Anti-bacteria Medicine 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 Antibacteria medicine Sulfonamide Quilonones others Antibiotics and drugs targeting nucleic acid biosynthesis and functions Antibiotics and drugs targeting nucleic acid biosynthesis and functions 1. Sulphonamides & Trimethoprim (TMP) PABA false structure Inhibition of Dihydrofolate reductase Dihydrofolate tetrahydrofolate Antibiotics and drugs targeting nucleic acid biosynthesis and functions 2. Quinolones Nalidixic acid Ofloxacin Ciprofloxacin Bacterial topoisomerase II- Gyrase 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. Problem of antibiotics which inhibit protein synthesis 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 Antibiotics: from strain isolation to clinical application Semi-synthesis: the most popular approach of production Marketing potentiality Life-span of marketing and its impact Patients with pneumonia and bacteria in blood Penicillin increased the chance of survival from 10% to 90% % överlevare Penicillin Obehandlade Dagar “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 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) Genetic recombination ( especially conjugation mediated by plasmid) 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 Modern Medicine Is Not Possible Without Effective Antibiotics Hip replacement Organ transplants Cancer chemotherapy Care of preterm babies The survival of the fittest Horisontal spread of resistance genes Spread of resistance between species 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 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: 105 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 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?