Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model

J Antimicrob Chemother. 2013 Sep;68(9):2106-10. doi: 10.1093/jac/dkt161. Epub 2013 May 3.

Abstract

Objectives: Biofilm-forming Staphylococcus epidermidis is a prevalent cause of peritonitis during peritoneal dialysis. We compared the efficacy of a synthetic antimicrobial peptidomimetic (Ltx21) versus vancomycin in a murine model mimicking a device-related peritonitis.

Methods: Silicone implants, pre-colonized with an S. epidermidis biofilm, were inserted into the peritoneal cavity of BALB/c mice. Three groups (36 mice in each) with pre-colonized implants received intraperitoneal treatment with Ltx21, vancomycin or placebo. Mice were euthanized on day 3 (n = 12), day 6 (n = 12) or day 8 (n = 12) post-implantation. Controls were mice with sterile implants (n = 18) and mice without surgery (n = 6). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PF were measured.

Results: Vancomycin resulted in a stronger reduction in cfu counts, both on pre-colonized implants and in PF, compared with Ltx21 and placebo. Complete bacterial clearance of the implants was not achieved in any of the groups. The implants pre-colonized with S. epidermidis 1457 resulted in a low-grade peritonitis. We observed, only on day 6, a significant increase in the PF leucocyte count in the group with pre-colonized implants compared with the group with sterile implants (P = 0.0364).

Conclusions: Treatment with vancomycin or Ltx21 was not sufficient to achieve complete bacterial clearance of implants, underlining the difficulties of treating such infections. The low-grade infection may attenuate the inflammatory response and contribute to impaired bacterial clearance.

Keywords: biofilms; device-related peritonitis; mouse model.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Bacterial Load
  • Catheter-Related Infections / drug therapy*
  • Catheter-Related Infections / microbiology
  • Disease Models, Animal
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Peptidomimetics / administration & dosage*
  • Peritoneal Dialysis / adverse effects
  • Peritonitis / drug therapy*
  • Peritonitis / microbiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus epidermidis / drug effects*
  • Treatment Outcome
  • Vancomycin / administration & dosage*

Substances

  • Anti-Bacterial Agents
  • Peptidomimetics
  • Vancomycin