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

TY - JOUR

T1 - Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model

AU - Cavanagh, Jorunn Pauline

AU - Granslo, Hildegunn Norbakken

AU - Fredheim, Elizabeth Aarag

AU - Christophersen, Lars

AU - Jensen, Peter Østrup

AU - Thomsen, Kim

AU - van Gennip, Maria

AU - Klingenberg, Claus

AU - Flaegstad, Trond

AU - Moser, Claus

AU - Alhede, Maria

PY - 2013/9

Y1 - 2013/9

N2 - 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. Micewereeuthanizedonday3(n1/412),day6(n1/412) orday8(n1/412) post-implantation. Controlswere mice with sterile implants (n1/418) and mice without surgery (n1/46). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PFwere 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 implantswas not achieved in anyof the groups. The implants pre-colonized with S. epidermidis 1457 resulted in a low-grade peritonitis. We observed, onlyon day 6, a significant increase in the PF leucocyte count in the group with pre-colonized implants compared with the group with sterile implants (P1/40.0364). 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 infectionmayattenuate the inflammatory response and contribute to impaired bacterial clearance

AB - 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. Micewereeuthanizedonday3(n1/412),day6(n1/412) orday8(n1/412) post-implantation. Controlswere mice with sterile implants (n1/418) and mice without surgery (n1/46). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PFwere 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 implantswas not achieved in anyof the groups. The implants pre-colonized with S. epidermidis 1457 resulted in a low-grade peritonitis. We observed, onlyon day 6, a significant increase in the PF leucocyte count in the group with pre-colonized implants compared with the group with sterile implants (P1/40.0364). 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 infectionmayattenuate the inflammatory response and contribute to impaired bacterial clearance

KW - Animals

KW - Anti-Bacterial Agents

KW - Bacterial Load

KW - Catheter-Related Infections

KW - Disease Models, Animal

KW - Female

KW - Mice

KW - Mice, Inbred BALB C

KW - Peptidomimetics

KW - Peritoneal Dialysis

KW - Peritonitis

KW - Staphylococcal Infections

KW - Staphylococcus epidermidis

KW - Treatment Outcome

KW - Vancomycin

U2 - 10.1093/jac/dkt161

DO - 10.1093/jac/dkt161

M3 - Journal article

C2 - 23645587

SN - 0305-7453

VL - 68

SP - 2106

EP - 2110

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 9

ER -