Search Results (124)

Background/Objectives: Jaw osteomyelitis (OM) is a refractory purulent inflammation caused by bacterial infection, characterized by persistent infection, excessive bone resorption, and resultant bone defects. Currently, mainstream therapies for jaw OM struggle to eradicate persistent infections, avoid antibiotic resistance, and repair infected bone defects, posing a critical challenge in clinical practice. Methods: Herein, the Fe₃O₄@ZIF-8 core–shell nanoparticles (NPs) platform designed for jaw OM treatment consisted of Fe₃O₄ as the core and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Results: The core–shell platform not only integrated the pH-responsive degradation capability of ZIF-8 but also retained the superparamagnetism of Fe₃O₄ NPs. In the acidic, infectious microenvironment, Fe₃O₄@ZIF-8 NPs underwent continuous degradation, releasing Zn²⁺, thereby conferring potent antibacterial activity. The specific antibacterial mechanism of the nanoparticles lies in the fact that high concentrations of Zn²⁺ directly disrupted bacterial cell membranes and inhibited the bacterial heat shock response. This dysregulates bacterial proteostasis, rendering the bacteria more sensitive to external adverse stresses, ultimately leading to bacterial death. With ZIF-8 framework degradation, the encapsulated Fe₃O₄ NPs were released. Under static magnetic field (SMF) synergy, Fe₃O₄ NPs collaborated with Zn²⁺ to promote bone regeneration and repair infected bone defects in jaw OM lesions. Conclusions: As a multifunctional core–shell platform, Fe₃O₄@ZIF-8 NPs meet the dual clinical needs of antibiosis and osteogenesis, offering a promising translational strategy for jaw OM therapy. Full article

Osteoimmunology examines the bidirectional interactions between the skeletal and immune systems, focusing on the mechanisms by which immune cells regulate bone homeostasis and how the bone microenvironment modulates immune responses. Chronic inflammation is a major driver of bone loss, and infections of bacterial or viral origin perturb bone remodeling with consequences for host defense. In infected bone tissue, immune cell infiltration and the release of cytokines and soluble mediators alter the activity of osteoclasts and osteoblasts, thereby promoting bone erosion and structural remodeling. Recent studies highlight how immune dysregulation contributes to the pathogenesis of osteomyelitis and other infection-associated bone disorders, implicating specific inflammatory pathways and cellular interactions as potential therapeutic targets. This review synthesizes current evidence on direct and indirect mechanisms by which infection affects bone, identifies gaps in mechanistic understanding, and discusses implications for diagnosis and intervention. Full article

Background: Diabetic foot osteomyelitis (DFO) is a severe complication requiring effective empiric antibiotic therapy to prevent amputation. While global guidelines suggest tailoring therapy based on climate zones, limited data exist regarding seasonal variations within a single region experiencing distinct seasonal extremes. This study investigated whether the bacterial etiology of DFO differs significantly between the hot, humid summer and the cold, dry winter in the Republic of Korea. Methods: We conducted a retrospective cohort study of 85 patients with DFO who underwent lower extremity amputation between January 2018 and October 2024. Patients were categorized into Summer (July–August) and Winter (December–January) groups. Deep tissue or bone specimens were analyzed to compare pathogen prevalence. Results: A total of 85 patients were included (Summer: n = 45; Winter: n = 40). While Staphylococcus species were the most common pathogens overall (30.6%), a seasonal shift was observed. The proportion of Gram-negative isolates was higher in Summer (50.7%) compared to Winter (35.1%), representing a notable clinical trend (p = 0.080). Specifically, Pseudomonas aeruginosa and Escherichia coli were more frequently isolated during the summer months. Furthermore, polymicrobial infections were more prevalent in Summer (62.2%) compared to Winter (45.0%), although this did not reach statistical significance (p = 0.111). Conclusions: The microbiological profile of DFO exhibits seasonal variations. The observed trend toward an increased prevalence of Gram-negative and polymicrobial infections during the Korean summer suggests that empiric antibiotic guidelines should be dynamic rather than static. Full article

