Orthopedic Implant-associated Infections Research Articles

Drug delivery nanoplatform for orthopaedic-associated infections

The number of patients in need of orthopaedic implants has increased rapidly over the past few years. Implant associated infections that are created after an invasive orthopaedic surgery are one of the major causes of implant failure. In this work, a drug delivery nano platform system was fabricated, consisted of Polycaprolactone (PCL) scaffolds loaded with the antibiotic drug vancomycin via Electrospinning process. Titanium implants’ surface has been modified with non-woven fibrous coatings while the efficacy and toxicity on fibroblasts were investigated in vitro. Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) measurements showed the successful fabrication of those structures. Cytotoxicity studies took place in order to examine the cytocompatibilty of the nanoplatform. MTT assay and methylene blue staining showed an excellent cell adhesion and proliferation, thus enhance the cytocompatible behavior in vitro. Drug release kinetics further took place in line with degradation studies in order to evaluate the mass loss of polymers. This drug delivery nano platform is a promising nanovehicle to prevent and treat orthopedic implant-associated infections along with a simultaneously release of the drug in a controllable and sustainable manner.

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes.

Infection is one of the major causes of failure of orthopedic implants. Our previous study demonstrated that nanotube modification of the implant surface, together with nanotubes loaded with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), could effectively inhibit bacterial adherence and biofilm formation in vitro. Therefore, the aim of this study was to further investigate the in vitro cytocompatibility with osteogenic cells and the in vivo anti-infection activity of titanium implants with HACC-loaded nanotubes (NT-H). The titanium implant (Ti), nanotubes without polymer loading (NT), and nanotubes loaded with chitosan (NT-C) were fabricated and served as controls. Firstly, we evaluated the cytocompatibility of these specimens with human bone marrow-derived mesenchymal stem cells in vitro. The observation of cell attachment, proliferation, spreading, and viability in vitro showed that NT-H has improved osteogenic activity compared with Ti and NT-C. A prophylaxis rat model with implantation in the femoral medullary cavity and inoculation with methicillin-resistant Staphylococcus aureus was established and evaluated by radiographical, microbiological, and histopathological assessments. Our in vivo study demonstrated that NT-H coatings exhibited significant anti-infection capability compared with the Ti and NT-C groups. In conclusion, HACC-loaded nanotubes fabricated on a titanium substrate show good compatibility with osteogenic cells and enhanced anti-infection ability in vivo, providing a good foundation for clinical application to combat orthopedic implant-associated infections.

Electrophoretic Deposition of Chitosan Coatings Modified with Gelatin Nanospheres To Tune the Release of Antibiotics.

Orthopedic and dental implants are increasingly used in the medical field in view of their high success rates. Implant-associated infections, however, still occur and are difficult to treat. To combat these infections, the application of an active coating to the implant surface is advocated as an effective strategy to facilitate sustained release of antibacterial drugs from implant surfaces. Control over this release is, however, still a major challenge. To overcome this problem, we deposited composite coatings composed of a chitosan matrix containing gelatin nanospheres loaded with antibiotics onto stainless steel plates by means of the electrophoretic deposition technique. The gelatin nanospheres were distributed homogeneously throughout the coatings. The surface roughness and wettability of the coatings could be tuned by a simple adjustment of the weight ratio between the gelatin nanospheres and chitosan. Vancomycin and moxifloxacin were released in sustained and burst-type manners, respectively, while the coatings were highly cytocompatible. The antibacterial efficacy of the coatings containing different amounts of antibiotics was tested using a zone of inhibition test against Staphylococcus aureus, which showed that the coatings containing moxifloxacin exhibited an obvious inhibition zone. The coatings containing a high amount of vancomycin were able to kill bacteria in direct contact with the implant surface. These results suggest that the antibacterial capacity of metallic implants can be tuned by orthogonal control over the release of (multiple) antibiotics from electrophoretically deposited composite coatings, which offers a new strategy to prevent orthopedic implant-associated infections.

Preventing Orthopaedic Implant-Associated Infections: the Sheep as an Animal Model

Preventing Orthopaedic Implant-Associated Infections: the Sheep as an Animal Model

Concentration of Sonication Fluid through Centrifugation Is Superior to Membrane Filtration for Microbial Diagnosis of Orthopedic Implant-Associated Infection.

Microbial identification of orthopedic implant-associated infections using sonication fluid (SF) submitted to a concentration step by membrane filtration (SMF) was compared with the standard centrifugation (SC) method. Among 33 retrieved infected implants, sonication identified microorganisms in 26 (78.8%). The sensitivity of SC was higher than that of SMF (78.8% versus 30.3%; P < 0.001).

Cathodic Electrical Stimulation Combined With Vancomycin Enhances Treatment of Methicillin-resistant Staphylococcus aureus Implant-associated Infections.

Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at -1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10(3); SD, 6.3 × 10(3)) group were less than those from the CONT (mean, 1.3 × 10(6); SD, 2.8 × 10(6); 95% confidence interval [CI] of difference, -4.3 × 10(5) to -9.9 × 10(3); p < 0.001), STIM (mean, 1.4 × 10(6); SD, 2.0 × 10(6); 95% CI of difference, -2.1 × 10(6) to -1.8 × 10(3); p = 0.002), and VANCO (mean, 5.8 x 10(4); SD, 5.7 × 10(4); 95% CI of difference, -6.4 × 10(4) to -1.7 × 10(4); p < 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10(1); SD, 1.1 × 10(2)) were less than those from the CONT (mean, 2.8 × 10(5); SD, 4.8 × 10(5); 95% CI of difference, -9.4 × 10(4) to -5.0 × 10(3); p < 0.001) and STIM (mean, 2.6 × 10(4); SD, 2.5 × 10(4); 95% CI of difference, -4.1 × 10(4) to -1.6 × 10(3); p < 0.001) groups. The VANCO group (4.3 × 10(5); SD, 6.3 × 10(2)) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, -9.3 × 10(4) to -4.5 × 10(3); p < 0.001) and STIM (95% CI of difference, -4.0 × 10(4) to -1.5 × 10(3); p < 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10(4); SD, 6.0 × 10(4)), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10(1); SD, 1.2 × 10(2); 95% CI of difference, -4.9 × 10(3) to -3.0 × 10(2); p < 0.001) and the VANCO group (mean, 6.8 × 10(1); SD, 9.2 × 10(1); 95% CI of difference, -4.9 × 10(3) to -2.8 × 10(2); p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.

Antibiotic susceptibility of Propionibacterium acnes isolated from orthopaedic implant-associated infections

IntroductionProsthetic joint infections (PJIs) caused by Propionibacterium acnes account for a larger proportion of the total number of PJIs than previously assumed and thus knowledge of the antimicrobial susceptibility patterns of P. acnes is of great value in everyday clinical practice. Materials and methodsUsing Etest, the present study investigated the susceptibility of 55 clinical isolates of P. acnes, obtained from orthopaedic implant-associated infections of the knee joint (n = 5), hip joint (n = 17), and shoulder joint (n = 33), to eight antimicrobial agents: benzylpenicillin, clindamycin, metronidazole, fusidic acid, doxycycline, moxifloxacin, linezolid and rifampicin. Synergy testing was also conducted, in which rifampicin was combined with each of the remaining seven antibiotics. ResultsAll isolates (n = 55) were susceptible to most of the antibiotics tested, with the exception of 100% resistance to metronidazole, five (9.1%) isolates displaying decreased susceptibility to clindamycin, and one (1.8%) to moxifloxacin. None of the antimicrobial agents investigated were synergistic with each other when combined and nine isolates were antagonistic for various antimicrobial combinations. The majority of the antimicrobial combinations had an indifferent effect on the isolates of P. acnes. However, the combination of rifampicin and benzylpenicillin showed an additive effect on nearly half of the isolates. ConclusionAlmost all P. acnes, isolated from orthopaedic implant-associated infections, predominantly PJIs, were susceptible to the antibiotics tested, with the exception of complete resistance to metronidazole. Synergy test could not demonstrate any synergistic effect but additive effects were found when combining various antibiotics. Antagonistic effects were rare.

Improved Diagnosis of Infection Associated with Osteosynthesis by Use of Sonication of Fracture Fixation Implants

Previous studies have shown that sonication fluid cultures from removed orthopedic devices improved the microbiological diagnosis of orthopedic implant-associated infections; however, few of these investigations have applied sonication to the removed fracture fixation devices to evaluate its utility for the diagnosis of osteosynthesis-associated infection (OAI). We compared sonication fluid to conventional tissue cultures from 180 subjects with different sizes of plates and screws (n = 156), spinal implants (n = 26), and intramedullary nails (n = 3), of whom 125 and 55 subjects had OAI and noninfected osteosynthesis (NIO), respectively. The sensitivity for detecting OAI was 90.4% for sonication fluid culture and 56.8% for periprosthetic tissue cultures (P < 0.05), and the specificities were 90.9% and 96.4%, respectively. Sonication fluid culture detected more pathogens than peri-implant tissue culture (113 versus 71; P < 0.001), while polymicrobial infections were diagnosed by sonication fluid cultures and tissue cultures in 20.8% and 8% (P < 0.001), respectively. Microbiological diagnosis was achieved exclusively by sonication fluid cultures for 47 (90.4%) subjects, and among them, 18 (38.3%) had previously received antibiotics, whereas in five (9.6%) infected subjects, tissue culture was positive and the sonication fluid culture was negative. Among 39 (31.2%) OAI cases receiving antibiotics, the identification of the organisms occurred in 38.5% and 82.1% of the tissue and sonication fluid cultures, respectively (P < 0.049). We demonstrated that sonication fluid culture from removed osteosyntheses has the potential for improving the microbiological diagnosis of OAI.

