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Background: Artificial intelligence chatbot tools responses might discern patterns and correlations that may elude human observation, leading to more accurate and timely interventions. However, their reliability to answer healthcare-related questions is still debated. This study aimed to assess the performance of the three versions of GPT-based chatbots about prosthetic joint infections (PJI). Methods: Thirty questions concerning the diagnosis and treatment of hip and knee PJIs, stratified by a priori established difficulty, were generated by a team of experts, and administered to ChatGPT 3.5, BingChat, and ChatGPT 4.0. Responses were rated by three orthopedic surgeons and two infectious diseases physicians using a five-point Likert-like scale with numerical values to quantify the quality of responses. Inter-rater reliability was assessed by interclass correlation statistics. Results: Responses averaged "good-to-very good" for all chatbots examined, both in diagnosis and treatment, with no significant differences according to the difficulty of the questions. However, BingChat ratings were significantly lower in the treatment setting (p = 0.025), particularly in terms of accuracy (p = 0.02) and completeness (p = 0.004). Agreement in ratings among examiners appeared to be very poor. Conclusions: On average, the quality of responses is rated positively by experts, but with ratings that frequently may vary widely. This currently suggests that AI chatbot tools are still unreliable in the management of PJI. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials. [ABSTRACT FROM AUTHOR]

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first‐line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug‐resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone–implant interface. [ABSTRACT FROM AUTHOR]

Zhouyang Hu,1,2,&ast; Xiaobing Yin,3,&ast; Guoxin Fan,1,2 Xiang Liao1,2 1Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoxin Fan; Xiang Liao, Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China, Tel +86-18529093630 ; +86-13725595056, Email fan06309@163.com; liaoxiang75@email.szu.edu.cnObjective: Bibliometric analysis is commonly used to visualize the knowledge foundation, trends, and patterns in a specific scientific field by performing a quantitative evaluation of the relevant literature. The purpose of this study was to perform a bibliometric analysis of recent studies in the field of orthopedic biofilm research and identify its current trends and hotspots.Methods: Research studies were retrieved from the Web of Science Core Collection and Scopus databases and analyzed in bibliometrix with R package (4.2.2).Results: A total of 2426 literature were included in the study. Journal of orthopaedic research and Clinical orthopaedics and related research ranked first in terms of productivity and impact, with 57 published articles and 32 h-index, respectively. Trampuz A, Ohio State Univ and the United States ranked as the most productive authors, institutions, and countries. Biofilm formation, role of sonication, biomaterial mechanism and antibiotic loading have been investigated as the trend and hotspots in the field of orthopedic biofilm research.Conclusion: This study provides a thorough overview of the state of the art of current orthopedic biofilm research and offers valuable insights into recent trends and hotspots in this field.Keywords: biofilm, orthopedic infection, bibliometric analysis, hotspot, research trend

Sifeng Shi, Weiran Shi, Bing Zhou, Shang Qiu Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Sifeng Shi, Email shisifeng20071@163.com; Shang Qiu, Email shangqiu20132@163.comAbstract: Orthopedic infection is one of the most intractable orthopedic problems. Bacteria resistant to antibiotics also develop gradually. Chitosan is widely used in the Biomedical field because of its high biocompatibility, biodegradability, and antibacterial activity. Chitosan-based drug delivery systems are frequently utilized to produce controlled medication release. When combined with antibiotics, synergistic antibacterial effects can be achieved. Chitosan-based nanoparticles are one of the most widely used applications in drug delivery systems. The focus of this review is to provide information on new methods being developed for chitosan-based nanoparticles in the field of bone infection treatment, including chitosan nanoparticles for antibacterial purposes, Ch-loaded with antibiotics, Ch-loaded with metal, and used as immune adjuvants. It may Provide ideas for the fundamental research and the prospects of future clinical applications of orthopedic infections.Keywords: chitosan nanoparticles, orthopedic infection, chitosan-based nanoparticles, staphylococcus aureus

Boyong Wang,1,&ast; Qiaojie Wang,1,&ast; Mingzhang Li,1 Jinlong Yu,1 Feng Jiang,1 Yujie Hu,1 Geyong Guo,1 Xiaohua Chen,2 Jin Tang,3 Pei Han,1 Hao Shen1 1Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Department of Infectious Diseases, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 3Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Shen, Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China, Email shenhao7212@sina.comObjective: The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.Methods: The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.Results: Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.Conclusion: mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.Importance: TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.Keywords: metagenomic next-generation sequencing, implant-associated infection, Mycobacterium tuberculosis complex, orthopedic infection, diagnosis

Introduction: Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection. Methods: Hospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR. Results and discussion: A total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection (P < 0.001). S. aureus was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for P. aeruginosa and K. pneumoniae, possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, P = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment. [ABSTRACT FROM AUTHOR]

