1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 84 Drugs That Weaken the Bacterial Cell Wall I: Penicillins

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Penicillins  Active against a variety of bacteria  Direct toxicity: low  Principal adverse effect: allergic reaction  Beta-lactam ring in their structure  Beta-lactam family: also includes cephalosporins, aztreonam, imipenem, meropenem, and ertapenem

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Penicillins  Mechanism of action  Weaken the cell wall, causing bacteria to take up excessive water and rupture  Active only against bacteria that are undergoing growth and division  Bactericidal  Bacterial resistance Inability of penicillins to reach their target Inability of penicillins to reach their target Inactivation of penicillins by bacterial enzymes Inactivation of penicillins by bacterial enzymes

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 Mechanisms of Bacterial Resistance  Three factors  Inability of penicillins to reach their targets  Inactivation of penicillins by bacterial enzymes  Production of penicillin-binding proteins (PBPs) that have a low affinity for penicillins

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Cell Envelope  Gram-negative cell envelope  Three layers  Thin cell wall and an additional outer membrane that is hard to penetrate  Gram-positive cell envelope  Only two layers  Relatively thick cell wall that is easily penetrated

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.6 Penicillinases  Beta-lactamases  Enzymes that render penicillin inactive  Bacteria can produce a large variety of these enzymes specific for penicillins (and other beta-lactam antibiotics)

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Classification of Penicillins  Narrow-spectrum penicillins  Pencillinase-sensitive  Narrow-spectrum penicillins  Pencillinase-resistant  Broad-spectrum penicillins  Extended-spectrum penicillins

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Penicillin G (Benzylpenicillin)  Bactericidal to numerous gram-positive and some gram-negative organisms  Adverse effects  Least toxic of all antibiotics  Penicillins are the most common cause of drug allergy

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 Penicillin Allergy  Development of penicillin allergy  Skin tests for penicillin allergy  Management of patients with a history of penicillin allergy  Assess for penicillin allergy in each patient who will be receiving penicillin  If history of mild reaction, consider cephalosporin  If history of anaphylaxis, avoid administration of penicillin or cephalosporins

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Penicillin Allergy  Types  Immediate (reaction in 2–30 minutes)  Accelerated (reaction in 1–72 hours)  Late (reaction takes days or weeks to develop)  Anaphylaxis  Laryngeal edema  Bronchoconstriction  Severe hypotension

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 Penicillin Allergy  Treatment  Epinephrine  Respiratory support  Prevention: skin testing

12. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Drug Interactions  Aminoglycosides  Penicillin V

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Penicillinase-Resistant Penicillins  Available in the United States  Nafcillin  Oxacillin  Dicloxacillin  MRSA: methicillin-resistant Staphylococcus aureus

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.14 Broad-Spectrum Penicillins  Broad-spectrum penicillins (aminopenicillins)  Ampicillin (Principen)  Amoxicillin (Amoxil, DisperMox, Moxatag, Trimox)  Adverse effects  Rash  Diarrhea

15. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.15 Extended-Spectrum Penicillins  Extended-spectrum penicillins (antipseudomonal penicillins)  Piperacillin Broad-spectrum, but penicillinase-sensitive Broad-spectrum, but penicillinase-sensitive

16. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 Penicillin Combinations  Beta-lactamase inhibitors  Clavulanic acid, tazobactam, sulbactam  Extends antimicrobial spectrum when combined with penicillinase-sensitive antibiotics  Ampicillin/sulbactam (Unasyn)  Amoxicillin/clavulanic acid (Augmentin)  Ticarcillin/clavulanic acid (Timentin)  Piperacillin/tazobactam (Zosyn)