Orthopedic Implant-associated Infections Research Articles

<i>Stenotrophomonas maltophilia</i> as a causative agent of implant-associated infection in trauma and orthopedic patients

Objective. To evaluate an etiologic significance of S. maltophilia in the development of orthopedic implant-associated infections. Materials and methods. The study involved a retrospective analysis of the frequency of excretion of S. maltophilia in patients with periprosthetic infection and osteomyelitis, using the Microbe-2 program in period of 2005–2020. Clinical isolates were excreted according to standard methods. Identification was performed via Microlatest panels using iEMS Reader MF. Antibiotic susceptibility was studied in accordance with EUCAST. Results. Over 16 years 69 strains of S. maltophilia have been identified, comprising 0.33% of all isolated pathogens (n=20631). 50% of isolates were excreted from tissue biopsies, 30% – from wound exudates. In 89% of cases, S. maltophilia was isolated in microbial associations, including 65% of cases together with Grampositive bacteria, 18% with other non-fermenting Gram-negative bacteria, and 6% with other pathogens. 63% appeared sensitive to trimethoprim/sulfamethoxazole and 25.5% of isolates were resistant. The proportion of cultures sensitive to this drug was found to increase from 63% in 2011–2014 to 81% in 2015–2019 (p = 0.08). Conclusion. S. maltophilia should be considered as a causative etiologic agent of severe chronic orthopedic infections.

Role of Dithiothreitol in Detection of Orthopaedic Implant-Associated Infections.

Orthopaedic implant-associated infections (OIAIs) represent a notable complication of contemporary surgical procedures, exerting a considerable impact on patient outcomes and escalating healthcare expenditures. Prompt diagnosis holds paramount importance in managing OIAIs, with sonication widely acknowledged as the preferred method for detecting biofilm-associated infections. Recently, dithiothreitol (DTT) has emerged as a potential substitute for sonication, owing to its demonstrated ability to impede biofilm formation. This study aimed to compare the efficacy of DTT with sonication in identifying microorganisms within implants. Conducted as a prospective cohort investigation, the study encompassed two distinct groups: patients with suspected infections undergoing implant removal (Group A) and those slated for hardware explantation (Group B). Hardware segments were assessed for biofilm-related microorganisms using both sonication and DTT, with a comparative analysis of the two methods. A total of 115 patients were enrolled. In Group A, no statistically significant disparity was observed between DTT and sonication. DTT exhibited a sensitivity of 89.47% and specificity of 96.3%. Conversely, in Group B, both DTT and sonication fluid cultures yielded negative results in all patients. Consequently, this investigation suggests that DTT holds comparable efficacy to sonication in detecting OIAIs, offering a novel, cost-effective, and readily accessible diagnostic modality for identifying implant-associated infections.

Recent Advances in Antibacterial Coatings to Combat Orthopedic Implant-Associated Infections.

Implant-associated infections (IAIs) represent a major health burden due to the complex structural features of biofilms and their inherent tolerance to antimicrobial agents and the immune system. Thus, the viable options to eradicate biofilms embedded on medical implants are surgical operations and long-term and repeated antibiotic courses. Recent years have witnessed a growing interest in the development of robust and reliable strategies for prevention and treatment of IAIs. In particular, it seems promising to develop materials with anti-biofouling and antibacterial properties for combating IAIs on implants. In this contribution, we exclusively focus on recent advances in the development of modified and functionalized implant surfaces for inhibiting bacterial attachment and eventually biofilm formation on orthopedic implants. Further, we highlight recent progress in the development of antibacterial coatings (including self-assembled nanocoatings) for preventing biofilm formation on orthopedic implants. Among the recently introduced approaches for development of efficient and durable antibacterial coatings, we focus on the use of safe and biocompatible materials with excellent antibacterial activities for local delivery of combinatorial antimicrobial agents for preventing and treating IAIs and overcoming antimicrobial resistance.

Recent Progress in antibacterial hydrogel coatings for targeting biofilm to prevent orthopedic implant-associated infections.