Background. The number of surgeries on the musculoskeletal system is increasing every year. Along with the increasing access to orthopedic care, the number of patients with orthopedic infection, the etiological agents of which can be from various taxonomic groups, is also increasing. Staphylococcus aureus and different types of coagulase-negative staphylococci (CoNS), including S. epidermidis and S. lugdunensis, together are the causative agents in 70% of cases. Aim of the study — to analyze the dynamics of the microbial spectrum isolated from patients of the septic surgery department for the period from 2011 to 2022. Methods. We performed a retrospective analysis of the microbial spectrum isolated from patients who were treated in the septic surgery department from January 1, 2011 to December 31, 2022. The leading pathogens were microorganisms whose share in the spectrum exceeded 3.5%. Of the isolated pathogens, 48.8% were the only etiological agents, and microbial associations were detected in 51.2% of the isolated pathogens. Results. A total of 10,327 bacteria strains were identified over the 12-year period. The leading microorganisms causing orthopedic infection were Staphylococcus spp., Enterococcus spp., Propionibacterium spp., Pseudomonas aeruginosa, Corynebacterium spp., Streptococcus spp., Klebsiella spp. and Acinetobacter spp. In the dynamics of isolated pathogens during the analyzed period, several trends were determined: a decrease in the shares of S. aureus, Enterococcus spp., P. aeruginosa, Acinetobacter spp. and an increase in the shares of CoNS and Corynebacterium spp. Conclusion. During 12 years, in the microbial spectrum of orthopedic infection in patients of the septic surgery department of our Center, Gram-positive bacteria, in the majority representatives of the genus Staphylococcus, prevailed. At the same time, a significant decrease in the share of S. aureus strains and an increase in the frequency of isolation of various species of CoNS were registered. A significant decrease in the number of non-fermenting Gram-negative bacteria was also revealed.

Introduction Polymethyl methacrylate (PMMA) is a common depot system in the treatment of chronic osteomyelitis. However, a lot of its shortcomings do not allow us to consider it ideal. Purpose of the work was to study in vivo the effectiveness of a polymer hydrogel containing an antibiotic for chronic osteomyelitis of the tibia in a rabbit model and compare it with PMMA Materials and methods The study was performed on the lower leg of 25 mature Chinchilla rabbits. A model of chronic osteomyelitis of the tibia was created. A methicillin-sensitive strain of Staphylococcus aureus (MSSA), highly active against cefazolin, was chosen as an infectious agent. Surgical debridement started 21 days after the clinical, laboratory, radiological and microbiological confirmation of the diagnosis, the technique for all animals was the same. The experimental group (n = 11) was treated by implantation of a polymer hydrogel, the comparison group (n = 11) with PMMA, and the control group (n = 3) had no implanted substance. In the postoperative period, monitoring of the local status, weight and body temperature of the animals, microbiological and radiological studies were carried out. Animals were taken out of the experiment by stages. Biopsies were sent for bacteriological and histomorphometric studies. Statistical comparison of the groups was performed using the Mann ‑ Whitney, Kruskell ‑ Wallis and Tukey criteria, descriptive statistics were used for the control group. Results In the experimental group, in all cases, postoperative wounds healed in a timely manner, the levels of WBC and CRP significantly (p = 0.040) decreased from 14 and 21 days, respectively. Microbiologically, the growth of microflora from the wound discharge and biopsy specimens was not detected; radiographic progression of chronic osteomyelitis was not observed; histomorphometry revealed a significant (p = 0.002) effective relief of the inflammatory process. In the comparison group, systemic antibiotic therapy was required from postoperative day 7. Levels of inflammatory markers decreased less effectively than in the experimental group. MSSA was verified from wound discharge and biopsy specimens at almost every follow-up time-point. X-rays and histomorphometry (p = 0.001), on average, detected exacerbation of osteomyelitis. In the control group, systemic therapy did not give positive dynamics. Discussion A comparative analysis showed that the hydrogel impregnated with an antibacterial agent, unlike PMMA, reliably arrests chronic osteomyelitis without auxiliary systemic antibiotic therapy and does not cause material-associated bone resorption. The clinical and laboratory picture is fully consistent with the data of microbiology, radiology and histomorphometry. Conclusion Hydrogel impregnated with an antibiotic reliably and effectively stops chronic osteomyelitis compared to PMMA.

Introduction Mycobacterium abscessus species belongs to the group of non-tuberculosis mycobacteria responsible for chronic infections in people with weakened immunity. M. abscessus exist in various ecological niches and are able to colonize artificial surfaces, including medical and surgical instruments/ devices. Due to the low incidence of M. abscessus as a causative agent of orthopedic infection, a rare clinical case of periprosthetic infection caused by M. abscessus would interest practitioners. The aim is to present a clinical case of periprosthetic infection caused by M. abscessus. Materials and methods From the medical records and discharge documents, it was known that female patient X. underwent total hip replacement at her residence hospital. Signs of acute infection of the postoperative wound appeared in the early postoperative period. Results Three months later, the patient was hospitalized in a specialized institution with a diagnosis of chronic deep periprosthetic infection. During the examination, the mycobacterial etiology of the process was established. During two hospitalizations, the patient underwent 4 consecutive revision surgeries (including muscle plastic surgery and installation of an antimicrobial spacer) and massive parenteral antibiotic therapy for 8 months, including at the outpatient stage, using at least 3 antibacterial agents. After 4 years, the patient does not complain of the infectious process. Postoperative scar is 45 cm. The residual shortening of the right lower limb of 3 cm was compensated by orthopedic shoes. Discussion Treatment of infection caused by M. abscessus is challenging due to the natural resistance of the pathogen to a wide range of antibacterial drugs. The literature describes separate cases of orthopedic infections caused by this pathogen. All authors agree that the key to successful treatment is a combination of radical surgical debridement and antibacterial therapy using at least three antimicrobial drugs. Conclusion A rare clinical case of periprosthetic infection caused by Mycobacterium abscessus after primary hip replacement is presented. This infectious agent is a rare pathogen, for which there is no proven therapeutic algorithm. Long-term aggressive antibiotic therapy in combination with stage-by-stage surgical treatment was successful.

