Effect Of Vancomycin And Teicoplanin Alone Or In

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Effect Of Vancomycin And Teicoplanin Alone Or In

  1. 1. Effect of Vancomycin and Teicoplanin Alone or in combination with Fusidic Acid or Amikacin against Methicillin-Resistant Staphylococci Roussel-Delvallez et al. Journal of Chemotherapy 1997 Dr Preneshni R Naicker
  2. 2. Vancomycin <ul><li>Glycopeptide </li></ul><ul><li>Binds to the precursors of cell wall synthesis </li></ul><ul><li>Primary target D-ala-D-ala subunits </li></ul><ul><li>This interferes with the ability of the PBP enzymes, such as transpeptidases and transglycosylases, to incorporate the precursors into the growing cell wall. </li></ul>
  3. 3. Teicoplanin <ul><li>Glycopeptide </li></ul><ul><li>Complex of 5 closely related glycopeptides </li></ul><ul><li>Similar structure to Vancomycin </li></ul><ul><li>Binds to D-ala-D-ala subunits </li></ul>
  4. 4. Fusidic Acid <ul><li>Derived from Fusidium coccineum </li></ul><ul><li>Binds to Elongation Factor G (EF-G) </li></ul><ul><li>EF-G is a bacterial protein that is necessary for translocation on the bacterial ribosome during protein synthesis. </li></ul><ul><li>Further protein synthesis is inhibited. </li></ul>
  5. 5. Amikacin <ul><li>Aminoglycoside </li></ul><ul><li>Inhibit bacterial protein synthesis </li></ul><ul><li>Binds to protein receptors on 30S ribosomal subunit </li></ul>
  6. 6. <ul><li>Synergy : the activity of the antimicrobial combination is substantially greater than the activity of the single most active drug alone </li></ul><ul><li>Indifference : the activity of the combination is no better or worse than the single most active drug alone </li></ul><ul><li>Antagonism : the activity of the combination is substantially less than the activity of the single most active drug alone. </li></ul>
  7. 7. Synergy testing methods <ul><li>Checkerboard Assay </li></ul><ul><li>Time-Kill Assay </li></ul>
  8. 8. Introduction <ul><li>MRSA and CNS are a major cause of nosocomial infection </li></ul><ul><li>Vancomycin remains the drug of choice for treating Methicillin-Resistant Staphylococci </li></ul><ul><li>A possibly less nephrotoxic and ototoxic alternative is Teicoplanin </li></ul><ul><li>Given the slow rate of killing of glycopeptides against staphylococci, attempts have been made to combine these with other antibiotics </li></ul>
  9. 9. Aim <ul><li>To study the action of two glycopeptides (Vancomycin and Teicoplanin) alone or in combination with amikacin or fusidic acid, against 10 non-repetitive strains of methicillin-resistant staphylococci </li></ul>
  10. 10. Materials and Methods <ul><li>Strains </li></ul><ul><li>Staph aureus 5 </li></ul><ul><li>Staph epi 3 </li></ul><ul><li>Staph haem 2 </li></ul><ul><li>Sites </li></ul><ul><li>B/C 7 </li></ul><ul><li>Brush 2 </li></ul><ul><li>CSF 1 </li></ul>
  11. 11. <ul><li>Antimicrobials </li></ul><ul><li>V - vancomycin </li></ul><ul><li>T - teicoplanin </li></ul><ul><li>AKN - amikacin </li></ul><ul><li>FA - fusidic acid </li></ul>
  12. 12. <ul><li>MIC </li></ul><ul><li>Broth dilution </li></ul><ul><li>MIC – the lowest concentration that completely inhibited growth </li></ul><ul><li>Killing curve method </li></ul><ul><li>Synergism : >100 fold increase in killing at 24h with the combination in comparison with the most active single drug </li></ul>
  13. 13. <ul><li>Antagonism : <100-fold decrease in killing at 24h with the combination in comparison with the most active single drug. </li></ul>
  14. 14. Results 16 0.125 1 1 10 S epi 16 0.25 2 1 9 S epi 16 0.5 2 2 8 S haem 16 0.25 1 1 7 S haem 8 0.25 2 1 6 S epi 32 0.25 1 1 5 S aur 16 0.125 2 2 4 S aur 16 0.125 4 1 3 S aur 16 0.25 2 1 2 S aur 32 0.25 4 1 1 S aur AKN(16-64) FA(2-16) T(8-32) V(4-32) Strains
  15. 15. I:6 S:4 T + AKN A:2 I:5 S:3 V + AKN A:6 I:2 S:2 T + FA A: 10 V + FA T0 + 24h Combinations/Time
  16. 16. Discussion <ul><li>Glycopeptides exhibit slower killing rates in vitro </li></ul><ul><li>Teicoplanin has the same slow bactericidal activity in 48h </li></ul><ul><li>Combinations of FA + V and FA + T show an antagonistic affect </li></ul><ul><li>AKN does not inhibit the action of V or T </li></ul><ul><li>but does increase the spectrum of activity. </li></ul>
  17. 17. <ul><li>Thank you </li></ul>

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