The application of orthopedic implants for bone tissue reconstruction and functional restoration is crucial for patients with severe bone fractures and defects. However, the abiotic nature of orthopedic implants allows bacterial adhesion and colonization, leading to the formation of bacterial biofilms on the implant surface. This can result in implant failure and severe complications such as osteomyelitis and septic arthritis. The emergence of antibiotic-resistant bacteria and the limited efficacy of drugs against biofilms have increased the risk of orthopedic implant-associated infections (OIAI), necessitating the development of alternative therapeutics. In this regard, antibacterial hydrogels based on bacteria repelling, contact killing, drug delivery, or external assistance strategies have been extensively investigated for coating orthopedic implants through surface modification, offering a promising approach to target biofilm formation and prevent OIAI. This review provides an overview of recent advancements in the application of antibacterial hydrogel coatings for preventing OIAI by targeting biofilm formation. The topics covered include: (1) the mechanisms underlying OIAI occurrence and the role of biofilms in exacerbating OIAI development; (2) current strategies to impart anti-biofilm properties to hydrogel coatings and the mechanisms involved in treating OIAI. This article aims to summarize the progress in antibacterial hydrogel coatings for OIAI prevention, providing valuable insights and facilitating the development of prognostic markers for the design of effective antibacterial orthopedic implants.

Research progress of phage therapy in orthopedic implant-related infection

The widespread application of implantable materials has brought about a corresponding increase in implant-related complications, with implant-associated infections being the most critical. Biofilms, which often form on these implants, can significantly impede the effectiveness of traditional antibiotic therapies. Therefore, strategies such as surgical removal of infected implants and prolonged antibiotic treatment have been acknowledged as effective measures to eradicate these infections. However,the challenges of antibiotic resistance and biofilm persistence often result in recurrent or hard-to-control infections, posing severe health threats to patients. Recent studies suggest that phages, a type of virus, can directly eliminate pathogenic bacteria and degrade biofilms. Furthermore, clinical trials have demonstrated promising therapeutic results with the combined use of phages and antibiotics. Consequently, this innovative therapy holds significant potential as an effective solution for managing implant-associated infections. This paper rigorously investigates and evaluates the potential value of phage therapy in addressing orthopedic implant-associated infections, based on a comprehensive review of relevant scientific literature.

Antibody-antibiotic conjugate targeted therapy for orthopedic implant-associated intracellular S. aureus infections

IntroductionTreating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. ObjectivesIntroduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. MethodsThe AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. ResultsIn vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. ConclusionsThe application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Long-term antibacterial activity of silver-containing hydroxyapatite coatings against Staphylococcus aureus in vitro and invivo

BackgroundThe potential of silver-containing hydroxyapatite (Ag-HA) coatings to prevent orthopaedic implant-associated infection was explored previously; however, the resistance of Ag-HA coatings to late-onset orthopaedic infections is unknown. This study aimed to evaluate the long-term Ag+ elution and antibacterial properties of the Ag-HA coatings through in vitro and in vivo experiments. MethodsAg-HA-coated disc specimens were immersed in fetal bovine serum (FBS) for six months. Ag concentration was measured over time using inductively coupled plasma-mass spectrometry to evaluate Ag release. The hydroxyapatite (HA)- or Ag-HA-coated disc specimens were immersed in FBS for 3 months to elute Ag+ for in vitro experiments. Methicillin-resistant Staphylococcus aureus (MRSA) suspensions were inoculated onto each disc; after 48 h, the number of colonies and the biofilm volume were measured. HA- or Ag-HA-coated disc specimens were inserted under the skin of Sprague-Dawley rats for three months for in vivo experiments. In in vivo experiment 1, specimens were inoculated with MRSA and the number of colonies was counted after 48 h. In in vivo experiment 2, the specimens were inoculated with bioluminescent S. aureus Xen36 cells, and bioluminescence was measured using an in vivo imaging system. ResultsThe Ag-HA-coated disc specimens continued to elute Ag+ after six months. The biofilm volume in the Ag-HA group was lower than in the HA group. In in vitro and in vivo experiment 1, the bacterial counts in the Ag-HA group were lower than those in the HA group. In in vivo experiment 2, the bioluminescence in the Ag-HA group was lower than that in the HA group on days 1–7 after inoculation. ConclusionsThe Ag-HA-coated discs continued to elute Ag+ for a long period and exhibited antibacterial activity and inhibition of biofilm formation against S. aureus. The Ag-HA coatings have the potential to reduce late-onset orthopaedic implant-associated infections.

