Ch. 20

1
Ch. 20

• Chemotherapeutic agents - chemicals used to treat
  bacterial and fungal infections

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1. Antibiotics

• Chemicals made by one microorganism which inhibit
  or kill other microorganisms

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1. Antibiotics

• Streptomyces - many antibiotics
• Bacillus -bacitracin
• Eupenicillium - penicillin

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2. Synthetic drugs

• Chemicals made in the laboratory which inhibit or
  kill microorganisms

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2. Synthetic drugs

• Chemical made in the laboratory which inhibit or
  kill microorganisms
• sulfa drugs

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Criteria for choosing an antibiotic or synthetic
drug

• 1. Selective toxicity - effective against the
  microorganism but not the person
• 2. No hypersensitivity (allergy)
• 3. Broad spectrum ? (effective against both Gram
  and Gram -)
• 4. Not destroy the normal flora

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Candida albicans - thrush and vaginitis
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Criteria for choosing an antibiotic or synthetic
drug

• 1. Selective toxicity - effective against the
  microorganism but not the person
• 2. No hypersensitivity (allergy)
• 3. Broad spectrum ? (effective against both Gram
  and Gram -)
• 4. Not destroy the normal flora
• not have other side effects
• 5. No resistance

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Mechanisms of action pg. 534

• 1.

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Mechanisms of action pg. 534

• 1.

Peptidoglycan is weakened - cell bursts
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Penicillin treated cells
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Mechanisms of action pg. 534

• 1.

Peptidoglycan - cell bursts selectively toxic -
humans do not have peptidoglycan so are not
affected
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Natural penicillins pg. 539
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Natural penicillins pg. 539

• Effective mostly against Gram
• inactivated by Beta - lactamases (penicillinase)

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Beta lactamases (penicillinase) pg. 540
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Semi-synthetic penicllins
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Semi-synthetic penicillins

• Broad spectrum -ampicillin
• resistant to beta-lactamases - methicillin

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MRSA

• Methicillin resistant Staphylococcus aureus
• only antibiotic that will be active is -
  vancomycin
• VREvancomycin resistant enterococci

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Mechanisms of action pg. 534

• 2.

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Inhibition of protein synthesis

• Antibiotic combines with 50 S or 30 S portion of
  the bacterial riibosome
• inhibits translation
• mostly selectively toxic - humans have 80S
  ribosomes (subunits of 60S and 40S)
• humans have mitochondria with 70S ribosomes so it
  will inhibit mitochondrial protein synthesis

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Pg. 535
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Pg. 535
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Mechanisms of action pg. 534
3.
Most are not selectively toxic
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Mechanisms of action
4.
Anti-bacterial
Nystatin, amphotericin B -anti-fungals
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Cell lysis
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Mechanisms of action
4.
Anti-bacterial
Nystatin, amphotericin B -anti-fungals
Not selectively toxic - humans have a similar
membrane structure but with some differences
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Mechanisms of action
5. Metabolic inhibitors
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Mechanisms of action
5. Metabolic inhibitors
Most are selectively toxic
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Drug resistance

• Mutations
• R factor transfers
• transposons

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Mechanisms

• 1. Bacterial enzymes degrade or chemically
  inactivate antibiotic/drug ex. Beta lactamases

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Mechanisms

• 1. Bacterial enzymes degrade or chemically
  inactivate antibiotic/drug ex. Beta lactamases
• 2. Bacteria alter or replace the molecules that
  are targets of the antibiotic/drug ex. Altered
  ribosomes
• 3. Bacteria prevent entry or pump out the
  antibiotic/drug ex. Gram - cell wall

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To minimize drug resistance

• 1. Use antibiotics only when necessary
• bacterial infections only - no viral infections
• use specific antibiotic for that bacterium
• no antibiotics in meat
• 2. Use dose to control the microorganism as
  quickly as possible
• single injection or 10-14 days by mouth
• use the full dose
• no long-term antibiotic therapy

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To minimize drug resistance

• 3. Isolate the bacterium from the patient and use
  the Kirby Bauer method to determine its
  susceptibilities
• 4. Use 2 or more antibiotics at once Ex.
  Tuberculosis
• synergism work together
• antagonism work against each other

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To minimize drug resistance

• 5. Use a different antibiotic when resistance
  develops

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Tests to evaluate antibiotics, synthetic drugs

• Diffusion methods
• Kirby Bauer (disk diffusion)

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Kirby Bauer pg. 549
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Tests to evaluate antibiotics, synthetic drugs

• Diffusion methods
• Kirby Bauer (disk diffusion)
• E test

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E test pg. 550
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Tests to evaluate antibiotics, synthetic drugs

• Diffusion methods
• Kirby Bauer (disk diffusion)
• E test
• MIC (minimal inhibitory concentration) lowest
  concentration of the drug which inhibits growth

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Tests to evaluate antibiotics, synthetic drugs

• Diffusion methods
• Kirby Bauer (disk diffusion)
• E test
• MIC (minimal inhibitory concentration)
• Broth dilution
• tube dilution
• microdilution plate

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Microdilution plate pg. 550
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Dilution techniques

• Prepare different dilutions of the antibiotic/drug

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Microdilution plate pg. 550
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Dilution techniques

• Prepare different dilutions of the
  antibiotic/drug
• Add bacteria and incubate
• Record which dilutions show growth

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Microdilution plate pg. 550
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Diluton techniques

• Prepare different dilutions of the
  antibiotic/drug
• Add bacteria and incubate
• Record which dilutions show growth
• Determine MIC (minimal inhibitory concentration)
  lowest concentration at which growth was
  inhibited

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Microdilution plate pg. 550
48
Diluton techniques

• Prepare different dilutions of the
  antibiotic/drug
• Add bacteria and incubate
• Record which dilutions show growth
• Determine MIC (minimal inhibitory concentration)
  lowest concentration at which growth was
  inhibited
• 3-4 x this concentration in the blood

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Dilution tests

• MBC minimal bacteriocidal concentration
• subculture the previous tubes
• note growth after incubation
• MBC lowest concentration in which growth was
  inhibited in subculture

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Microdilution plate pg. 550
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Dilution tests

• MBC minimal bacteriocidal concentration
• subculture the previous tubes
• note growth after incubation
• MBC lowest concentration in which growth was
  inhibited in subculture
• 3-4 x this concentration in the bloodstream