Background: Bone and joint infections (BJIs), including osteomyelitis, septic arthritis, and periprosthetic joint infections, typically require prolonged antimicrobial therapy and often involve complex outpatient management. Oritavancin, a long-acting lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria, has emerged as a potential off-label option for BJIs owing to its favourable pharmacokinetic and pharmacodynamic properties. Objectives: To provide a comprehensive overview of the pharmacological rationale, microbiological activity, and available clinical evidence supporting the use of oritavancin in BJIs. Methods: A comprehensive narrative review of the literature was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), focusing on publications from 2011 to 2025. Observational studies, case series, and case reports describing the off-label use of oritavancin in BJIs were considered. Results: The available literature primarily consists of observational studies and real-world experiences. Eighteen studies met the inclusion criteria. Oritavancin was most frequently evaluated for osteomyelitis (n = 14 studies), prosthetic joint infections (n = 10) and septic arthritis (n = 5). Multi-dose regimens, typically including a 1200 mg loading dose followed by weekly doses of 800–1200 mg, were the most commonly described strategies. Reported clinical success rates generally ranged from approximately 70% to over 90%. Oritavancin was overall well tolerated, with adverse events being mostly mild and self-limiting. Conclusions: Current evidence suggests that oritavancin may represent an effective and well-tolerated off-label option for selected patients with Gram-positive BJIs. Its use may offer practical advantages, including reduced hospitalization and avoidance of prolonged intravenous antimicrobial therapy, particularly in patients for whom standard treatment approaches are challenging. Full article

Bone and joint infections (BJI) remain among the most challenging conditions in orthopaedics due to their complex pathophysiology, frequent association with biofilm formation on bone and implant surfaces, and the rising prevalence of antibiotic-resistant pathogens. Conventional antibiotic therapies, although central to current clinical practice, are often limited by poor biofilm penetration, disruption of the host microbiota, and the increasing emergence of multidrug resistance, particularly in chronic infections such as osteomyelitis and prosthetic joint infections. This review provides a comprehensive exploration of bacteriophage therapy as a targeted, non-antibiotic strategy for the management of BJIs. Bacteriophages exhibit unique biological characteristics, including strict host specificity, self-amplifying antibacterial activity, and the capacity to disrupt biofilms through bacterial lysis and phage-derived enzymes. Evidence from in vitro investigations, animal models, and emerging clinical studies demonstrates the promising efficacy of phages and phage lysins against key BJI pathogens, particularly Staphylococcus aureus, with favourable safety profiles and encouraging rates of infection control, especially when used as adjuncts to surgery and antibiotics. Despite this potential, challenges such as narrow host range, variable pharmacokinetics, immunogenicity, and underdeveloped regulatory frameworks continue to limit widespread clinical adoption. Addressing these barriers through standardized phage selection, improved delivery strategies, combination therapies, and coordinated regulatory efforts will be critical to realizing the full therapeutic potential of phage-based interventions for antibiotic-resistant bone and joint infections. Full article

Bone infections, including osteomyelitis, prosthetic joint infections, and fracture-related infections, represent a persistent and growing clinical problem associated with substantial morbidity, mortality, and healthcare costs. Their management is complicated by limited bone vascularization, biofilm formation, intracellular bacterial persistence, dysregulated host immune responses and reduced antibiotic delivery to the infection site, which promote chronic infection and recurrence. The limitations of conventional treatment strategies based on surgical debridement and prolonged systemic antibiotic therapy, together with their association with antimicrobial resistance and systemic toxicity, have led to growing interest in alternative and adjunctive therapeutic approaches. Local antibiotic delivery systems, such as polymethyl methacrylate, calcium sulfate, hydroxyapatite-based composites, hydrogels, antibiotic-impregnated bone grafts, and nanoparticle carriers, enable high local antimicrobial concentrations while minimizing systemic exposure. From a different therapeutic perspective, immunomodulatory strategies, including mesenchymal stem cell-based therapies, cytokine-targeted interventions, bacteriophages, quorum-sensing inhibitors, and non-antibiotic antimicrobials, represent emerging approaches aimed at improving infection control and supporting bone regeneration. Advances in biomarker profiling, molecular diagnostics, and artificial intelligence-assisted analyses further support personalized approaches to diagnosis, monitoring, and treatment. Despite encouraging early results, clinical translation remains limited by methodological and regulatory challenges, underscoring the need for integrated, innovative treatment strategies. Full article

