 4mm b.  Inoculates: 105 cell/ml c.   Incubation: 37℃, 18 hours

40. Antibiotic Sensitivity Test  How to explain the results?  How to avoid misleading of clinicians?  How to standardize the test?

41. Reading and evaluation of sensitivity test 1、Physical and chemical profile of the medicine 2、Metabolic process 3、Identification of sensitivity & resistance 4、Q.C. 5、Who is responsible for those work?