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

Jorunn Pauline Cavanagh, Hildegunn Norbakken Granslo, Elizabeth Aarag Fredheim, Lars Christophersen, Peter Østrup Jensen, Kim Thomsen, Maria van Gennip, Claus Klingenberg, Trond Flaegstad, Claus Moser, Maria Alhede

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    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.
    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

    Keywords

    • 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

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