Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model
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Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model. / Cavanagh, Jorunn Pauline; Granslo, Hildegunn Norbakken; Fredheim, Elizabeth Aarag; Christophersen, Lars; Jensen, Peter Østrup; Thomsen, Kim; van Gennip, Maria; Klingenberg, Claus; Flaegstad, Trond; Moser, Claus; Alhede, Maria.
In: The Journal of antimicrobial chemotherapy, Vol. 68, No. 9, 09.2013, p. 2106-10.Research output: Contribution to journal › Journal article › Research › peer-review
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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. 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.
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. 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.
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
VL - 68
SP - 2106
EP - 2110
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 9
ER -
ID: 105877305