Antimicrobial Drugs (the stuff Dr. Figueroa didn

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Antimicrobial Drugs(the stuff Dr. Figueroa
didnt tell you about in MIP)

• Jeffery A. Hobden, Ph.D.

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Wonder Drugs

• Decreased morbidity and mortality in US after
  WWII from infectious diseases
• Made practical some areas of medicine
• Cancer chemotherapy
• Gut surgery
• Increased productivity in agriculture

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Antibiotics - Exploited

• In 2007, two antibiotics were in the top 20 drugs
  prescribed in the US
• Amoxicillin 34,801,000
• Azithromycin 23,782,000
• In 2000, 24 million pounds of antibiotics were
  used in agriculture (chickens, pigs, cattle, etc)
  vs. 3 million pounds used to treat sick humans
• Unrestricted access

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Top 20 Prescribed Drugs
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Tainted Seafood

• Chinese seafood tested between 10/06 and 05/07
  were repeatedly positive for
• Nitrofuran
• Malachite green
• Fluoroquinolones
• Shipments banned from entering US
• Buy only local seafood!

Alabama officials hold a press conference
Drugs in your seafood are bad, MKay?
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The Consequences
That which does not kill us makes us stronger.
- Friedrich Nietzsche
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Cant we just get more?

• Screening natural or synthetic compounds for
  antibacterial activity
• Preclinical studies (animals)
• Safety (what is safe for animals may not be true
  for humans)
• Efficacy (pharmacological parameters are
  different in animals)

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Wait theres more

• Clinical studies (humans)
• Phase 1 short term studies in small number of
  healthy humans or patients with target disease,
  to determine metabolism and basic pharmacologic
  and toxicological properties of antibiotic
• Phase 2 first controlled clinical studies to
  assess the effectiveness of the antibiotic and to
  determine short-term side effects and risks.
• Phase 3 expanded controlled and uncontrolled
  clinical studies to gather data regarding benefit
  risk relationship.
• Phase 4 marketing!

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Is it any wonder?

• Antibiotics are big business for pharm
• Freebies
• Advertising
• Sponsorships
• Not as profitable as drugs for erectile
  dysfunction, cholesterol control, anxiety
  attacks, etc.

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After MIP, what else is there to know about
antibiotics?

• Whats the origin of that antibiotic?
• Whats special about its chemistry?
• What happens to it after its in my body?
• Will it kill or maim me if I take it?

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Classification of Antibioticsby Mechanism of
Action

• Inhibition of cell wall synthesis
• Beta-lactam drugs
• Penicillins
• Cephalosporins
• Carbapenems
• The others
• Cycloserine
• Vancomycin
• bacitracin

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Classification of Antibioticsby Mechanism of
Action

• Disruption of cell membranes
• Polymyxin
• Polyenes (anti-fungal agents)

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Classification of Antibioticsby Mechanism of
Action

• Inhibition of protein synthesis
• Reversible inhibition (bacteristatic)
• Chloramphenicol
• The tetracyclines
• The macrolides (erythromycin)
• Clindamycin
• Streptogramins
• Linezolid
• Irreversible the bactericidal aminoglycosides

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Susceptibility and Resistance

• In vitro values are guides, not rules
• In vivo, bug is resistant if cidal concentrations
  are toxic to the host
• Achievable serum concentrations are what
  determine susceptibility or resistance to drug
• Low pH, high protein concentrations, anoxia
• Pharmacological parameters of drugs (serum versus
  other bodily fluids)

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Bacterial Mechanisms of Resistance

• Prevent antibiotic from reaching its target
• Destroy or inactivate antibiotic before it
  reaches target
• Alter target

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Choosing the right antibiotic is it really
needed?

• Nature of the illness is it a bacterial
  infection or something else?
• Presumptive diagnosis (based on history and
  clinical symptoms) says yes!
• Empiric therapy broad spectrum drug
• Specific therapy narrow spectrum

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Choosing the right antibiotic pharmacokinetic
considerations.

• Location of infection
• Some antibiotics may or may not reach therapeutic
  concentrations in certain bodily fluids (ex. CSF
  and urine)
• Degree to which antibiotic binds serum proteins
• Excessive binding will affect passive diffusion
  of antibiotic from serum to tissue

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Choosing the right antibiotic host factors.

• Status of host immune system (cidal vs. static)
• Local environment of infected site (pus, foreign
  bodies, etc)
• Age (organ function in newborns and elderly)
• Inherited metabolic disorder
• Pregnancy (fetal or neonatal development)

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Choosing the right antibiotic host factors.

• drug allergies
• Rashes
• Anaphylaxis
• Co-morbid conditions are aggravated by some
  antibiotics
• Seizures
• Blood disorders

SJS Syndrome
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First up.

• The sulfonamides
• The quinolones
• The beta-lactams
• Penicillins
• Cephalosporins
• Carbapenems

Looking a-head.