The diabetic sausage toe: Prevalence, presentation and outcomes.

Osteomyelitis (OM) in diabetic foot infection could have many presentations such as an infected ulcer spreading to the bone or superimposed to Charcot neuroarthropathy. However, the sausage toe as a diabetic OM presentation was very rarely investigated; therefore, this study aims to assess the prevalence and signs of this presentation along with treatment modalities and outcomes. This is a retrospective series of patients presenting a sausage toe on admission. Several methods were conducted to diagnose OM, and three treatment modalities were applied. Two groups were compared: acute and chronic sausage toes. Outcomes were defined as sausage toe prevalence, ulcer location, OM prevalence, and comparative treatment results. Out of 82 diabetic toe infection cases, 24 (30%) presented as 'sausage toe'. The side of the proximal interphalangeal joint of the lateral toes was the most frequent ulcer location (50%), mostly on the dorsal aspect followed by the side aspect. There were 15 (62.5%) acute cases and 9 (37.5%) chronic cases. MRI showed signs of OM in 21 (87.5%) cases and signs of septic arthritis in 3 (12.5%) cases. At the final follow-up, a successful treatment was recorded in five (20%) cases with antibiotics alone. Out of the 19 (42%) procedures, conservative surgery was performed successfully in 8 (58%) cases while amputation was needed in 11 (45.8%) cases. There was no significant difference in amputation frequency between acute and chronic groups. This is the first study documenting the sausage toe as a prevalent presentation of diabetic toe infection. The deformity is conclusive of deep infection with a very high osteomyelitis frequency. Surgery is often required for infection control and healing, mainly for chronic cases, and treatment outcomes did not differ between acute and chronic sausage toe groups. It could be beneficial to include this entity in the diabetic wound classification systems.

Bone and joint infections due to melioidosis; diagnostic and management strategies to optimise outcomes.

BACKGROUND: Melioidosis, a life-threatening infection caused by the gram negative bacterium Burkholderia pseudomallei, can involve almost any organ. Bone and joint infections (BJI) are a recognised, but incompletely defined, manifestation of melioidosis that are associated with significant morbidity and mortality in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We identified all individuals with BJI due to B. pseudomallei managed at Cairns Hospital in tropical Australia between January 1998 and June 2023. The patients' demographics, their clinical findings and their treatment were correlated with their subsequent course. Of 477 culture-confirmed cases of melioidosis managed at the hospital during the study period, 39 (8%) had confirmed BJI; predisposing risk factors for melioidosis were present in 37/39 (95%). However, in multivariable analysis only diabetes mellitus was independently associated with the presence of BJI (odds ratio (95% confidence interval): 4.04 (1.81-9.00), p = 0.001). BJI was frequently only one component of multi-organ involvement: 29/39 (74%) had infection involving other organs and bacteraemia was present in 31/39 (79%). Of the 39 individuals with BJI, 14 (36%) had osteomyelitis, 8 (20%) had septic arthritis and 17 (44%) had both osteomyelitis and septic arthritis; in 32/39 (83%) the lower limb was involved. Surgery was performed in 30/39 (77%). Readmission after the initial hospitalisation was necessary in 11/39 (28%), 5/39 (13%) had disease recrudescence and 3/39 (8%) had relapse; 4/39 (10%) developed pathological fractures. ICU admission was necessary in 11/39 (28%) but all 11 of these patients survived. Only 1/39 (3%) died, 138 days after admission, due to his significant underlying comorbidity. CONCLUSIONS: The case-fatality rate from melioidosis BJI in Australia's well-resourced health system is very low. However, recrudescence, relapse and orthopaedic complications are relatively common and emphasise the importance of collaborative multidisciplinary care that includes early surgical review, aggressive source control, prolonged antibiotic therapy, and thorough, extended follow-up.

Infectious Aspects of Chronic Wounds.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware.

The utility of negative pressure wound therapy in the management of complex deep cardiothoracic surgical site infections.

BACKGROUND: Complex deep surgical site infection in the cardiothoracic surgery patient that reaches the sternum and even the mediastinum, causing osteomyelitis and mediastinitis, is associated with high rates of morbidity and mortality. Negative pressure wound therapy (NPWT) can aid in achieving favorable outcomes in patients with complex surgical site infections by promoting wound healing and shortening the hospital stay. NPWT is widely recognized for its advantages and has recently been used in both cardiothoracic and non-cardiothoracic settings. OBJECTIVE: To evaluate the efficacy of NPWT in the management of complex deep surgical site infection after cardiothoracic surgery. MATERIALS AND METHODS: A retrospective chart review of all complex cardiothoracic cases admitted to the cardiac and thoracic surgery divisions for surgical intervention to treat postoperative surgical wound infections. RESULTS: A total of 18 patients were included, with a male-to-female ratio of 5:4. The mean (SD) age was 48.7 (16.5) years. The cases reviewed were complex, and the duration of the NPWT application ranged from 4 days to 120 days, with an average hospital stay of 62.8 days. Seventy-eight percent of patients required antibiotics (or had positive wound cultures); in 55.6% of these patients, polymicrobial infection was detected. No major complications were related to NPWT. CONCLUSION: The study findings show that using NPWT in complex deep sternal and thoracic infections can enhance wound healing, shorten the hospital stay, and decrease morbidity and mortality secondary to wound infection in cardiothoracic patients.

Role of bone single photon emission computed tomography/computed tomography in managing chronic fracture-related infections: Determining the depth of infection and avoiding unnecessary bone procedures.

