1. β-LACTAM ANTIBIOTICS
THIENAMYCIN
MONOBACTAMS
β-LACTAM INHIBITORS

2. 1. Thienamycin Merck 1976 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)

3. 1. Thienamycin Imipenem Meropenem Ertapenem(2002)
Thienamycin analogues used in the clinic
Imipenem
Ertapenem(2002)
Meropenem

4. 2. Monobactams Nocardicin A 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

5. 2. Monobactams Aztreonam 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

6. 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

7. 3. b-Lactamase Inhibitors
Clavulanic acid - mechanism of action O H N 2 1 2 N H 3 4 5

8. 3. b-Lactamase Inhibitors
Penicillanic acid sulfone derivatives
Sulbactam
Tazobactam
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

9. COMPULSORY READING FROM TEXTBOOK – WILSON AND GISVOLD
PAGES – 278
EXAMPLES: CLAVULANATE POTASSIUM, SULBACTAM, TAZOBACTAM, THIENAMYCIN, MEROPENEM [PAGES 274 – 278]

10. COMPULSORY READING FROM TEXTBOOK – PATRICK
THE ENTIRE SECTION ON b – LACTAMASE INHIBITORS AND ANTIBIOTICS IN CHAPTER 19