Antibiotics by yaoyufang

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									Antibiotics
                  Overview
• If bacteria make it past our immune system
  and start reproducing inside our bodies, they
  cause disease.
• Certain bacteria produce chemicals that
  damage or disable parts of our bodies.
• Antibiotics work to kill bacteria.Antibiotics are
  specific to certain bacteria and disrupt their
  function.
            What is an Antibiotic?
• An antibiotic is a selective poison.
• It has been chosen so that it will kill the desired
  bacteria, but not the cells in your body. Each
  different type of antibiotic affects different bacteria
  in different ways.
• For example, an antibiotic might inhibit a bacteria's
  ability to turn glucose into energy, or the bacteria's
  ability to construct its cell wall. Therefore the
  bacteria dies instead of reproducing.
                  History
• Although for centuries preparations derived
  from living matter were applied to wounds to
  destroy infection, the fact that a
  microorganism is capable of destroying one
  of another species was not established until
  the latter half of the 19th cent. when Pasteur
  noted the antagonistic effect of other bacteria
  on the anthrax organism and pointed out that
  this action might be put to therapeutic use.
                     History
• Meanwhile the German chemist Paul Ehrlich
  developed the idea of selective toxicity: that
  certain chemicals that would be toxic to some
  organisms, e.g., infectious bacteria, could be
  killed but not other organisms, e.g., humans.
• In 1928, Sir Alexander Fleming, a Scottish
  biologist, observed that Penicillium notatum, a
  common mold, had destroyed staphylococcus
  bacteria in culture.
                       History
• In 1939 the American microbiologist René Dubos
  demonstrated that a soil bacterium was capable of
  decomposing the starchlike capsule of the pneumococcus
  bacterium, without which the pneumococcus is harmless
  and does not cause pneumonia. Dubos then found in the
  soil a microbe, Bacillus brevis, from which he obtained a
  product, tyrothricin, that was highly toxic to a wide
  range of bacteria. Tyrothricin, a mixture of the two
  peptides gramicidin and tyrocidine, was also found to be
  toxic to red blood and reproductive cells in humans but
  could be used to good effect when applied as an
  ointment on body surfaces.
           History continued
• Dubos then found in the soil a microbe,
  Bacillus brevis, from which he obtained a
  product, tyrothricin, that was highly toxic to
  a wide range of bacteria. Tyrothricin, a
  mixture of the two peptides gramicidin and
  tyrocidine, was also found to be toxic to red
  blood and reproductive cells in humans but
  could be used to good effect when applied
  as an ointment on body surfaces.
                  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
 produded by bacteria

Many are now chemically synthesized
            Classification
Antibiotics can be classified in several
 ways.
1. Spectrum
2. Bactericidal or bacteriostatic
3. Modes of action
4. Chemical structure



-
            Spectrum
Broad
They target a number of bacteria or they
  are specific to one type
Used for diseases like meningitis
e.g. amoxicillin
Narrow
Target only a group of bacteria
Good for preventing antibiotic resistance
Eg. vancomycin
          Classification
1. Bactericidal or bacteriostatic


Bactericidal – kills bacteria


Bacteriostatic – stops bacterial growth



-
       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
•   Macrolides
•   Fluoroquinolones
•   Tetracyclines
•   Aminoglycosides
      Administration and Side
             Effects
• Antibiotics are either injected, given orally, or
  applied to the skin in ointment form. Many, while
  potent anti-infective agents, also cause toxic side
  effects. Some, like penicillin, are highly allergenic
  and can cause skin rashes, shock, and other
  manifestations of allergic sensitivity. Others, such
  as the tetracyclines, cause major changes in the
  intestinal bacterial population and can result in
  superinfection by fungi and other microorganisms.
  Production of Antibiotics
• The mass production of antibiotics
  began during World War II with
  streptomycin and penicillin. Now most
  antibiotics are produced by staged
  fermentations in which strains of
  microorganisms producing high yields
  are grown under optimum conditions in
  nutrient media in fermentation tanks
  holding several thousand gallons.
          Production of Antibiotics
• The mold is strained out of the fermentation broth, and
  then the antibiotic is removed from the broth by
  filtration, precipitation, and other separation methods.
  In some cases new antibiotics are laboratory
  synthesized, while many antibiotics are produced by
  chemically modifying natural substances; many such
  derivatives are more effective than the natural
  substances against infecting organisms or are better
  absorbed by the body, e.g., some semisynthetic
  penicillins are effective against bacteria resistant to
  the parent substance.
   Antimicrobial Resistance

• Relative or complete lack of effect
  of antimicrobial against a
  previously susceptible microbe
• Increase in MIC
       Mechanisms of Antibiotic
             Resistance

•   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 4 states in 18 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
•   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

								
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