The microbiome of orthopedic implant-associated infections and its correlation with inflammatory markers

Background: Implant site and periprosthetic joint infections (PPJI) are of major concern with tremendous improvement in orthopedic operative procedures. Early diagnosis of infection is the cornerstone for success rate and prevention of implant failure. The need for inflammatory biomarkers followed by culture sensitivity remains inevitable in the diagnosis of infection. Aims and Objectives: The aim is to study the prevalent biofilm-forming pathogens and to correlate with antimicrobial resistance and also to estimate inflammatory markers to predict the presence of PPJI. Materials and Methods: A descriptive cross-sectional study involving 57 patients showing signs of PPJI was evaluated. Clinical samples of these cases were processed, the bacterial pathogens were isolated and bio-film formation was tested. Inflammatory markers C-reactive protein by latex agglutination and interleukin-6 (IL6) by ELISA is determined. Results: A total of 36 bacterial pathogens are isolated, 17% are Gram-positive cocci (GPC) and 46% are Gram-negative bacilli (GNB). Among these, 54% are biofilm producers and pseudomonas species (33%) are predominant. Antibiotic susceptibility studies showed GPC to be highly sensitive to linezolid (100%) and vancomycin (100%). Among GNB, pseudomonal species showed susceptibility of 85%, 57%, and 47% to meropenem, amikacin, and piperacillin–tazobactam, respectively. Acinetobacter is the most resistant isolate. The IL value of 19.5 arrived by the receiver operating curve showed maximum sensitivity and minimal false positivity. Conclusion: Assessing the infection-specific biomarkers like IL6 levels is advantageous in earlier detection of implant site infection and aid in instituting specific antibiotics for the most common implant and PPJI before permanent implant failure and sepsis.

Thermosensitive injectable dual drug-loaded chitosan-based hybrid hydrogel for treatment of orthopedic implant infections

A myriad of therapeutic agents and drug delivery systems are available to the surgeons for treating orthopedic implant-associated infections (OIAI), but only very few have demonstrated their effectiveness in preventing bacteria colonization and biofilm formation due to challenges in the local and sustainable therapeutic release. To address this issue, in this work, a thermosensitive injectable hydrogel based on chitosan (CH)-integrated hydroxyapatite nanoparticles (HAP NPs) containing vancomycin (Van) and quercetin (QC)-loaded in F127 micelles (CH-HAP-FQ-Van hydrogel) was fabricated with potential application in the treatment of OIAI. This dual drug delivery system demonstrated a pH-sensitive drug release pattern. In addition, 100 % growth inhibition of Staphylococcus aureus for a duration of 14 days was observed. Apart from the strong antioxidant activities owing to the co-administration of QC even after 432 h, this composite hydrogel revealed 95.88 ± 2.8 % S. aureus biofilm eradication. By consideration of degradation stability (53.52 ± 4.24 %) during 60 days along with smart gelation within 10 min at 37 °C and easy injectability, CH-HAP-FQ-Van hydrogel could be used as a promising ideal local drug delivery system for implant-related infections.

In vitro and in vivo assessment of extended duration cathodic voltage-controlled electrical stimulation for treatment of orthopedic implant-associated infections.

Effective treatment of orthopedic implant-associated infections (IAIs) remains a clinical challenge. The in vitro and in vivo studies presented herein evaluated the antimicrobial effects of applying cathodic voltage-controlled electrical stimulation (CVCES) to titanium implants inoculated with preformed bacterial biofilms of methicillin-resistant Staphylococcus aureus (MRSA). The in vitro studies showed that combining vancomycin therapy (500 µg/mL) with application of CVCES at -1.75 V (all voltages are with respect to Ag/AgCl unless otherwise stated) for 24 h resulted in 99.98% reduction in the coupon-associated MRSA colony-forming units (CFUs) (3.38 × 103 vs. 2.14 × 107 CFU/mL, p < 0.001) and a 99.97% reduction in the planktonic CFU (4.04 × 104 vs. 1.26 × 108 CFU/mL, p < 0.001) as compared with the no treatment control samples. The in vivo studies utilized a rodent model of MRSA IAIs and showed a combination of vancomycin therapy (150 mg/kg twice daily) with CVCES of -1.75 V for 24 h had significant reductions in the implant associated CFU (1.42 × 101 vs. 1.2 × 106 CFU/mL, p < 0.003) and bone CFU (5.29 × 101 vs. 4.48 × 106 CFU/mL, p < 0.003) as compared with the untreated control animals. Importantly, the combined 24 h CVCES and antibiotic treatments resulted in no implant-associated MRSA CFU enumerated in 83% of the animals (five out of six animals) and no bone-associated MRSA CFU enumerated in 50% of the animals (three out of six animals). Overall, the outcomes of this study have shown that extended duration CVCES therapy is an effective adjunctive therapy to eradicate IAIs.

