Transcript Antibiotics

Antibiotics
Definition
• any of a variety of substances, usually
obtained from microorganisms, that inhibit
the growth of or destroy certain other
microorganisms.
History
• Pasteur observed that other bacteria had
antagonistic effects on the bacteria
responsible for anthrax
• German chemist Paul Ehrlich developed the
idea of selective toxicity: that certain
chemicals that would be toxic to some
organisms
History cont’d
• In 1928, Sir Alexander Fleming, a Scottish
biologist, observed that Penicillium notatum, a
common mold, had destroyed staphylococcus
bacteria in culture.
History
• 1939, microbiologist René Dubos – found that Bacillus
brevis from soil inhibited pneumococcus growth – with
tyrothricin (but toxic to human cells)
• Penicillin was finally isolated in 1939, and in 1944
Selman Waksman and Albert Schatz, American
microbiologists, isolated streptomycin and a number of
other antibiotics from Streptomyces griseus.
History
• Penicillin was finally isolated in 1939, and
in 1944 Selman Waksman and Albert
Schatz, American microbiologists, isolated
streptomycin and a number of other
antibiotics from Streptomyces griseus.
Antibiotics today
The antibiotics we take today are still
produced by bacteria in large fermentation
tanks….
Some are synthetic….but much more
expensive
Classification
Antibiotics can be classified in several
ways, for example:
1. Spectrum
2. Modes of action
3. Chemical structure
-
Spectrum
Broad
They target a range of bacteria (gram
+ve and –ve)
Uses:
- If pathogen is not identified
- For superinfections
Examples:
Amoxicillin, tetracycline, streptomycin
Antibiotic spectrum
Narrow
- Target only a group of bacteria
usually once the pathogen is
identified
- Good for preventing antibiotic
resistance
Eg. vancomycin
Classification
Modes of action
• Some antibiotics attack the cell
wall; some disrupt the cell
membrane; and others inhibit the
synthesis of nucleic acids and
proteins.
Penicillin
• All penicillin like antibiotics inhibit synthesis of
peptidoglycan, an essential part of the cell wall.
They do not interfere with the synthesis of
other intracellular components.
• The continuing buildup of materials inside the
cell exerts ever greater pressure on the
membrane, which is no longer properly
supported by peptidoglycan.
• The membrane gives way, the cell contents
leak out, and the bacterium dies. These
antibiotics do not affect human cells because
human cells do not have cell walls.
Mechanisms of Action
• Many antibiotics operate by inhibiting the
synthesis of various intracellular bacterial
molecules, including DNA, RNA, ribosomes, and
proteins. The synthetic sulfonamides are
among the antibiotics that indirectly interfere
with nucleic acid synthesis. Some antibacterials
affect the assembly of messenger RNA, thus
causing its genetic message to be garbled.
When these faulty messages are translated, the
protein products are nonfunctional.
Classification
by chemical structure
• Beta-Lactams
– Penicillins
– Cephalosporins
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Macrolides
Fluoroquinolones
Tetracyclines
Aminoglycosides
Administration and Side
Effects
• Administration
Injected, given orally or topically-applied
Side effects
- Allergies
- Skin rashes
- Fever, nausea, diarrhea
- Changes in intestinal bacteria
Production of Antibiotics
• mass production during World WarII
with streptomycin and penicillin
• now antibiotics are produced by
fermentations with high-yielding
microorganisms producing high yields
are grown under optimum conditions
Production of Antibiotics
• Some new antibiotics are laboratory synthesized,
while many antibiotics are produced by chemically
modifying natural substances
• some semi-synthetic penicillins are effective against
bacteria resistant to the parent substance.
• E.g. amoxycillin
Antimicrobial Resistance
• Relative or complete lack of effect
of antimicrobial against a
previously susceptible microbe
Mechanisms of Antibiotic
Resistance
•
•
•
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Enzymatic destruction of drug
Prevention of penetration of drug
Alteration of drug's target site
Rapid ejection of the drug
Antibiotic Selection for
Resistant Bacteria
What Factors Promote
Antimicrobial Resistance?
• Exposure to sub-optimal levels of
antimicrobial
• Exposure to microbes carrying
resistance genes
Inappropriate Antimicrobial
Use
• Prescription not taken correctly
• Antibiotics for viral infections
• Antibiotics sold without medical
supervision
• Spread of resistant microbes in
hospitals due to lack of hygiene
Inappropriate Antimicrobial
Use
• Lack of quality control in manufacture or
outdated antimicrobial
• Inadequate surveillance or defective
susceptibility assays
• Poverty or war
• Use of antibiotics in foods
Antibiotics in Foods
• Antibiotics are used in animal feeds and
sprayed on plants to prevent infection and
promote growth
• Multi drug-resistant Salmonella typhi has
been found in people who ate beef fed
antibiotics
Consequences of
Antimicrobial Resistance
• Infections
resistant to
available
antibiotics
• Increased cost
of treatment
Multi-Drug Resistant TB
MRSA “mer-sah”
• Methicillin-Resistant
Staphylococcus aureus
• Most frequent nosocomial
(hospital-acquired) pathogen
• Usually resistant to several other
antibiotics
Vancomycin Resistant Enterococci
Vancomycin Use USA
Proposals to Combat
Antimicrobial Resistance
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Speed development of new antibiotics
Track resistance data nationwide
Restrict antimicrobial use
Direct observed dosing (TB)
Proposals to Combat
Antimicrobial Resistance
• Use more narrow spectrum
antibiotics
• Use antimicrobial cocktails