Staphylococcus aureus (S. aureus) has the ability to invade human cortical bones and cause intracellular infections in osteoblasts, which may lead to a long-term infection that is difficult to eliminate. It is critical to identify the underlying mechanisms of the osteoblast response to the intracellular S. aureus. More recently, multiple circular RNA (circRNA) functions have been identified, including serving as protein scaffolds or miRNA sponges and being translated into polypeptides. The role that circRNAs play in intracellular S. aureus infection of osteoblasts has not, to our knowledge, been investigated. Here, we established an intracellular infection model of S. aureus in osteoblasts and compared the circRNA expression of osteoblasts between the infected and control groups using RNA sequencing technology, by which a significant difference was found. In total, 117 upregulated and 125 down-regulated differentially expressed circRNAs (DEcircRNAs) were identified, and reverse transcription-quantitative PCR was employed to validate the results of RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that DEcircRNAs were enriched in processes associated with macromolecule modification, cellular component organization or biogenesis, and intracellular non-membrane-bound organelles. Finally, a potentially important network of circRNA-miRNA-mRNA based on the DEcircRNAs was constructed. Overall, this study revealed the circRNA expression profile of human osteoblasts infected by intracellular S. aureus for the first time, and identified the circRNAs that may contribute to the pathogenesis of infectious diseases caused by intracellular S. aureus infection in human osteoblasts.

Osteoarticular infections (OAI) are a significant cause of morbidity and mortality. Cultures and serology are some of the gold standards for identifying infection but are often unable to provide a timely diagnosis or a diagnosis at all. Genetic testing offers capabilities that other modalities lack. Polymerase chain reaction has multiple versions with various costs and turnaround times. This technology has become implemented in multiple pediatric center OAI diagnostic protocols. There is sufficient literature documenting effectiveness in certain clinical situations, especially with fastidious organism diagnosis, but significant limitation still exists. Metagenomic next-generation sequencing is an unbiased or hypothesis-free modality with the capability to detect the genetic material of bacteria, viruses, parasites, fungi, and humans from a single sample. Potential benefits include pathogen identification unaffected by antimicrobial administration, detection of fastidious organisms more quickly, delineation of pathogens in polymicrobial infections, antimicrobial susceptibility, and avoidance of invasive procedures. It is a resource-intensive modality with little standardization of the complex processes. Appropriate use and definitive clinical impact have yet to be determined.

Background: Multispecies biofilm orthopedic infections are more challenging to treat than mono-species infections. In this in-vitro study, we aimed to determine if a multispecies biofilm, consisting of Gram positive and negative species with different antibiotic susceptibilities could be treated more effectively using high purity antibiotic-loaded calcium sulfate beads (HP-ALCSB) containing vancomycin (VAN) and tobramycin (TOB) in combination than alone. Methods: Three sets of species pairs from bioluminescent strains of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) and clinical isolates, Enterococcus faecalis (EF) and Enterobacter cloacae were screened for compatibility. PA + EF developed intermixed biofilms with similar cell concentrations and so were grown on 316L stainless steel coupons for 72 h or as 24 h agar lawn biofilms and then treated with HP-ALCSBs with single or combination antibiotics and assessed by viable count or bioluminescence and light imaging to distinguish each species. Replica plating was used to assess viability. Results: The VAN + TOB bead significantly reduced the PA + EF biofilm CFU and reduced the concentration of surviving antibiotic tolerant variants by 50% compared to single antibiotics. Conclusions: The combination of Gram-negative and positive targeted antibiotics released from HP-ALCSBs may be more effective in treating multispecies biofilms than monotherapy alone. [ABSTRACT FROM AUTHOR]

Background:Staphylococcus lugdunensis is a coagulase-negative staphylococci that is considered normal skin microbiota. It has been described as a cause of soft tissue infections but is not a common micro-organism as the cause of orthopedic surgery-related infections. This study describes the characteristics, treatment, and results of musculoskeletal infection by Staphylococcus lugdunensis treated in our institution. Methods: We performed a descriptive, retrospective observational study. Clinical records of all musculoskeletal infections treated in our department between 2012 and 2020 were reviewed. We selected those patients with a positive monomicrobial culture for Staphylococcus lugdunensis. Risk factors for infection, patient's medical records, previous surgery performed, time from surgery to infection, culture antibiogram, antibiotic and surgical treatment for the infection, and recovery rate were registered for the analysis. Results: Of the 1,482 patients with musculoskeletal infections diagnosed in our institution, 22 had a monomicrobial positive culture of Staphylococcus lugdunensis after an orthopedic surgery representing 1.5% of all orthopedic infections. Ten patients underwent arthroplasty, six underwent fractures synthesis, three had foot surgeries, two had anterior cruciate ligament reconstructions, and one had spine surgery. All patients needed surgery and antibiotic treatment with a mean of two surgeries. The most used antibiotic scheme was levofloxacin-rifampicin. The mean follow-up was 36 months. Ninety-six percent of the patients achieved a complete clinical and analytical recovery. Conclusions: Although musculoskeletal infections caused by Staphylococcus lugdunensis are not common, we have observed a statistically significant incidence increase of Staphylococcus lugdunensis in recent years. If managed with appropriately aggressive surgical treatment and correct antibiotic therapy, good results can be obtained. [ABSTRACT FROM AUTHOR]