Shotgun sequencing of sonication fluid for the diagnosis of orthopaedic implant-associated infections with Cutibacterium acnes as suspected causative agent.

Orthopaedic implant-associated infections (OIAIs) due to Cutibacterium acnes can be difficult to diagnose. The aim of this pilot study was to determine if metagenomic next-generation sequencing (mNGS) can provide additional information to improve the diagnosis of C. acnes OIAIs. mNGS was performed on sonication fluid (SF) specimens derived from 24 implants. These were divided into three groups, based on culture results: group I, culture-negative (n = 4); group II, culture-positive for C. acnes (n = 10); and group III, culture-positive for other bacteria (n = 10). In group I, sequence reads from C. acnes were detected in only one SF sample, originating from a suspected case of OIAIs, which was SF and tissue culture-negative. In group II, C. acnes sequences were detected in 7/10 samples. In group III, C. acnes sequence reads were found in 5/10 samples, in addition to sequence reads that matched the bacterial species identified by culture. These samples could represent polymicrobial infections that were missed by culture. Taken together, mNGS was able to detect C. acnes DNA in more samples compared to culture and could be used to identify cases of suspected C. acnes OIAIs, in particular regarding possible polymicrobial infections, where the growth of C. acnes might be compromised due to a fast-growing bacterial species. However, since SF specimens are usually low-biomass samples, mNGS is prone to DNA contamination, possibly introduced during DNA extraction or sequencing procedures. Thus, it is advisable to set a sequence read count threshold, taking into account project- and NGS-specific criteria.

Clinical Features and Outcomes of Enterococcal Bone and Joint Infections and Factors Associated with Treatment Failure over a 13-Year Period in a French Teaching Hospital.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

Can Differently Stabilized Silver Nanoparticles Modify Calcium Phosphate Precipitation?

Calcium phosphates (CaPs) composites with silver nanoparticles (AgNPs) attract attention as a possible alternative to conventional approaches to combating orthopedic implant-associated infections. Although precipitation of calcium phosphates at room temperatures was pointed out as an advantageous method for the preparation of various CaP-based biomaterials, to the best of our knowledge, no such study exists for the preparation of CaPs/AgNP composites. Motivated by this lack of data in this study we investigated the influence of AgNPs stabilized with citrate (cit-AgNPs), poly(vinylpyrrolidone) (PVP-AgNPs), and sodium bis(2-ethylhexyl) sulfosuccinate (AOT-AgNPs) in the concentration range 5-25 mg dm-3 on the precipitation of CaPs. The first solid phase to precipitate in the investigated precipitation system was amorphous calcium phosphate (ACP). The effect of AgNPs on ACP stability was significant only in the presence of the highest concentration of AOT-AgNPs. However, in all precipitation systems containing AgNPs, the morphology of ACP was affected, as gel-like precipitates formed in addition to the typical chain-like aggregates of spherical particles. The exact effect depended on the type of AgNPs. After 60 min of reaction time, a mixture of calcium-deficient hydroxyapatite (CaDHA) and a smaller amount of octacalcium phosphate (OCP) formed. PXRD and EPR data point out that the amount of formed OCP decreases with increasing AgNPs concentration. The obtained results showed that AgNPs can modify the precipitation of CaPs and that CaPs properties can be fine-tuned by the choice of stabilizing agent. Furthermore, it was shown that precipitation can be used as a simple and fast method for CaP/AgNPs composites preparation which is of special interest for biomaterials preparation.

In vitro elution characteristics of antibiotic-loaded polymethylmethacrylate cement and a calcium sulfate bone substitute using staphylococci isolated from orthopedic implant-associated infections.

