Chapter 84
Drugs That Weaken the Bacterial
Cell Wall I: Penicillins
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Penicillins
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Penicillins
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Mechanism of action
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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
• Inactivation of penicillins by bacterial enzymes
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Mechanisms of Bacterial Resistance
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Three factors
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Cell Envelope
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Gram-negative cell envelope
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Three layers
Thin cell wall and an additional outer membrane
that is hard to penetrate
Gram-positive cell envelope
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Only two layers
Relatively thick cell wall that is easily penetrated
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Penicillinases
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Beta-lactamases
Enzymes that render penicillin inactive
Bacteria can produce a large variety of these
enzymes specific for penicillins (and other
beta-lactam antibiotics)
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Classification of Penicillins
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Narrow-spectrum penicillins
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Narrow-spectrum penicillins
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Pencillinase-sensitive
Pencillinase-resistant
Broad-spectrum penicillins
Extended-spectrum penicillins
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Penicillin G (Benzylpenicillin)
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Bactericidal to numerous gram-positive and
some gram-negative organisms
Adverse effects
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Least toxic of all antibiotics
Penicillins are the most common cause of drug
allergy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Penicillin Allergy
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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
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If history of mild reaction, consider cephalosporin
If history of anaphylaxis, avoid administration of
penicillin or cephalosporins
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Penicillin Allergy
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Types
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Immediate (reaction in 2–30 minutes)
Accelerated (reaction in 1–72 hours)
Late (reaction takes days or weeks to develop)
Anaphylaxis
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Laryngeal edema
Bronchoconstriction
Severe hypotension
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Penicillin Allergy
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Treatment
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Epinephrine
Respiratory support
Prevention: skin testing
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Drug Interactions
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Aminoglycosides
Penicillin V
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Penicillinase-Resistant Penicillins
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Available in the United States
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Nafcillin
Oxacillin
Dicloxacillin
MRSA: methicillin-resistant Staphylococcus
aureus
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Broad-Spectrum Penicillins
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Broad-spectrum penicillins (aminopenicillins)
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Ampicillin (Principen)
Amoxicillin (Amoxil, DisperMox, Moxatag, Trimox)
Adverse effects
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Rash
Diarrhea
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Extended-Spectrum Penicillins
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Extended-spectrum penicillins
(antipseudomonal penicillins)
 Piperacillin
• Broad-spectrum, but penicillinase-sensitive
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Penicillin Combinations
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Beta-lactamase inhibitors
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Clavulanic acid, tazobactam, sulbactam
Extends antimicrobial spectrum when
combined with penicillinase-sensitive
antibiotics
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Ampicillin/sulbactam (Unasyn)
Amoxicillin/clavulanic acid (Augmentin)
Ticarcillin/clavulanic acid (Timentin)
Piperacillin/tazobactam (Zosyn)
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