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The Role of Negative-Pressure Wound Therapy in Patients with Fracture-Related Infection:A Systematic Review and Critical Appraisal

INTRODUCTION: Fracture-related infection (FRI) is a severe musculoskeletal complication in orthopedic trauma surgery, causing challenges in bony and soft tissue management. Currently, negative-pressure wound therapy (NPWT) is often used as temporary coverage for traumatic and surgical wounds, also in cases of FRI. However, controversy exists about the impact of NPWT on the outcome in FRI, specifically on infection recurrence. Therefore, this systematic review qualitatively assesses the literature on the role of NPWT in the management of FRI. METHODS: A literature search of the PubMed, Embase, and Web of Science database was performed. Studies that reported on infection recurrence related to FRI management combined with NPWT were eligible for inclusion. Quality assessment was done using the PRISMA statement and the Newcastle-Ottawa Quality Assessment Scale. RESULTS: After screening and quality assessment of 775 unique identified records, eight articles could be included for qualitative synthesis. All eight studies reported on infection recurrence, which ranged from 2.8% to 34.9%. Six studies described wound healing time, varying from two to seven weeks. Four studies took repeated microbial swabs during subsequent vacuum dressing changes. One study reported newly detected pathogens in 23% of the included patients, and three studies did not find new pathogens. CONCLUSION: This review provides an assessment of current literature on the role of NPWT in the management of soft tissue defects in patients with FRI. Due to the lack of uniformity in included studies, conclusions should be drawn with caution. Currently, there is no clear scientific evidence to support the use of NPWT as definitive treatment in FRI. At this stage, we can only recommend early soft tissue coverage (within days) with a local or free flap. NPWT may be safe for a few days as temporarily soft tissue coverage until definitive soft tissue management could be performed. However, comparative studies between NPWT and early wound closure in FRI patients are needed

Deformable titanium for acetabular revision surgery: a proof of concept

Custom-made triflange acetabular implants are increasingly used in complex revision surgery where supporting bone stock is diminished. In most cases these triflange cups induce stress-shielding. A new concept for the triflange is introduced that uses deformable porous titanium to redirect forces from the acetabular rim to the bone stock behind the implant and thereby reduces further stress-shielding. This concept is tested for deformability and primary stability.Three different designs of highly porous titanium cylinders were tested under compression to determine their mechanical properties. The most promising design was used to design five acetabular implants either by incorporating a deformable layer at the back of the implant or by adding a separate generic deformable mesh behind the implant. All implants were inserted into sawbones with acetabular defects followed by a cyclic compression test of 1800N for 1000 cycles.The design with a cell size of 4 mm and 0.2 mm strut thickness performed the best and was applied for the design of the acetabular implants. An immediate primary fixation was realized in all three implants with an incorporated deformable layer. One of the two implants with a separate deformable mesh needed fixation with screws. Cyclic tests revealed an average additional implant subsidence of 0.25 mm that occurred in the first 1000 cycles with minimal further subsidence thereafter.It is possible to realize primary implant fixation and stability in simulated large acetabular revision surgery using a deformable titanium layer behind the cup. Additional research is needed for further implementation of such implants in the clinic

The EBJIS definition of periprosthetic joint infection A PRACTICAL GUIDE FOR CLINICIANS

AIMS: The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. METHODS: This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. RESULTS: This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. CONCLUSION: The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18-25

Antibacterial and anti-inflammatory properties of host defense peptides against Staphylococcus aureus

Cationic host defense peptides (HDPs) are a promising alternative to antibiotics in the fight against Staphylococcus aureus infections. In this study, we investigated the antibacterial and immunomodulatory properties of three HDPs namely IDR-1018, CATH-2, and LL-37. Although all three HDPs significantly inhibited LPS-induced activation of human macrophages, only CATH-2 prevented S. aureus growth. When applied to different infection models focused on intracellularly surviving bacteria, only IDR-1018 showed a consistent reduction in macrophage bacterial uptake. However, this observation did not correlate with an increase in killing the efficiency of intracellular S. aureus. Here, we conclude that despite the promising antibacterial and anti-inflammatory properties of the selected HDPs, macrophages' intrinsic antibacterial functions were not improved. Future studies should either focus on combining different HDPs or using them synergistically with other antibacterial agents to improve immune cells' efficacy against S. aureus pathogenesis

Sonication Leads to Clinically Relevant Changes in Treatment of Periprosthetic Hip or Knee Joint Infection

Background: Diagnosis of periprosthetic joint infection (PJI) can be troublesome. Sonication can be a helpful tool in culturing bacteria that are difficult to detect with standard tissue cultures. Aim of this study is to evaluate the clinical importance of our standardized sonication protocol in detecting periprosthetic joint infection. Materials and methods: All patients with revision surgery of a hip or knee prosthesis between 2011 and 2016 were retrospectively reviewed and divided in two groups: clinically suspected of infection or not suspected of infection. For both tissue culture and implant sonication, calculations of sensitivity and specificity were performed. Clinical relevance of sonication was evaluated by calculating in which percentage of patients' sonication influenced clinical treatment. Results: 226 patients with revision of a total hip prosthesis (122 patients) or a total knee prosthesis (104 patients) were included. Sensitivity of perioperatively taken tissue cultures was 94.3% and specificity was 99.3%. For sonication sensitivity was 80.5% and specificity was 97.8%. In the infection group eight patients (9%) with only one positive tissue culture and a positive sonication fluid culture with the same pathogen were found. Interpretation: Although sensitivity and specificity of sonication was lower compared to tissue cultures, periprosthetic joint infection could only be established in 8 patients (9%) suspected of infection because of a positive result of the sonication fluid culture. Sonication leads to clinically relevant changes in treatment and seems therefore to be a helpful diagnostic tool in clinical practice

Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo

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

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