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections, impenetrable microbial biofilms, and irreversible antibiotic resistance. In the past, the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host's immune response. Inspired by the clearance of infection by the innate neutrophil response and participation in anti-infectious immunity of Zn ions, we report an innovative neutrophil extracellular traps (NETs) strategy, induced by biodegradable pure Zn, which achieved therapeutic efficacy toward biomaterial-related infections. Our in vitro and in vivo data showed that pure Zn was favorable for NETs formation by promoting the release of DNA fibers and granule proteins in a reactive oxygen species (ROS)-dependent manner, thereby retraining and degrading bacteria with an efficiency of up to 99.5%. Transcriptome analysis revealed that cytoskeletal rearrangement and toll-like receptor (TLR) signaling pathway were also involved in Zn-induced NETs formation. Furthermore, the in vivo results of a Staphylococcus aureus (S. aureus)-infected rat model verified that pure Zn potentiated the bactericidal capability of neutrophils around implants, and promoted osseointegration in S. aureus-infected rat femurs. This antibacterial immunity concept lays a foundation for the development of other antibacterial biomaterials and holds great promise for treating orthopedic infections.

Purpose To evaluate the results of a comparative analysis of the in vitro antimicrobial activity of polymer hydrogels and PMMA impregnated with antibiotics against test cultures of the leading pathogens of bone infection. Materials and methods A comparative analysis of the antimicrobial activity of the polymer hydrogel and PMMA impregnated with antibiotics was carried out. The bactericidal efficacy and prolongation of action of the following microbe-antibiotic pairs were assessed: MSSA – gentamicin, MSSE – cefazolin, MRSA and MRSE – vancomycin, A. baumannii – tobramycin. The duration of the study is 7 days. Statistical comparison of groups was carried out using the Mann-Whitney and Wilcoxon tests; the median and 95 % CI were used to describe the data. Results The obtained indicators of the zone of inhibition of the growth of microorganisms around the polymer hydrogel were several times higher than the results of PMMA (p < 0.05 for all periods). The antimicrobial activity of hydrogels in all cases lasted more than 7 days. Hydrogels impregnated with vancomycin showed the lowest rate of contraction of the inhibition zone. The best antimicrobial effect was demonstrated by the compared samples with cefazolin in relation to MSSE, the maximum index of the zone of suppression of which, on average, for the hydrogel was 29.3 mm, PMMA – 22.3 mm. Discussion Samples from polymer hydrogel impregnated with antibiotics demonstrated prolonged pronounced effective antimicrobial activity against the leading pathogens of orthopedic infections in comparison with PMMA. The bactericidal efficacy of the polymer hydrogel significantly exceeded the activity of PMMA already from the first day of the study (p = 0.002). The action of the hydrogel throughout the study was uniform without abrupt changes or dips (p > 0.05), in contrast to bone cement, whose activity against all test cultures significantly decreased (p = 0.042) on the 2nd day of the study. Conclusion Polymeric biodegradable hydrogels impregnated with antibiotics have a greater antimicrobial potential compared to PMMA. Uniform, slow and controlled release of the drug and effective inhibition of the growth of microorganisms, as well as prolonged action show that these properties may turn hydrogels into an effective depot system.

Objective. To study effects of bacteriophages on biofilm formation and formed biofilm by S. aureus isolated from patients with orthopedic infection. Materials and Methods. A total of 50 clinical strains of S. aureus were tested. Species identification was performed by MALDI-TOF MS, antibiotic susceptibility – in accordance with the EUCAST v21. Isolates susceptibility to bacteriophages «Sextafag» (Microgen, Russia) was determined by MPA medium. The antibacterial activity of phages against S. aureus ATCC 29213 and S. aureus ATCC 43300 was evaluated by growth kinetic curves. Biofilms of bacteriophage-sensitive S. aureus strains were formed according to the protocol described by O’Toole. Isolates were divided into categories in accordance with the Stepanovic criteria. The effects of bacteriophages on the formation of S. aureus biofilm were studied by co-incubation of phages and bacteria followed by calculation of the percentage inhibition relative to the control without the introduction of the phages. The effect of phages on 24-hour biofilms formed by staphylococci was also evaluated in comparison with the control. Results. Out of 50 clinical S. aureus strains studied, 43 isolates (86%) were susceptible to phages, including 22 MSSA and 21 MRSA. All phage-susceptible cultures were characterized by biofilm-forming ability of varying degree: 28% – weak biofilm producer, 35% – moderate, 37% – strong. Inhibition of biofilm formation was determined in all tested MRSA strains, while in 73% of isolates the index of biofilm formation inhibition was more than 80%, which exceeded this indicator for MSSA by 2.5 times. In turn, the destruction of the formed biofilm under the action of the bacteriophage was 72% for all S. aureus. In 57% of MSSA strains, the decrease in biofilm biomass in comparison with the control was more than 80%, while this indicator was 2 times higher than for MRSA. Conclusions. The results demonstrated a high in vitro efficacy of bacteriophages against biofilm formation in S. aureus.

