Transcript Antibiotics

Anti-bacteria Medicine
Anti-bacteria medicine
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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
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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
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Nalidixic acid
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Ofloxacin
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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
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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
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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
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Selection pressure ( not only in health
institutions)
Genetic recombination ( especially
conjugation mediated by plasmid)
Improper prescription of
antibiotics
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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
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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
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Adverse reactions
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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?