Background and Clinical Significance: Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that primarily affects children and adolescents, with females more frequently impacted. The condition remains poorly understood, though cytokine dysregulation and inflammasome activation are believed to contribute to its pathogenesis. Clinically, CNO is often difficult to distinguish from infectious osteomyelitis, as presenting symptoms such as bone pain, swelling, and functional limitation are nonspecific, while cultures are frequently negative. As a diagnosis of exclusion, delays in recognition can lead to prolonged or unnecessary antibiotic exposure and uncertainty in management. Case Presentation: A 14-year-old male with a history of left second toe osteomyelitis initially diagnosed in 2021. Despite negative cultures and limited histopathologic findings, he received multiple antibiotic courses with little improvement, and the digit remained chronically swollen. Three years later, a repeat evaluation revealed osseous resorption of the middle and distal phalanges, and a biopsy confirmed acute and mild chronic fibrosing osteomyelitis, consistent with CNO. Given the risk of progression and possible amputation, surgical reconstruction was pursued. The patient underwent autologous calcaneal bone grafting with digital fusion using a K-wire. At three months and one year postoperatively, radiographs demonstrated solid fusion of the digit with maintained activity and resolution of pain. Conclusions: This case emphasizes the diagnostic complexity of CNO and the importance of considering it in children with culture-negative or recurrent osteomyelitis. It further illustrates how timely surgical intervention can preserve function and quality of life while avoiding unnecessary amputation. Full article

Staphylococcus species are saprophytic, opportunistic, and nosocomial pathogens that frequently co-infect with other microorganisms, causing severe infections in birds. Some of the notable examples include bacterial chondronecrosis with osteomyelitis (BCO), cellulitis, dermatitis, and systemic infections. Understanding of how Staphylococcus spp. cause infections evading the host immune system is crucial for helping farmers and veterinarians develop long-term solutions for poultry production system management. The aim of this review is to broaden the understanding of Staphylococcus spp. epidemiology, virulence, genomic adaptability and coinfection patterns. The peer-reviewed articles were obtained from various databases, including Google Scholar, Web of Science, and PubMed. The review primarily focused on papers published between 1999 and 2025. The review presents an opportunity to identify research gaps and apply this knowledge to develop innovative approaches to address staphylococcal infections in broiler chickens. Additionally, BCO is often attributed to coinfection with Staphylococcus species and other pathogens. Full article

Bacterial chondronecrosis with osteomyelitis (BCO), and its associated lameness, is one of the most common and devastating issues the poultry industry constantly faces, both globally and domestically. Leveraging the currently accepted “leaky gut” model of pathogenesis, this study aims to evaluate the cecal community of broilers reared under the aerosol transmission BCO induction model. A trial involving 1320 Cobb 500 broilers was conducted using the same induction model for 56 d with the following treatments: (1) positive control (PC)—untreated birds on wire-flooring pens; (2) negative control (NC)—untreated birds on litter-flooring pens; (3) LOW—birds treated with probiotic Enterococcus faecium spray on day-of-hatch (2.0 × 10⁹ CFU/bird); and (4) HIGH—birds treated with LOW spray combined with probiotic Bacillus amyloliquefaciens/Bacillus subtilis inclusion in the diet (492.1 mg/kg). Cecal contents were collected from six birds per treatment on d14, d28, d42, and d56 of the experiment; then, DNA was extracted and sent for 16 s V3–V4 amplicon sequencing. Returned sequences were assembled and taxonomically assigned, after which diversity indices were analyzed (including alpha, beta, and abundance). No significant effect was found between all treatments and positive/negative control groups in all timepoints, but timepoints were significantly different from each other in both alpha and beta diversity indices (p < 0.05). Abundance analysis also showed a high Bacillota:Bacteroidota ratio (average 18.87; p < 0.0001) with Bacillota (Firmicutes) dominating at 95.57% on average across all treatments, followed by Bacteroidota at 5.06% and Pseudomonadota at 2.59%. These findings characterize in detail the cecal microbiome in populations of broilers reared under the novel aerosol transmission induction model, offering further insights and possibilities into studies of BCO etiology and pathology. Full article

Bacterial Chondronecrosis with Osteomyelitis (BCO) lameness is an infection of opportunistic bacteria in the structural skeletal bones impacting multiple animal species, particularly poultry species. BCO lameness results in significant financial losses to industrial poultry production and increases the risk of foodborne illnesses, posing a major threat to consumers’ food safety. As BCO lameness is an inherent risk of fast body weight gain in poultry species, especially broiler chickens, abundant studies have been conducted in broilers and turkeys. Nevertheless, BCO lameness incidence in ducks remains elusive. Thus, this is the first survey investigating the prevalence of BCO lameness cases in ducks. The survey was conducted in commercial duck farms in Indonesia, the fourth biggest duck-producing country globally. Two hundred birds from four commercial duck farms in Mojokerto, East Java, Indonesia, were necropsied to examine their lameness lesions in the femoral head and proximal tibia. Of the 44% birds showing BCO lameness lesions, 3% were evidently clinically lame birds, particularly exhibiting limping gait. Femoral head separation (FHS) and tibial head necrosis (THN) are the most frequently observed lesions in ducks, representing a mild-to-moderate BCO lameness state. Based on the results of this study, intervention measures to boost the immune system and skeletal bone integrity of ducks are urgently required. Full article