The increasing prevalence of antibiotic-resistant bacterial infections has led to the search for new approaches. This study aimed to evaluate the effects of carvacrol and N-acetyl cysteine, both individually and in combination, on the planktonic cells and biofilm formations of Staphylococcus aureus , including methicillin-resistant and methicillin-sensitive strains. Additionally, the study sought to perform cytotoxicity tests and chemical characterization to further understand the properties and potential applications of these substances. A total of 19 S. aureus strains were included in the study. Minimum inhibitory concentration and minimum bactericidal concentration were determined by assays. Synergy analysis tests were carried out. Cytotoxicity tests were conducted on the fibroblast cell line. Characterization test was performed. While Minimum inhibitory concentration and minimum bactericidal concentration values for carvacrol varied between 250 and 500 μg/ml, these values were in the range of 32–64 mg/ml for N-acetyl cysteine. Biofilm formation activities were identified. A total of eight strains, including six clinical and two standard strains with the highest biofilm-forming ability, were selected for combination studies. The combination of Carvacrol and N-acetyl cysteine exhibited synergistic and partially synergistic effects on the tested planktonic and biofilm strains, and these effects were dose-dependent. Carvacrol was found to be the most active drug at the end of 24, 48, and 72 h. Regarding the synergistic effect of N-acetyl cysteine + carvacrol, it was revealed to exhibit higher activity than N-acetyl cysteine and lower activity than carvacrol. The combination of carvacrol and N-acetyl cysteine demonstrated synergistic and partially synergistic effects against both planktonic and biofilm forms of Staphylococcus aureus. These results suggest potential for novel approaches in managing orthopedic infections, warranting further research to explore their therapeutic applications. • The CAR and NAC combination inhibits MRSA biofilm formation. • The NAC + CAR combination balances efficacy and safety for infections. • The study provides insights into the antimicrobial mechanisms of NAC and CAR through detailed chemical analysis. [ABSTRACT FROM AUTHOR]

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) is increasingly recognized as superior to conventional imaging methods for diagnosing osteomyelitis in foals. However, comprehensive studies in this area are limited. This study aims to report on clinical cases of osteomyelitis in foals, establishing a relationship between CT findings and survival outcomes. Additionally, it compares CT imaging with conventional methods such as radiography and ultrasound. We hypothesized that CT variables would more accurately predict survival than other clinical factors and provide more detailed information about osteomyelitis lesions. This retrospective study included foals presenting at a single equine referral hospital between July 2019 and December 2022. Inclusion criteria were: (1) foals less than 9 months of age, (2) presumptive clinical diagnosis of osteomyelitis, and (3) CT examination for further evaluation. Forty-four foals met the criteria; 29 (66%) survived to discharge, and 23 (55%) had long-term survival. Key variables associated with survival included joint collapse (P = .011, OR, 0.054, 95% CI, 0.006-0.506) and lesions in multiple locations (P = .015, OR, 0.19, 95% CI, 0.05-0.7). In 93% of cases, CT examination modified the diagnosis, revealing improved lesion localization (72%), lesion size (76%), or detecting additional lesions (45%). Common lesions involved the axial and proximal appendicular skeletons, with 8 foals (18%) having only axial skeleton involvement and 5 (11%) presenting with both axial and appendicular lesions. Coxofemoral joint involvement was diagnosed in 12 foals (27%), while pelvic lesions were found in 8 (18%). These findings underscore the critical role of CT in identifying and localizing complex lesions, ultimately improving prognostic assessments., (© 2024 American College of Veterinary Radiology.)

Background: Multispecies biofilm orthopedic infections are more challenging to treat than mono-species infections. In this in-vitro study, we aimed to determine if a multispecies biofilm, consisting of Gram positive and negative species with different antibiotic susceptibilities could be treated more effectively using high purity antibiotic-loaded calcium sulfate beads (HP-ALCSB) containing vancomycin (VAN) and tobramycin (TOB) in combination than alone. Methods: Three sets of species pairs from bioluminescent strains of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) and clinical isolates, Enterococcus faecalis (EF) and Enterobacter cloacae were screened for compatibility. PA + EF developed intermixed biofilms with similar cell concentrations and so were grown on 316L stainless steel coupons for 72 h or as 24 h agar lawn biofilms and then treated with HP-ALCSBs with single or combination antibiotics and assessed by viable count or bioluminescence and light imaging to distinguish each species. Replica plating was used to assess viability. Results: The VAN + TOB bead significantly reduced the PA + EF biofilm CFU and reduced the concentration of surviving antibiotic tolerant variants by 50% compared to single antibiotics. Conclusions: The combination of Gram-negative and positive targeted antibiotics released from HP-ALCSBs may be more effective in treating multispecies biofilms than monotherapy alone.

