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ß-LACTAM ANTIBIOTICS THIENAMYCIN MONOBACTAMS ß-LA
CTAM INHIBITORS
2
1. Thienamycin

• Isolated 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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1. Thienamycin
Thienamycin analogues used in the clinic
4
2. Monobactams
Nocardicins (Fujisawa 1975)

• Monocyclic b-lactam ring
• 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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2. Monobactams
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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3. b-Lactamase Inhibitors
Clavulanic acid (Beechams 1976)

• Isolated 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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3. b-Lactamase Inhibitors
Clavulanic acid - mechanism of action
8
3. 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

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COMPULSORY READING FROM TEXTBOOK WILSON AND
GISVOLD

• PAGES - 274 278
• EXAMPLES CLAVULANATE POTASSIUM, SULBACTAM,
  TAZOBACTAM, THIENAMYCIN, MEROPENEM PAGES 274
  278

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COMPULSORY READING FROM TEXTBOOK PATRICK

• THE ENTIRE SECTION ON b LACTAMASE INHIBITORS
  AND ANTIBIOTICS IN CHAPTER 19