Novel in vivo mouse model of shoulder implant infection

Abstract

Background: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement. Methods: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 μL of 1 × 10 3 (e3), or 1 × 10 4 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 μL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. Results: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. Discussion: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. Conclusion: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.

Fighting Staphylococcus aureus infections with light and photoimmunoconjugates

“…Although the scavenging of ROS is of critical importance for human health, the strong antioxidant activity as presented by HSA is a potential hurdle for aPDT with 1D9-700DX in clinical settings. This applies in particular to aPDT in the context of image-guided debridement of infected implants and tissue, where blood will be present due to the surgical procedure (20,21). Indeed, we show that the presence of human plasma with its high HSA content can seriously interfere with aPDT using 1D9-700DX.…”

“…We have previously developed a fully human mAb -1D9 -which targets the immunodominant staphylococcal antigen A (IsaA), a strictly conserved noncovalently cell wall-bound lytic transglycosylase that is exposed on the surface of all S. aureus isolates tested so far (14)(15)(16)(17)(18). 1D9 was preclinically shown to be highly effective in the noninvasive diagnosis of S. aureus soft tissue infections, as well as spinal and shoulder implant infections in mice using PET-CT or in vivo fluorescence imaging (19)(20)(21). Importantly, this diagnostic approach offers the advantage that it can distinguish infection from aseptic inflammation because it directly targets the causative pathogen.…”

“…Importantly, this diagnostic approach offers the advantage that it can distinguish infection from aseptic inflammation because it directly targets the causative pathogen. Accordingly, the fluorescently labeled 1D9 was shown to facilitate intraoperative image-guided selective debridement of S. aureus biofilms on spinal and shoulder implants (20,21).…”

Active rheumatoid arthritis in a mouse model is not an independent risk factor for periprosthetic joint infection

“…Bacteria was prepared according to recently published protocols [46][47][48][49][50][51]. Briefly, S. aureus Xen36 was first streaked onto tryptic soy broth (TSB) agar kanamycin plates (TSB plus 1.5% Bacto agar; BD Biosciences) and grown for approximately 24 hours at 37˚C.…”

Active Rheumatoid Arthritis in a Mouse Model is not an Independent Risk Factor for Periprosthetic Joint Infection

“…Bacteria was prepared according to recently published protocols [42][43][44][45][46][47] . Briefly, S. aureus Xen36 was first streaked onto tryptic soy broth (TSB) agar kanamycin plates (TSB plus 1.5% Bacto agar; BD Biosciences) and grown for approximately 24 hours at 37°C.…”