Infection is a common cause of impaired fracture healing. In the clinical setting, definitive fracture treatment and infection are often treated separately and sequentially, by different clinical specialties. The ability to treat infection while promoting fracture healing will greatly reduce the cost, number of procedures, and patient morbidity associated with infected fractures. In order to develop new therapies, scientists and engineers must understand the clinical need, current standards of care, pathologic effects of infection on fractures, available preclinical models, and novel technologies. One of the main causes of poor fracture healing is infection; unfortunately, bone regeneration and infection research are typically approached independently and viewed as two separate disciplines. Here, we aim to bring these two groups together in an educational workshop to promote research into the basic and translational science that will address the clinical challenge of delayed fracture healing due to infection. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patie[Q2]nt well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly l[Q3]ower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patient well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly lower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. [ABSTRACT FROM AUTHOR]

C‐C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant‐associated infections (OIAI), but whether CCR2‐mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic‐grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2‐deficient mice. In vivo bioluminescent signals significantly increased in CCR2‐deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony‐forming unit enumeration. S. aureus γ‐hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ‐hemolysin‐deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ‐hemolysin virulence. Although CCR2‐deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2‐deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread. [ABSTRACT FROM AUTHOR]

Abstract Background Staphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains. Methods A total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients’ inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates. Results Biofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses. Conclusion Some genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance.

Objective. To evaluate the resistance rate and production of carbapenemases in Klebsiella pneumoniae with phenotypic resistance to carbapenems isolated from patients with orthopedic infection. Materials and Methods. The materials for the study were tissue samples, aspirates and removed orthopedic devices of patients with orthopedic infection at the Vreden Russian Research Institute of Traumatology and Orthopedics, between 2017 and 2019. K. pneumoniae strains were identified in Microlatest by iEMS ReaderMF. These strains were tested for susceptibility to 15 antimicrobial agents by disk diffusion methods, as described by the EUCAST. The carbapenemase genes were investigated by RT-PCR. Results. Of 858 isolated cultures, 6.8% were resistant to carbapenems. Molecular genetic analysis showed that 43.1% of the cultures had blaNDM gene and 24.1% blaOXA-48. All isolates of K. pneumoniae were characterized by resistance to cefotaxime, moxifloxacin and ciprofloxacin. OXA-48-strains were MDR in 50.0% of cases, XDR in 42.9%, PDR in 7.1%. Strains with NDM-carbapenemases were XDR in 68.0% and PDR in 32.0% of cases. The most effective antibiotic was fosfomycin. Thus, 66.7% of NDM-isolates demonstrated sensitivity to fosfomycin. One isolate was PDR with both NDM and OXA-48. Conclusions. Over the period of three years, carbapenemase-producing K. pneumoniae were isolated in the orthopedic hospital. These isolates were not only resistant to carbapenems, but also to a number of other antimicrobial agents. Isolates differed in resistance phenotypes depending on the presence of carbapenemases group, while strains with gene blaNDM were more resistant than those with blaOXA-48.

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture‐based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigen‐specific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti‐S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture‐related infection (FRI). Anti‐S. aureus and anti‐GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species‐specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture. [ABSTRACT FROM AUTHOR]

Human scabies is a contagious skin condition caused by the Sarcoptes scabiei mite, leading to skin damage and subsequent mechanical irritation from scratching. This impaired skin integrity predisposes individuals to skin infections. While the association between scabies and skin infections caused by Staphylococcus aureus and Streptococcus pyogenes is well-documented, there is limited literature on the risk of surgical site infections in such cases. This case report aims to explore this risk by presenting a case of surgical site infection caused by Streptococcus pyogenes following surgery for a complex elbow injury in a patient with scabies infestation. Scabies infestation leads to direct spread of bacteria and contributes to bacterial infection. Furthermore, complement inhibition and dysbiosis induced by the scabies may facilitate the occurrence of these bacterial infections. Skin infections are frequently encountered in scabies infestations. Preferred incision should be evaluated meticulously before surgery. Further studies are needed to reach a definitive conclusion on this subject. • Human scabies, is a contagious skin condition prevalent in regions with low socioeconomic status and crowded living conditions. • Infections associated with streptococci in implants can lead to significant mortality and morbidity. • Preferred incision should be evaluated meticulously before surgery regarding scabies tunnels. [ABSTRACT FROM AUTHOR]

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains. Methods: A total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients' inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates. Results: Biofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses. Conclusion: Some genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance. [ABSTRACT FROM AUTHOR]

The most common pathologic manifestation of Rhodococcus equi, a gram-positive, facultative intracellular bacterium, is pyogranulomatous pneumonia in foals and weanlings. Hematogenous spread of bacteria may subsequently occur, resulting in joint sepsis, osteomyelitis, or subcutaneous abscessation. Medical records from horses presenting to the Cornell University Equine Hospital from 1998 to 2018 were reviewed for cases diagnosed with R. equi joint and/or bone infection, and information about case progression and outcome were analyzed. We hypothesized that, despite advances in diagnostic imaging, antimicrobials and antimicrobial delivery methods, the prognosis for R. equi joint sepsis and osteomyelitis remains grave for athletic activity and poor for survival. The 12 cases that met the review criteria had a mortality rate of 84% (10/12), with one case lost to follow up after discharge and one case discharged with a grave prognosis for athleticism.

