<span class="paragraphSection"><div class="boxTitle">Abstract</div>Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against <span style="font-style:italic;">S. aureus</span> biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant <span style="font-style:italic;">S. aureus</span> and methicillin-susceptible <span style="font-style:italic;">S. aureus</span> isolates from patients with device-related infections grown under in vivo–relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c<sup>2,5Leu</sup> variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating <span style="font-style:italic;">S. aureus</span> biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c<sup>2,5Leu</sup>, alone or in combination with other AMPs, in the treatment of <span style="font-style:italic;">S. aureus</span> intravenous catheter infections.</span>
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