Anti-bacteria Medicine

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

Antibacteria medicine Antibacteria medicine Sulfonamide Sulfonamide Quilonones Quilonones others others

Antibiotics and drugs targeting nucleic acid biosynthesis and functions

1. Sulphonamides & Trimethoprim (TMP) PABA false structure Inhibition of Dihydrofolate reductase Inhibition of Dihydrofolate reductase Dihydrofolate  tetrahydrofolate Dihydrofolate  tetrahydrofolate

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

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

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

Problem of antibiotics which inhibit protein synthesis

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

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

% överlevare Penicillin Obehandlade Dagar Penicillin increased the chance of survival from 10% to 90% Patients with pneumonia and bacteria in blood

“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

The Global Challenge Antibiotics have saved millions of lives Antibiotics are rapidly losing their effect The Global Challenge Antibiotics have saved millions of lives Antibiotics are rapidly losing their effect

What is Antibiotic Resistance?

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

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

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

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

The survival of the fittest The survival of the fittest

Horisontal spread of resistance genes Spread of resistance between species

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

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

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

Antibiotic sensitivity test Standard requirements: a. Depth: 4mm b. Inoculates: 10 5 cell/ml c. Incubation: 37 ℃, 18 hours

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

Reading and evaluation of sensitivity test 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?