ABSTRACT Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and P. aeruginosa PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of −1.0 V, −1.5 V, or −1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for P. aeruginosa, was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at −1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a >6-log reduction in MRSA and no detectable planktonic P. aeruginosa. All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at −1.0 V and −1.5 V against MRSA. Remarkably, there were no detectable P. aeruginosa CFU following prevention CVCES at −1.0 V or −1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI. IMPORTANCE Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.

Bacterial infection and antibiotic resistance are major threats to human health and very few solutions are available to combat this eventuality. A growing number of studies indicate that cold (non-thermal) plasma treatment can be used to prevent or eliminate infection from bacteria, bacterial biofilms, fungi and viruses. Mechanistically, a cold plasma discharge is composed of high-energy electrons that generate short-lived reactive oxygen and nitrogen species which further react to form more stable compounds (NO2, H2O2, NH2Cl and others) depending on the gas mixture and plasma parameters. Cold plasma devices are being developed for medical applications including infection, cancer, plastic surgery applications and more. Thus, in this review we explore the potential utility of cold plasma as a non-antibiotic approach for treating post-surgical orthopedic infections. [ABSTRACT FROM AUTHOR]

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections.

Background: Bacterial colonization of spinal implants may cause severe complications in patients with early-onset scoliosis. Correct diagnosis and detection of microbiologic formation is crucial to prevent delayed infections caused by bacterial colonization. The purposes of this study were to estimate the rate and risk factors of colonization of vertical expandable prosthetic titanium rib (VEPTR) implants in children and to compare the different methods for detecting microbiologic formation on the spinal implants.Methods: We evaluated prospectively a group of 42 children with spinal deformities with an overall of 95 lengthening surgeries and applied different methods to detect potential bacterial colonization of VEPTR implants: swab of the implant, swab with culture of tissue, analysis of the removed lock, polymerase chain reaction (PCR), and confocal microscopy. Potential risk factors were evaluated.Results: Of 42 patients, 17 (40%) were rated positive for bacterial colonization with Propionibacterium acnes and coagulase-negative staphylococci being the most commonly found bacteria. Risk factors for colonization were increasing age, body height, and weight. The swab with culture of removed tissue yielded most positive results, whereas direct microscopy and PCR were the least sensitive detection methods. Furthermore, commonly used infectious blood parameters were inconclusive.Conclusions: Although the impact of bacterial colonized implants on the health of the patients is not fully elucidated, clinicians aim for prevention of microbiologic formation on implanted devices. Therefore, reliable, inexpensive, and easy to apply diagnostic tools are indispensable to detect colonization. Based on our data, the swab together with tissue culture has the potential to become the method of choice for future diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: A new multiplex real-time polymerase chain reaction (PCR) assay was developed to detect methicillin-resistant Staphylococcus (MRS) and to distinguish between gram-positive and gram-negative bacteria. In this study, we validated the sensitivity and specificity of this assay with periprosthetic joint infections (PJIs) and evaluated the utility of PCR for culture-negative PJI. Methods: Forty-five samples from 23 infectious PJI cases and 106 samples from 64 non-infectious control cases were analyzed by real-time PCR using a LightCycler NanoVR system. Twenty-eight clinical samples, comprising bacteria of known species isolated consecutively in the microbiological laboratory of our hospital, were used to determine the spectrum of bacterial species that could be detected using the new multiplex primers and probes. Results: The sensitivity and specificity of the MRS- and universal-PCR assays were 92% and 99%, and 91% and 88%, respectively. Twenty-eight species of clinically isolated bacteria were detected using this method and the concordance rate for the identification of gram-positive or gram-negative organisms was 96%. Eight samples were identified as PCR-positive despite a culture-negative result. Conclusion: This novel multiplex real-time PCR system has acceptable sensitivity and specificity and several advantages; therefore, it has potential use for the diagnosis of PJIs, particularly in culture-negative cases. [ABSTRACT FROM AUTHOR]