Diabetic foot infections (DFIs) are a significant complication in patients with diabetes, often leading to severe clinical complications including amputation and increased mortality rates. The effective management of these infections is complicated by the rise in antibiotic resistance among the microbial populations involved. In this paper, we undertake a systematic review and meta-analysis to explore the bacterial profiles, as well as their antibiotic resistance patterns in DFIs, encompassing studies published between 2014 and 2024. A total of 28 studies were selected from several databases, including PubMed, Google Scholar, EBSCOhost, and ScienceDirect, published from 2014 to 2024, specifically focusing on diabetic foot infections and antibiotic resistance. Diabetic foot infections arise from a combination of factors, including peripheral neuropathy, poor circulation, and immune system impairment, making diabetic patients prone to unnoticed injuries, impaired wound healing, and a higher risk of infections. The severity of DFIs often depends on the size and depth of the ulcers, with larger, deeper ulcers posing additional risks of infection and complications, such as osteomyelitis and sepsis. Our study synthesizes information on the total isolates of microbes, their resistance to one or more groups of antibiotics, and resistance panel results across multiple antibiotics, including amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, ciprofloxacin, and others. We meticulously catalog the resistance of key bacterial strains—Escherichia coli, Enterobacter spp., Proteus spp., Pseudomonas spp., Staphylococcus aureus, and others—highlighting patterns of resistance to single and multiple antibiotic groups. This systematic review also analyzes the correlations of various comorbidities reported by the diabetic foot infection patient populations in the included studies with multiple antibiotic resistance patterns. Subsequently, this analytical review study addresses the rising prevalence of antibiotic-resistant pathogens and underscores the need for antibiotic stewardship programs to promote judicious use of antibiotics, reduce the spread of resistant strains, and enhance therapeutic outcomes. In addition, the review discusses the implications of resistance to empirical antibiotic treatments, underscoring the necessity for tailored antibiotic therapy based on culture and sensitivity results to optimize treatment outcomes. Full article

Background: Bacterial Chondronecrosis with Osteomyelitis (BCO) is a significant issue affecting the welfare and economy of the broiler industry, causing substantial revenue losses annually. This disease is frequently associated with Staphylococcus spp. and Enterococcus spp. infections and necrosis of leg and vertebral bones. The typical annual lameness incidence of approximately 3–5% may increase to 30% during outbreaks. Neither the etiology or pathogenesis of the disease has been comprehended, nor have effective preventative measures been identified. Electron beam (eBeam) technology is renowned for producing efficient whole-cell vaccines by preventing bacterial multiplication through irreversible DNA shredding while preserving the integrity of membrane proteins (immunogenic epitopes). This study aims to reduce BCO-induced lameness in broiler chickens via in ovo immunization using eBeam-inactivated multi-strain Staphylococcus. Methods: A total 1080 birds were assigned to four vaccination groups: eBeam-inactivated, formalin-inactivated, combination of eBeam- and formalin-inactivated, and sham (vehicle). The birds were directly exposed to aerosolized, natural BCO challenge until 56 days of age. Results: Birds vaccinated with the eBeam-inactivated Staphylococcus vaccine showed a significant reduction (>50%) in daily cumulative lameness compared to other groups and a decrease in Staphylococcus colonization was observed in the leg joints of treated birds. Conclusions: the eBeam-inactivated Staphylococcus vaccine successfully prevented BCO lameness in broiler chickens. Full article

Staphylococcus aureus is the most common pathogen causing osteomyelitis, a hardly recoverable bone infection that generates significant burden to patients. Osteomyelitis mouse models have long and successfully served to provide phenomenological insights into both pathogenesis and host response. However, direct in situ monitoring of bone microbial pathogenesis and immune response at the cellular level is still conspicuously missing in the published literature. Here, we update a standard pyogenic osteomyelitis in Wistar rat model, in order to investigate bacterial localization and immune response in osteomyelitis of rat tibia upon adding in situ analyses by spectrally resolved Raman spectroscopy. Raman experiments were performed one and five weeks post infections upon increasing the initial dose of bacterial inoculation in rat tibia. Label-free in situ Raman spectroscopy clearly revealed the presence of Staphylococcus aureus through exploiting peculiar signals from characteristic carotenoid staphyloxanthin molecules. Data were collected as a function of both initial bacteria inoculation dose and location along the tibia. Such strong Raman signals, which relate to single and double bonds in the carbon chain backbone of carotenoids, served as efficient bacterial markers even at low levels of infection. We could also detect strong Raman signals from cytochrome c (and its oxidized form) from bone cells in response to infection and inflammatory paths. Although initial inoculation was restricted to a single location close to the medial condyle, bacteria spread along the entire bone down to the medial malleolus, independent of initial infection dose. Raman spectroscopic characterizations comprehensively and quantitatively revealed the metabolic state of bacteria through specific spectroscopic biomarkers linked to the length of staphyloxanthin carbon chain backbone. Moreover, the physiological response of eukaryotic cells could be quantified through monitoring the level of oxidation of mitochondrial cytochrome c, which featured the relative intensity of the 1644 cm⁻¹ signal peculiar to the oxidized molecules with respect to its pyrrole ring-breathing signal at 750 cm⁻¹, according to the previously published literature. In conclusion, we present here a novel Raman spectroscopic approach indexing bacterial concentration and immune response in bone tissue. This new approach enables locating and characterizing in situ bone infections, inflammatory host tissue reactions, and bacterial resistance/adaptation. Full article