Polymethylmethacrylate (PMMA) remains the gold standard antibiotic carrier in the management of osteomyelitis. However, biodegradable ceramic carriers may exhibit more efficient antibiotic elution properties. Through zone of inhibition (ZOI) testing and biofilm killing assays, we assessed the in vitro elution efficacy of vancomycin released from calcium sulfate (PG-CSH) and PMMA beads as carriers on clinical strains of Staphylococcus aureus and Staphylococcus epidermidis, which were isolated from sonication fluid of orthopedic implant-associated infections. Overall, vancomycin-loaded PMMA and PG-CSH beads showed potency (ZOI above 4cm2 ) for up to 14 days against ATCC and clinical strains. Vancomycin-loaded PG-CSH beads displayed higher rates, exhibited a more stable antibiotic elution, had greater impacts on bacterial colony-forming unit counts and produced higher ZOIs; additionally, statistically significant differences (Student's t test) were observed in different time sets during the experiment. In the biofilm killing assay, PG-CSH loaded with vancomycin resulted in more bacterial deaths. In conclusion, in the present study, both PG-CSH and PMMA beads acted as good carriers, but greater antimicrobial elution and biofilm bacterial killing were observed with PG-CSH than PMMA. Future in vitro research should focus on testing other difficult-to-treat clinical strains, including multidrug resistant coagulase-negative staphylococci and Gram-negative bacilli.

Graphene and its derivatives: "one stone, three birds" strategy for orthopedic implant-associated infections.

Orthopedic implants provide an avascular surface for microbial attachment and biofilm formation, impeding the entry of immune cells and the diffusion of antibiotics. The above is an important cause of dental and orthopedic implant-associated infection (IAI). For the prevention and treatment of IAI, the drawbacks of antibiotic resistance and surgical treatment are increasingly apparent. Due to their outstanding biological properties such as biocompatibility, immunomodulatory effects, and antibacterial properties, graphene-based nanomaterials (GBNs) have been applied to bone tissue engineering to deal with IAI, and in particular have great potential application in drug/gene carriers, multi-functional platforms, and coating forms. Here we review the latest research progress and achievements in GBNs for the prevention and treatment of IAI, mainly including their biomedical applications for antibacterial and immunomodulation effects, and for inducing osteogenesis. Furthermore, the biosafety of graphene family materials in bone tissue regeneration and the feasibility of clinical application are critically analyzed and discussed.

Biofilm formation and inflammatory potential of Staphylococcus saccharolyticus: A possible cause of orthopedic implant-associated infections.

Staphylococcus saccharolyticus, a coagulase-negative staphylococcal species, has some unusual characteristics for human-associated staphylococci, such as slow growth and its preference for anoxic culture conditions. This species is a relatively abundant member of the human skin microbiota, but its microbiological properties, as well as the pathogenic potential, have scarcely been investigated so far, despite being occasionally isolated from different types of infections including orthopedic implant-associated infections. Here, we investigated the growth and biofilm properties of clinical isolates of S. saccharolyticus and determined host cell responses. Growth assessments in anoxic and oxic conditions revealed strain-dependent outcomes, as some strains can also grow aerobically. All tested strains of S. saccharolyticus were able to form biofilm in a microtiter plate assay. Strain-dependent differences were determined by optical coherence tomography, revealing that medium supplementation with glucose and sodium chloride enhanced biofilm formation. Visualization of the biofilm by confocal laser scanning microscopy revealed the role of extracellular DNA in the biofilm structure. In addition to attached biofilms, S. saccharolyticus also formed bacterial aggregates at an early stage of growth. Transcriptome analysis of biofilm-grown versus planktonic cells revealed a set of upregulated genes in biofilm-embedded cells, including factors involved in adhesion, colonization, and competition such as epidermin, type I toxin-antitoxin system, and phenol-soluble modulins (beta and epsilon). To investigate consequences for the host after encountering S. saccharolyticus, cytokine profiling and host cell viability were assessed by infection experiments with differentiated THP-1 cells. The microorganism strongly triggered the secretion of the tested pro-inflammatory cyto- and chemokines IL-6, IL-8, and TNF-alpha, determined at 24 h post-infection. S. saccharolyticus was less cytotoxic than Staphylococcus aureus. Taken together, the results indicate that S. saccharolyticus has substantial pathogenic potential. Thus, it can be a potential cause of orthopedic implant-associated infections and other types of deep-seated infections.

In situ precipitated hydroxyapatite-chitosan composite loaded with ciprofloxacin: Formulation, mechanical, in vitro antibiotic uptake, release, and antibacterial properties

