INTRODUCTION: Up to 50% of type 3b compound fractures are complicated by biofilm infections [1]. Lactoferrin (Lf), a glycoprotein with antibiofilm properties, is found naturally in animal milk [2]. The goal of this study was to: 1) Demonstrate the in vitro anti-biofilm properties of bLf. 2) Translate the antibiofilm activity of bLf to an in vivo periprosthetic, biofilm infected tibia rodent model. METHODS: 1) S. aureus Xen-36 biofilm generated in a bioreactor on metal coupons was tested against cefazolin (CEF) and flucloxacillin (FLU) with or without bLf. S. aureus colonies (CFU) were enumerated. 2) Surgery was performed on rats (n = 40), where the tibia was drilled and inoculated with Ten µL (≈107 CFU) of S. aureus biofilm. A steel pin was placed within the tibia, and the wound treated with STIMULAN® beads loaded with 4 treatment groups: 1) Control (empty), 2) bLf 3) FLU, 4) bLf and FLU. At day 7 rats were euthanized for tissue/pin collection and enumeration. RESULTS: In vitro: bLf augments the anti-biofilm activity of CEF and FLU 102 to 105 times greater than the antibiotic alone (p<0.001), and in combination with FLU in beads, significantly eradicates S. aureus biofilm infection in vivo compared against controls (6/10 eliminated infection, p<0.001). DISCUSSION: bLf holds promise as an anti-infective in battlefield relevant open fractures, supported by the anti-biofilm properties of bLF highlighted within this research. REFERENCES: 1) Gustilo R, et al., J Trauma. 24:742-746, 1984. 2) Gould G, et al., J Food Prot 59:82-86, 1996.