Anti-bacteria MedicineAnti-bacteria Medicine

Anti-bacteria medicineAnti-bacteria medicine

Antibiotics: The substance derived Antibiotics: The substance derived from fungi and bacteria which can from fungi and bacteria which can selectively kill or inhibit bacteria selectively kill or inhibit bacteria growthgrowth

Anti-bacteria medicine: Chemically Anti-bacteria medicine: Chemically synthesized medicine which can synthesized medicine which can selectively kill or inhibit bacteria selectively kill or inhibit bacteria growthgrowth

Antibacteria medicineAntibacteria medicine

SulfonamideSulfonamide QuilononesQuilonones othersothers

Antibiotics and drugs Antibiotics and drugs

targeting nucleic acid targeting nucleic acid

biosynthesis and biosynthesis and

functionsfunctions

Antibiotics and drugs targeting Antibiotics and drugs targeting nucleic acid biosynthesis and nucleic acid biosynthesis and functionsfunctions

1. Sulphonamides & Trimethoprim (TMP)1. Sulphonamides & Trimethoprim (TMP)

PABA false structurePABA false structure

Inhibition of Dihydrofolate reductaseInhibition of Dihydrofolate reductase

Dihydrofolate Dihydrofolate tetrahydrofolate tetrahydrofolate

2. Quinolones Bacterial topoisomerase II- Gyrase

Nalidixic acidNalidixic acid

OfloxacinOfloxacin

CiprofloxacinCiprofloxacin

Antibiotics and drugs targeting Antibiotics and drugs targeting nucleic acid biosynthesis and nucleic acid biosynthesis and functionsfunctions

3. Rifampicin (from rifamycin)3. Rifampicin (from rifamycin)

subunit of DNA-primed RNA polymeassubunit of DNA-primed RNA polymeas

ee

Antibiotics and drugs targeting Antibiotics and drugs targeting nucleic acid biosynthesis and nucleic acid biosynthesis and functionsfunctions

! Rifampicin must be given by ! Rifampicin must be given by

a “cocktail” of drugs.a “cocktail” of drugs.

Antibiotics and drugs targeting Antibiotics and drugs targeting nucleic acid biosynthesis and nucleic acid biosynthesis and functionsfunctions

Problem of antibiotics Problem of antibiotics

which inhibit which inhibit

protein synthesis protein synthesis

Antibiotics: From isolation of stAntibiotics: From isolation of strain to clinical applicationrain to clinical application

Selection of a potential productSelection of a potential product

11 、、 efficacyefficacy22 、、 metabolic characterizationmetabolic characterization33 、、 toxicity and adverse effecttoxicity and adverse effect44 、、 Potentiality of industrial productiPotentiality of industrial producti

onon

Antibiotics: from strain isolation Antibiotics: from strain isolation to clinical applicationto clinical application

Semi-synthesis: the most Semi-synthesis: the most popular approach of popular approach of production production

Marketing potentialityMarketing potentiality Life-span of marketing and its Life-span of marketing and its

impactimpact

% ö

verl

evar

e

Penicillin

Obehandlade

Dagar

Penicillin increased the chance of survival from 10% to 90%

Patients withpneumonia 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 What is Antibiotic Resistance?Resistance?

Bacterial Resistance Bacterial Resistance to Antibiotics to Antibiotics

Enzymes secreted (exo-enzyme)Enzymes secreted (exo-enzyme) Enzymes not secreted (endo-enzymes)Enzymes not secreted (endo-enzymes) Deletion of target molecules Deletion of target molecules Change in cell permeabilityChange in cell permeability Change in target molecule affinityChange in target molecule affinity Speed-up of synthesis and metabolismSpeed-up of synthesis and metabolism OthersOthers

Mechanism of Mechanism of resistanceresistance

Selection pressure ( not only in Selection pressure ( not only in health institutions)health institutions)

Genetic recombination Genetic recombination ( especially conjugation mediated ( especially conjugation mediated by plasmid)by plasmid)

Improper prescription of antibioticImproper prescription of antibioticss

Antibiotic prescription for non-Antibiotic prescription for non-bacterial infectionbacterial infection

Prophylaxis application of antibioticsProphylaxis application of antibiotics Local application of antibioticsLocal application of antibiotics Over use of wide-spectrum Over use of wide-spectrum

antibioticsantibiotics Long-term use of antibioticsLong-term use of antibiotics Antibiotic abuse in agriculture Antibiotic abuse in agriculture

productionproduction

Hip replacement

Organ transplants

Cancer chemotherapy

Care of preterm babies

Modern Medicine Is Not Possible Without Effective Antibiotics

The survival of the The survival of the fittestfittest

Horisontal spread of resisHorisontal spread of resistance genestance genes

Spread of resistance between species

Barrier to the development of Barrier to the development of new antibioticsnew antibiotics

Short marketing life of the product becauShort marketing life of the product because of resistance se of resistance

Difficult R&DDifficult R&D 11 、、 qualified strainqualified strain 22 、、 resources to support R&Dresources to support R&D 33 、、 long term research and translationlong term research and translation Adverse reactionsAdverse reactions Expense for health careExpense for health care

The outcome of resistance The outcome of resistance development development (From the view point of bacteria (From the view point of bacteria cells)cells)

Uneconomic state of cell metabolismUneconomic state of cell metabolism

Slow-down of proliferationSlow-down of proliferation

deletion of some pathogenic abilitiesdeletion of some pathogenic abilities

Avoiding harms from drugsAvoiding harms from drugs

Antibiotic sensitivity Antibiotic sensitivity test test

MIC & MBCMIC & MBC

Broth dilutionBroth dilution

Agar dilutionAgar dilution

Disk diffusionDisk diffusion

Standard requirementsStandard requirements

Antibiotic sensitivity Antibiotic sensitivity testtest

Standard requirements:Standard requirements:

a.   Depth: 4mma.   Depth: 4mm

b.  Inoculates: 10b.  Inoculates: 105 5 cell/mlcell/ml

c.   Incubation: 37℃, 18 c.   Incubation: 37℃, 18

hourshours

Antibiotic Sensitivity Antibiotic Sensitivity TestTest

How to explain the results? How to explain the results?

How to avoid misleading of cliniciaHow to avoid misleading of clinicians?ns?

How to standardize the test? How to standardize the test?

Reading and evaluation of Reading and evaluation of sensitivity testsensitivity test

11 、、 Physical and chemical profile of thPhysical and chemical profile of the medicinee medicine

22 、、 Metabolic processMetabolic process33 、、 Identification of sensitivity & resiIdentification of sensitivity & resi

stance stance 44 、、 Q.C.Q.C.55 、、 Who is responsible for those work?Who is responsible for those work?