title: Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model.
abstract: OBJECTIVE
  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.
authors: Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. pauline.cavanagh@uit.no
authors: Jorunn Pauline
authors: JP
authors: Cavanagh
authors: Hildegunn Norbakken
authors: HN
authors: Granslo
authors: Elizabeth Aarag
authors: EA
authors: Fredheim
authors: Lars
authors: L
authors: Christophersen
authors: Peter Østrup
authors: PØ
authors: Jensen
authors: Kim
authors: K
authors: Thomsen
authors: Maria
authors: M
authors: Van Gennip
authors: Claus
authors: C
authors: Klingenberg
authors: Trond
authors: T
authors: Flaegstad
authors: Claus
authors: C
authors: Moser
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D055499:Catheter-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D057786:Peptidomimetics / Q000008:administration & dosage*; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D057786:Peptidomimetics; D014640:Vancomycin
keywords: biofilms; device-related peritonitis; mouse model