Surgical Debridement Is Superior to Sole Antibiotic Therapy in a Novel Murine Posttraumatic Osteomyelitis Model

Abstract

IntroductionBone infections after trauma, i.e. posttraumatic osteomyelitis, pose one of the biggest problems of orthopedic surgery. Even after sufficient clinical therapy including vast debridement of infected bone and antibiotic treatment, regeneration of postinfectious bone seems to be restricted. One explanation includes the large sized defects resulting from sufficient debridement. Furthermore, it remains unclear if inflammatory processes after bone infection do affect bone regeneration. For continuing studies in this field, an animal model is needed where bone regeneration after sufficient treatment can be studied in detail.MethodsFor this purpose we created a stable infection in murine tibiae by Staphylococcus aureus inoculation. Thereafter, osteomyelitic bones were debrided thoroughly and animals were subsequently treated with antibiotics. Controls included debrided, non-infected, as well as infected animals exclusively treated with antibiotics. To verify sufficient treatment of infected bone, different assessments detecting S. aureus were utilized: agar plates, histology and RT-qPCR.ResultsAll three detection methods revealed massive reduction or eradication of S. aureus within debrided bones 1 and 2 weeks postoperatively, whereas sole antibiotic therapy could not provide sufficient treatment of osteomyelitic bones. Debrided, previously infected bones showed significantly decreased bone formation, compared to debrided, non-infected controls.DiscussionThus, the animal model presented herein provides a reliable and fascinating tool to study posttraumatic osteomyelitis for clinical therapies.

Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity

“…Diminished bone healing after osteomyelitic infections is a common clinical issue of orthopedic surgery . Even after sufficient debridement, bone regeneration seemed to be decreased, although the direct cause has been completely removed . Thus the aim of this study was to reveal further details of the diminished bone regeneration after posttraumatic osteomyelitis.…”

“…About 126 C57BL/6J male and female mice, 12 weeks old with an average weight of 25 g, were used for this project. Surgical steps were performed, as previously described . Briefly, after placement of a skin incision over the proximal medial tibia, a hole (1 mm in diameter) was drilled into the proximal medial tibia.…”

“…Our previous study revealed that bone regeneration in posttraumatic osteomyelitis seemed to be still impaired, even after eradication of the basic cause that is, S. aureus . These findings evolved from a new mouse model of posttraumatic osteomyelitis . In this study tibiae of C57BL/6J mice were infected by inoculation of S. aureus .…”

“…After radical debridement and bacterial eradication, these mice showed significantly diminished formation of new bone in comparison to control group. Moreover, the status of surgical debridement in treatment of bone infections was investigated . Profound knowledge of osteomyelitic markers and causes for diminished bone regeneration after infection is missing.…”

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…10,21,22 Its superiority to antibiotic therapy alone has been emphasized in numerous studies. [22][23][24] This procedure is followed by postoperative, long-term administration of antibiotics. Bacteria can develop resistance to these drugs over time due to: (a) SCV formation, (b) biofilm formation, and/or (c) acquired genetic changes.…”