POLYPEPTIDE ANTIBACTERIALS
Outline

Overview

• Group based only on structural elements -- amino acids
• Members
  • Vancomycin
    • Systemic and GI infections
  • Polymyxin B
    • Serious systemic toxicity -- renal
    • Gram(-) spectrum
    • Now mainly topical
  • Bacitracin
    • Serious systemic toxicity -- renal
    • Gram(+) spectrum
    • Cell wall synthesis inhibitor
    • Now topical only
    • Some derivatives feed additives for food producing animals

  Vancomycin

  Structure and Chemistry

  • Glycopeptide -- MW 1500

  Mechanism of Action / Spectrum

  • Inhibits cell wall synthesis
    • Inhibits peptidoglycan synthase
    • Prevents formation of polymer chains
  • Cidal
  • Still active against methicillin-resistant Staph
  • Also an effect on RNA synthesis
  • Narrow spectrum -- gram(+)
  • Drug of choice -- Antibiotic-Associated Pseudomemranous Enterocolitis

  Pharmacokinetics

  • PO -- Not absorbed, so safe!
  • IV (preferrably infusion) for systemic action
    • SLOW avoid cardiac arrest and
    • histamine release -- red-neck syndrome & hypotension
  • Widely distributed
  • Renal elimination -- glomerular filtration

  Adverse Effects

  • Oral -- few adverse effects
  • IM/SC or perivascular
    • Highly irritating
    • Sterile abscessation
    • Pain
  • IV -- many
    • if too rapid -- histamine release
      • red-neck syndrome
      • hypotension
    • renal toxicity -- not as bad with purer modern preparations
    • Many others -- see reference

  Study Questions

  1. What is the general spectrum of activity of vancomycin? How do its therapeutic uses orally compare with those for which it is used parenterally?
  2. How does the toxicity of vancomycin given orally compare with that when it is used parenterally?
  3. How does the mechanism of action of vancomycin compare to that of the beta-lactams? Is it similarly dependent on growing organisms for its maximal effect?
  4. Why are bacitracin and polymyxin B used primarily topically today?
  5. How do the antibacterial spectra of bacitracin and polymyxin B compare? Why might they be frequently combined in topical over-the-counter (OTC) preparations?
  
  

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  Gordon L. Coppoc, DVM, PhD
  Professor of Veterinary Pharmacology
  Head, Department of Basic Medical Sciences
  School of Veterinary Medicine
  Purdue University
  West Lafayette, IN 47907-1246
  Tel: 317-494-8633Fax: 317-494-0781
  Email: coppoc@vet.purdue.edu
  
  Last modified 10:13 PM on 4/16/96 GLC