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites loaded with ciprofloxacin antibiotic (HA–CS–CIP) were formulated using the in situ and the solid-liquid method coupled with the freeze-drying process. The interaction of the HA-CS composite powder and ciprofloxacin antibiotic (CIP) was investigated by batch adsorption essays. The kinetic and the isotherm data were fitted well to the pseudo-second-order and Freundlich models, respectively. The compressive strength of the HA-CS composite was increased by 7-fold and 10-fold when using respectively 15 wt% and 30 wt% of the polymer compared to the HA-CS5 formulation (3.6 ± 0.7 MPa) made only from HA powder and CS gel (5 wt%). However, this parameter decreased from 36.8 ± 8.5 MPa down to 20.5 ± 4.7 MPa when the antibiotic content increased from 0 up to 9 wt%, respectively. The in vitro release results showed a sustained and controlled CIP release for up to 10 days. The release data fitting and modeling indicate that the process follows a Fickian diffusion mechanism. Also, the formulated composite revealed an antibacterial effect against Staphylococcus aureus and Escherichia coli bacteria. The developed composite may be a promising candidate for bone substitution and as an antibiotic local delivery system for the treatment of orthopedic implant-associated infections.

Design, Characterization, and Antibacterial Performance of MAPLE-Deposited Coatings of Magnesium Phosphate-Containing Silver Nanoparticles in Biocompatible Concentrations.

Bone disorders and traumas represent a common type of healthcare emergency affecting men and women worldwide. Since most of these diseases imply surgery, frequently complicated by exogenous or endogenous infections, there is an acute need for improving their therapeutic approaches, particularly in clinical conditions requiring orthopedic implants. Various biomaterials have been investigated in the last decades for their potential to increase bone regeneration and prevent orthopedic infections. The present study aimed to develop a series of MAPLE-deposited coatings composed of magnesium phosphate (Mg3(PO4)2) and silver nanoparticles (AgNPs) designed to ensure osteoblast proliferation and anti-infective properties simultaneously. Mg3(PO4)2 and AgNPs were obtained through the cooling bath reaction and chemical reduction, respectively, and then characterized through X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Selected Area Electron Diffraction (SAED). Subsequently, the obtained coatings were evaluated by Infrared Microscopy (IRM), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (SEM). Their biological properties show that the proposed composite coatings exhibit well-balanced biocompatibility and antibacterial activity, promoting osteoblasts viability and proliferation and inhibiting the adherence and growth of Staphylococcus aureus and Pseudomonas aeruginosa, two of the most important agents of orthopedic implant-associated infections.

Characteristics of the immune microenvironment and related treatment strategies in patients with periprosthetic joint infection

Periprosthetic joint infection (PJI) involves complex immunomodulatory interactions between pathogens,biomaterials,and hosts,and correlates with alterations in the ratio of immune cells as well as in the concentration of immune checkpoint molecules.Prosthesis,biofilm,microorganisms,and host constitute a special and complex immune microenvironment.Fully studying the characteristics of immune microenvironment and potential targets of immunotherapy in orthopedic implant-associated infections are expected to provide a new direction for clinical treatment of PJI. An overview of the literature related to PJI and immune regulation at domestic and international sites was conducted to summarize and analyze the characteristics of the immune microenvironment and the potential value of related immunotherapy, aiming to provide new insights for the targeted treatment of PJI.

Comparative Phenotypic and Genomic Features of Staphylococci from Sonication Fluid of Orthopedic Implant-Associated Infections with Poor Outcome.

Staphylococcus spp. remain the leading biofilm-forming agents causing orthopedic implant-associated infections (OIAI). This is a descriptive study of phenotypic and genomic features identified in clinical isolates of S. aureus and coagulase-negative Staphylococcus (CoNS) recovered from OIAIs patients that progressed to treatment failure. Ten isolates were identified by matrix-time-of-flight laser-assisted desorption mass spectrometry (MALDI-TOF-MS) and tested for antibiotic susceptibility and biofilm formation. Genotypic characteristics, including, MLST (Multi Locus Sequence Typing), SCCmec typing, virulence and resistance genes were assessed by whole-genome sequencing (WGS). All S. aureus harbored mecA, blaZ, and multiple resistance genes for aminoglycosides and quinolones. All MRSA were strong biofilm producers harboring the complete icaADBC and icaR operon. Seven CoNS isolates comprising five species (S. epidermidis, S. haemolyticus, S. sciuri, S. capitis and S. lugdunensis) were analyzed, with mecA gene detected in five isolates. S. haemolitycus (isolate 95), and S. lugdunensis were unable to form biofilm and did not harbor the complete icaADBCR operon. High variability of adhesion genes was detected, with atl, ebp, icaADBC operon, and IS256 being the most common. In conclusion, MRSA and CoNS isolates carrying genes for biofilm production, and resistance to β-lactam and aminoglycosides are associated with treatment failure in OIAIs.