Patrick

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Patrick An Introduction to Medicinal Chemistry
3/e Chapter 16 ANTIBACTERIAL AGENTS Part 3
Other lactams
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Newer b-Lactam Antibiotics
Thienamycin (Merck 1976)(from Streptomyces
cattleya)

• Potent and wide range of activity vs Gram ve and
  Gram -ve bacteria
• Active vs. Pseudomonas aeruginosa
• Low toxicity
• High resistance to b-lactamases
• Poor stability in solution (ten times less stable
  than Pen G)

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Newer b-Lactam Antibiotics
Thienamycin analogues used in the clinic
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Newer b-Lactam Antibiotics
Nocardicins (Fujisawa 1975)

• Monocyclic b-lactam ring - monobactams
• Moderately active in vitro vs narrow group of
  Gram -ve bacteria
• Active vs. Pseusomonas aeruginosa
• Inactive vs. Gram ve bacteria
• Different spectrum of activity from penicillins
• Thought to operate by a different mechanism from
  penicillins
• Low toxicity

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Newer b-Lactam Antibiotics
Clinically useful monobactam

• Administered by intravenous injection
• Can be used for patients with allergies to
  penicillins
• and cephalosporins
• No activity vs. Gram ve or anaerobic bacteria
• Active vs. Gram -ve aerobic bacteria

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b-Lactamase Inhibitors
Clavulanic acid (Beechams 1976)(from Streptomyces
clavuligerus)

• Weak, unimportant antibacterial activity
• Powerful irreversible inhibitor of b-lactamases -
  suicide substrate
• Used as a sentry drug for ampicillin
• Augmentin ampicillin clavulanic acid
• Allows less ampicillin per dose and an increased
  activity spectrum
• Timentin ticarcillin clavulanic acid

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b-Lactamase Inhibitors
Clavulanic acid - mechanism of action
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b-Lactamase Inhibitors
Penicillanic acid sulfone derivatives

• Suicide substrates for b-lactamase enzymes
• Sulbactam has a broader spectrum of activity vs
  b-lactamases than clavulanic acid, but is less
  potent
• Unasyn ampicillin sulbactam
• Tazobactam has a broader spectrum of activity vs
  b-lactamases than clavulanic acid, and has
  similar potency
• Tazocin or Zosyn piperacillin tazobactam