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

Research output: Contribution to journalJournal articlepeer-review

  • Jorunn Pauline Cavanagh
  • Hildegunn Norbakken Granslo
  • Elizabeth Aarag Fredheim
  • Lars Christophersen
  • Jensen, Peter Østrup
  • Kim Thomsen
  • Maria van Gennip
  • Claus Klingenberg
  • Trond Flaegstad
  • Moser, Claus Ernst
  • Maria Alhede
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.
Original languageEnglish
JournalThe Journal of antimicrobial chemotherapy
Volume68
Issue number9
Pages (from-to)2106-10
Number of pages5
ISSN0305-7453
DOIs
Publication statusPublished - Sep 2013

    Research areas

  • Animals, Anti-Bacterial Agents, Bacterial Load, Catheter-Related Infections, Disease Models, Animal, Female, Mice, Mice, Inbred BALB C, Peptidomimetics, Peritoneal Dialysis, Peritonitis, Staphylococcal Infections, Staphylococcus epidermidis, Treatment Outcome, Vancomycin

ID: 105877305