Background: Helcococcus kunzii, a facultative anaerobe and Gram-positive coccus, has been documented as a cunning pathogen, mainly in immunocompromised individuals, as evidenced by recent clinical and microbiological reports. It has been associated with a variety of polymicrobial infections, comprising diabetic foot ulcers, prosthetic joint infections, osteomyelitis, endocarditis, and bloodstream infections. Despite its emerging clinical relevance, no licensed vaccine or targeted immunotherapy currently exists for H. kunzii, and its rising resistance to conventional antibiotics presents a growing public health concern. Objectives: In this study, we employed an integrated subtractive proteomics and immunoinformatics pipeline to design a multi-epitope subunit vaccine (MEV) candidate against H. kunzii. Initially, pan-proteome analysis identified non-redundant, essential, non-homologous, and virulent proteins suitable for therapeutic targeting. Methods/Results: From these, two highly conserved and surface-accessible proteins, cell division protein FtsZ and peptidoglycan glycosyltransferase FtsW, were selected as promising vaccine targets. Comprehensive epitope prediction identified nine cytotoxic T-lymphocyte (CTL), five helper T-lymphocyte (HTL), and two linear B-cell (LBL) epitopes, which were rationally assembled into a 397-amino-acid-long chimeric construct. The construct was designed using appropriate linkers and adjuvanted with the cholera toxin B (CTB) subunit (NCBI accession: AND74811.1) to enhance immunogenicity. Molecular docking and dynamics simulations revealed persistent and high-affinity ties amongst the MEV and essential immune receptors, indicating a durable ability to elicit an immune reaction. In silico immune dynamic simulations predicted vigorous B- and T-cell-mediated immune responses. Codon optimization and computer-aided cloning into the E. coli K12 host employing the pET-28a(+) vector suggested high translational efficiency and suitability for bacterial expression. Conclusions: Overall, this computationally designed MEV demonstrates favorable immunological and physicochemical properties, and presents a durable candidate for subsequent in vitro and in vivo validation against H. kunzii-associated infections. Full article

Biofilms are structured communities of microorganisms encased in a self-produced extracellular matrix, and they represent one of the most widespread forms of microbial life on Earth. Their presence poses serious challenges in both environmental and clinical settings. In natural and industrial systems, biofilms contribute to water contamination, pipeline corrosion, and biofouling. Clinically, biofilm-associated infections are responsible for approximately 80% of all microbial infections, including endocarditis, osteomyelitis, cystic fibrosis, and chronic sinusitis. A particularly critical concern is their colonization of medical devices, where biofilms can lead to chronic infections, implant failure, and increased mortality. Implantable devices, such as orthopedic implants, cardiac pacemakers, cochlear implants, urinary catheters, and hernia meshes, are highly susceptible to microbial attachment and biofilm development. These infections are often recalcitrant to conventional antibiotics and frequently necessitate surgical revision. In the United States, over 500,000 biofilm-related implant infections occur annually, with prosthetic joint infections alone projected to incur revision surgery costs exceeding USD 500 million per year—a figure expected to rise to USD 1.62 billion by 2030. To address these challenges, surface modification of medical devices has emerged as a promising strategy to prevent bacterial adhesion and biofilm formation. This review focuses on recent advances in chemical surface functionalization using non-antibiotic agents, such as enzymes, chelating agents, quorum sensing quenching factors, biosurfactants, oxidizing compounds and nanoparticles, designed to enhance antifouling and mature biofilm eradication properties. These approaches aim not only to prevent device-associated infections but also to reduce dependence on antibiotics and mitigate the development of antimicrobial resistance. Full article