Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo.

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.

Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection.

INTRODUCTION: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model. METHODS: A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus. A dose of 400 µg and 200 µg of antibody-photosensitizer conjugate 4497-IgG-IRDye700DXwas administered intravenously to two groups of 5 mice. In addition, multiple control groups (vancomycin treated, unconjugated IRDye700DX and IRDye700DX conjugated to a non-specific antibody) were used to verify anti-microbial effects. RESULTS: In vitro results of 4497-IgG-IRDye700DX on pre-colonized (biofilm) implants showed significant (p<0.01) colony-forming units (CFU) reduction at a concentration of 5 µg of the antibody-photosensitizer conjugate. In vivo, treatment with 4497-IgG-IRDye700DX showed no significant CFU reduction at the implant infection. However, tissue around the implant did show a significant CFU reduction with 400 µg 4497-IgG-IRDye700DX compared to control groups (p = 0.037). CONCLUSION: This study demonstrated the antimicrobial potential of photoimmunotherapy for selectively eliminating S. aureus in vivo. However, using a solid implant instead of a catheter could result in an increased bactericidal effect of 4497-IgG-IRDye700DX and administration locally around an implant (per operative) could become valuable applications in patients that are difficult to treat with conventional methods. We conclude that photoimmunotherapy could be a potential additional therapy in the treatment of implant related infections, but requires further improvement.

Long-term outcome of two-stage revision surgery after hip and knee prosthetic joint infections: an observational study.

Introduction: Two-stage revision surgery is the most frequently performed procedure in patients with a chronic periprosthetic joint infection (PJI). The infection eradication rates in the current literature differ between 54 % and 100 %, which could be attributed to different treatment strategies. The aim of this study was to retrospectively evaluate the infection eradication rate in patients with chronic PJI treated with two-stage revision surgery of the hip or knee in primary and re-revision cases. Methods: All patients treated with a two-stage revision for chronic PJI between 2005 and 2011 were analysed. Patient and infection characteristics were retrieved. Primary outcome was successful infection eradication at last follow-up. Successful eradication is specified as no need for subsequent revision surgery or suppressive antibiotic treatment. Results: Forty-seven patients were treated with a two-stage revision. Infection eradication was achieved in 36 out of 47 cases. Thirty-eight patients had positive cultures: 35 monomicrobial infections and 3 polymicrobial infections. Nine cases of culture-negative infections were identified. Accompanying eradication rates were 26 out of 35 cases, 2 out of 3 cases, and 8 out of 9 cases respectively. Mean follow-up was 128 (27-186) months. For hip and knee revisions the eradication rates were 22 out of 31 cases and 14 out of 16 cases respectively. After primary arthroplasty the infection was eradicated in 29 out of 38 cases and after re-revision in 7 out of 9 cases. Conclusion: In this study, the infection eradication rate for two-stage revision surgery after PJI of the hip and knee in primary and re-revision cases was 77 %. No statistically significant patient, infection and micro-organism characteristics were found which influence the infection eradication rates at long-term follow-up of 128 (27-186) months.