Cavanagh, Jorunn Pauline2; Granslo, Hildegunn Norbakken3; Fredheim, Elizabeth Aarag3; Christophersen, Lars3; Jensen, Peter Østrup7; Thomsen, Kim8; van Gennip, Maria6; Klingenberg, Claus3; Flaegstad, Trond3; Moser, Claus9; Alhede, Maria9
1 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. firstname.lastname@example.org unknown4 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet5 LUKKET: 2012 Afdeling for Eksperimentel Medicin, Faculty of Health and Medical Sciences, Københavns Universitet6 Department of Systems Biology7 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet8 LUKKET: 2012 Afdeling for Eksperimentel Medicin, Faculty of Health and Medical Sciences, Københavns Universitet9 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Journal of Antimicrobial Chemotherapy, 2013, Vol 68, Issue 9, p. 2106-10