Characterization and antibacterial performance of electrodeposited chitosan–vancomycin composite coatings for prevention of implant-associated infections

Orthopaedic implant-associated infections are one of the most serious complications in orthopaedic surgery and a major cause of implant failure. In the present work, drug-eluting coatings based on chitosan containing various amounts of vancomycin were prepared by a cathodic electrophoretic deposition process on titanium foils. A three-step release mechanism of the antibiotic from the films in a phosphate-buffered saline solution was noticed. At the early stage, physical encapsulation of the drug in the hydrogel network controlled the release rate. At the late stage, however, in vitro degradation/deattachment of chitosan was responsible for the controlled release. Cytotoxicity evaluation of the drug-eluting coatings via culturing in human osteosarcoma cells (MG-63 osteoblast-like cell line) showed no adverse effect on the biocompatibility. Antibacterial tests against Gram-positive Staphylococcus aureus also demonstrated that the infection risk of titanium foils was significantly reduced due to the antibiotic release. Additionally, in vitro electrochemical corrosion studies by polarization technique revealed that the corrosion current density was significantly lower for the titanium foils with drug-eluting coatings compared to that of uncoated titanium.

Functional Imaging in Diagnostic of Orthopedic Implant-Associated Infections.

Surgeries’ sterile conditions and perioperative antibiotic therapies decrease implant associated infections rates significantly. However, up to 10% of orthopedic devices still fail due to infections. An implant infection generates a high socio-economic burden. An early diagnosis of an infection would significantly improve patients’ outcomes. There are numerous clinical tests to diagnose infections. The “Gold Standard” is a microbiological culture, which requires an invasive sampling and lasts up to several weeks. None of the existing tests in clinics alone is sufficient for a conclusive diagnosis of an infection. Meanwhile, there are functional imaging modalities, which hold the promise of a non-invasive, quick, and specific infection diagnostic. This review focuses on orthopedic implant-associated infections, their pathogenicity, diagnosis and functional imaging.

Extracorporeal shock wave therapy could be a potential adjuvant treatment for orthopaedic implant-associated infections

• Bacterial biofilm can resist antibiotics and the local immune response. • Shock waves can promote osteogenesis and induce neo-vascularization. • Shock waves have a marked bactericidal effect and can remove biofilm. • Shock waves could improve access of drugs and the local immune response to the focus. • Infected target areas should no longer be considered as a contraindication for shock waves. Over the past half-century, biomaterials have been used in orthopaedic surgery world widely, but orthopaedic implant-associated infections (OIAIs) are still a puzzle for orthopaedic surgeons, which may result in prolonged hospitalisation, poor functional status and high costs. The presence of implants increases the risk of microbial infection; moreover, the formation of bacterial biofilm leads to a higher resistance to antibiotics and local immune response. In such cases, conventional systemic delivery of drugs seems to be fairly inefficient and out-dated. Owing to this, debridement and/or removing the implant always become the only solution. Hence, it needs a simple, minimally invasive and effective therapy to eradicate the problem. There are abundant evidences showing that extracorporeal shock wave therapy (ESWT) has favourable effects on stimulating callus formation, inducing angiogenesis, promoting osteogenesis and relieving pain. Studies also indicated that ESWs have a significant bactericidal effect on bacterial strains of bone- and implant-associated infections. Therefore, a hypothesis proposed herein is that ESWT may well be an effective adjuvant treatment for OIAI by controlling infection, inducing bone regeneration and promoting re-osseointegration.

Presence of fibrinogen-binding adhesin gene in Staphylococcus epidermidis isolates from central venous catheters-associated and orthopaedic implant-associated infections

Attention has recently been paid to identify and elucidate those pathogenetic mechanisms, which play a significant role in sustaining the early phases of Staphylococcus epidermidis colonisation and infection development. Several analogies with the physiology of Staphylococcus aureus, a more thoroughly investigated pathogen, have lead to carefully consider all bacterial surface components that mediate cell adhesion. This study aimed at investigating the presence of the fbe gene encoding for a fibrinogen-binding protein in a collection of 107 S. epidermidis strains isolated from orthopaedic infections and 67 from central venous catheter-associated infections. The strains isolated from orthopaedic infections were in large part associated to four different classes of orthopaedic devices, respectively: internal fixation devices, external fixation devices, knee arthroprostheses and hip arthroprostheses. The molecular epidemiology analysis performed by PCR enlightened a statistically significant difference in the prevalence of this adhesion mechanism between orthopaedic infections and catheter-related infections, respectively, of 78% and 91%. The prevalence of fbe ranged from 67% to 91%, suggesting that, even though this adhesin is not strictly necessary for the development of infection, nevertheless it represents a rather common characteristic of strains causing clinical infections, this independently on the presence or the absence of implant materials.