Background: The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction.Methods: A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score.Results: With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%.Conclusions: Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to evaluate the feasibility and clinical efficacy of bridging vein transplantation to deal with the vessel shortage during free vascularized fibular grafting for reconstructing infected bone defects of the femur.Methods: Twelve patients (aged 15-58 years) with infected bone defects of the femur (between 6.0 and 18.0cm) were recruited in this study. Vacuum sealing drainage were applied after extensive debridement of the infected bone defects and irrigated with 0.9% sodium chloride solution for 1-2 weeks. After the drainage was clear and the focal infections were controlled, the free vascularized fibula was harvested for reconstructing the femoral bone defects. The vascularized fibula was grafted and fixated appropriately at the recipient site. The autogenous great saphenous vein was harvested, one end was anastomosed and bridged the vascular pedicles of the fibular grafts, and the other end anastomosed the artery and/or the vein in the recipient healthy site.Results: Mean length of vein transplantation with vascularized fibular graft was 10.2 cm (range 7-15cm). All patients had good radiological healing without recorded nonunion or malunion. No patient developed deep infection or implant failure. Primary bone healing was achieved in 10 patients; however, 2 grafted fibular formed pseudarthrosis with the recipient femoral and then healed after a secondary surgery. One patient suffered from graft stress fracture after bone healing and healed after external fixation. After the mean follow-up of 30 months (9-72 months), according to the Enneking scoring system, clinical outcomes were excellent in 7 patients, good in 4 and fair in one. The functional recovery rate of the lesion limb was 89.4%.Conclusions: Free vascularized fibular graft with vein transplantation bridged vascular pedicle can effectively repair the infected bone, improve blood supply to the bone defect site, and help control infection. It is a feasible and effective treatment for infected bone defects of the femur with poor soft tissue conditions, or blood supply vessel shortage. [ABSTRACT FROM AUTHOR]

Considerable progress has been made toward elucidating the mechanism of Staphylococcus aureus aggregation in synovial fluid. In this study, aggregate morphology was assessed following incubation under several simulated postsurgical joint conditions. Using fluorescently labeled synovial fluid polymers, we show that aggregation occurs through two distinct mechanisms: (i) direct bridging between S. aureus cells and host fibrinogen and (ii) an entropy-driven depletion mechanism facilitated by hyaluronic acid and albumin. By screening surface adhesin-deficient mutants ( clfA , clfB , fnbB , and fnbA ), we identified the primary genetic determinant of aggregation in synovial fluid to be clumping factor A. To characterize this bridging interaction, we employed an atomic force microscopy-based approach to quantify the binding affinity of either wild-type S. aureus or the adhesin mutant to immobilized fibrinogen. Surprisingly, we found there to be cell-to-cell variability in the binding strength of the bacteria for immobilized fibrinogen. Superhigh-resolution microscopy imaging revealed that fibrinogen binding to the cell wall is heterogeneously distributed at both the single cell and population levels. Finally, we assessed the antibiotic tolerance of various aggregate morphologies arising from newly deciphered mechanisms of polymer-mediated synovial fluid-induced aggregation. The formation of macroscopic aggregates under shear was highly tolerant of gentamicin, while smaller aggregates, formed under static conditions, were susceptible. We hypothesize that aggregate formation in the joint cavity, in combination with shear, is mediated by both polymer-mediated aggregation mechanisms, with depletion forces enhancing the stability of essential bridging interactions. IMPORTANCE The formation of a bacterial biofilm in the postsurgical joint environment significantly complicates the resolution of an infection. To form a resilient biofilm, incoming bacteria must first survive the initial invasion of the joint space. We previously found that synovial fluid induces the formation of Staphylococcus aureus aggregates, which may provide rapid protection during the early stages of infection. The state of the host joint environment, including the presence of fluid flow and fluctuating abundance of synovial fluid polymers, determines the rate and size of aggregate formation. By expanding on our knowledge of the mechanism and pathogenic implications of synovial fluid-induced aggregation, we hope to contribute insights for the development of novel methods of prevention and therapeutic intervention.

Objectives: Outpatient parenteral antimicrobial therapy (OPAT) is an effective way of treating infections, but complications are common. We identified patient characteristics and OPAT treatment factors associated with increased risk of OPAT-related complications.Methods: We used a retrospective cohort design that assessed 337 adult patients treated with OPAT for orthopedic and neurosurgical infections between August 1, 2008 and May 30, 2010. Independent variables included demographics, infection characteristics, lead time factors, OPAT treatment factors, and comorbid conditions. Multivariable log-binomial regression was used to estimate the risk of OPAT complications.Results: The mean patient age was 55 years (range 19-87), 86% had an orthopedic infection, and 44% were treated with intravenous vancomycin. OPAT complications were seen in 45% (152/337) of the cohort. Risk ratios for OPAT complications were 1.9 (95% confidence interval 1.4-2.5) in patients having no primary care provider, 1.7 (95% confidence interval 1.3-2.1) for those treated with vancomycin.Conclusions: Identifying specific patient characteristics and OPAT treatment factors could facilitate OPAT process improvements to reduce the risk of OPAT complications for vulnerable patients. [ABSTRACT FROM AUTHOR]

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Abstract: The Del Pozo and Patel (DPP) algorithm permits to identify suitable candidates for debridement and implant retention (DR) in prosthetic joint infections (PJI), but does not include gram-negative bacilli (GNB) as a risk factor of worst outcome. We conducted a retrospective study to validate the DPP algorithm and propose a simplified algorithm including GNB PJI. From 2002 to 2009, 73 PJI underwent surgery; 55% were chosen according to PDD algorithm. Non-adherence increased the risk of treatment failure (HR = 4.2). Performing DR in the presence of GNB PJI and performing DR in a joint prosthesis implanted for >3 months without hematogenous infection were independent risk factors. Our simplified algorithm, based on these 2 criteria, showed comparable performance to the DPP algorithm but increased eligibility for DR by a 2.4 fold. [Copyright &y& Elsevier]