PURPOSE: Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures; they remain a significant clinical challenge. Here, we aimed to investigate the viability of focusing on soft-tissue management in patients suspected of chronic FRI, who exhibit no significant bony uptake on bone single photon emission computed tomography (SPECT)/computed tomography (CT) scans. METHODS: Between January 2016 and January 2022, we managed 25 patients with chronic FRI or post-traumatic osteomyelitis using technetium 99m-methyl diphosphonate bone SPECT/CT to assess infection depth. Among them, 13 patients showing negligible bony uptake were included and categorized into two groups based on wound discharge reaching the bone/implant (Criteria 1, n = 6) or not (Criteria 2, n = 7). RESULTS: Patients in the Criteria 1 group were treated with antibiotics and soft tissue debridement without bony procedure. The average duration of antibiotic therapy was 6.7 weeks. Treatments were individualized, including implant changes, local flaps, skin grafts, and negative pressure wound therapy. No recurrence was reported in the mean follow-up of 21.3 months. Patients in the Criteria 2 group were treated with oral antibiotics (mean duration: 5.9 weeks) and daily wound dressings. No recurrence was reported in the mean follow-up of 26.0 months, and no surgical interventions were required. CONCLUSION: This study demonstrates the feasibility of focusing on soft-tissue management in patients with chronic FRI showing minimal bony uptake on bone SPECT/CT. Our treatment protocol avoided unnecessary surgical bone procedures, resulting in successful clinical outcomes with no recurrences.

Clinical characteristics and outcomes associated with culture-negative status in limb osteomyelitis patients.

Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

Activated allograft combined with induced menbrane technique for the reconstruction of infected segmental bone defects.

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4-17) cm in length. After a mean follow-up of 71.84 (61-82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5-28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Clinical and ultrasound features of 46 children with suppurative osteoarthritis: experience from two centers.

OBJECTIVE: Diagnosing musculoskeletal infections in children is challenging. In recent years, with the advancement of ultrasound technology, high-resolution ultrasound has unique advantages for musculoskeletal children. The aim of this work is to summarize the ultrasonographic and clinical characteristics of children with pyogenic arthritis and osteomyelitis. This study provides a simpler and more effective diagnostic basis for clinical treatment. METHODS: Fifty children with osteomyelitis or arthritis were diagnosed via ultrasound, and the results of the ultrasound diagnosis were compared with those of magnetic resonance imaging and surgery. Clinical and ultrasound characteristics were also analyzed. RESULTS: Out of 50 patients, 46 were confirmed to have suppurative infection by surgical and microbiological examination. Among these 46 patients, 26 were diagnosed with osteomyelitis and 20 had arthritis. The manifestations of osteomyelitis were subperiosteal abscess (15 patients), bone destruction (17 patients), bone marrow abscess (9 patients), and adjacent joint abscess (13 patients). Osteomyelitis mostly affects the long bones of the limbs, femur and humerus (10 and 9 patients, respectively), followed by the ulna, radius, tibia and fibula (one patient each). The manifestations of arthritis were joint pus (20 patients) and joint capsule thickening (20 patients), and hip dislocation (8 patients). All the patients had arthritis involving the hip joint. CONCLUSION: Subperiosteal abscess, bone destruction, and joint abscess with dislocation are ultrasonographic features of pyogenic osteoarthritis. The findings of this work can improve the early diagnosis and differentiation of pyogenic osteoarthritis and provide a reliable basis for treatment.

Diabetic Foot Infections in the Emergency Department.

Diabetic foot infection (DFI) is among the most common diabetic complications requiring hospitalization. Prompt emergency department diagnosis and evidence-based management can prevent eventual amputation and associated disability and mortality. Underlying neuropathy, arterial occlusion, immune dysfunction, and hyperglycemia-associated dehydration and ketoacidosis can all contribute to severity and conspire to make DFI diagnosis and management difficult. Serious complications include osteomyelitis, necrotizing infection, and sepsis. Practice guidelines are designed to assist frontline providers with correct diagnosis, categorization, and treatment decisions. Management generally includes a careful lower extremity examination and plain x-ray, obtaining appropriate tissue cultures, and evidence-based antibiotic selection tailored to severity.

Chronic Nonspinal Osteomyelitis in Adults: Consensus Recommendations on Percutaneous Bone Biopsies from the Society of Academic Bone Radiologists.

The diagnosis and management of chronic nonspinal osteomyelitis can be challenging, and guidelines regarding the appropriateness of performing percutaneous image-guided biopsies to acquire bone samples for microbiological analysis remain limited. An expert panel convened by the Society of Academic Bone Radiologists developed and endorsed consensus statements on the various indications for percutaneous image-guided biopsies to standardize care and eliminate inconsistencies across institutions. The issued statements pertain to several commonly encountered clinical presentations of chronic osteomyelitis and were supported by a literature review. For most patients, MRI can help guide management and effectively rule out osteomyelitis when performed soon after presentation. Additionally, in the appropriate clinical setting, open wounds such as sinus tracts and ulcers, as well as joint fluid aspirates, can be used for microbiological culture to determine the causative microorganism. If MRI findings are positive, surgery is not needed, and alternative sites for microbiological culture are not available, then percutaneous image-guided biopsies can be performed. The expert panel recommends that antibiotics be avoided or discontinued for an optimal period of 2 weeks prior to a biopsy whenever possible. Patients with extensive necrotic decubitus ulcers or other surgical emergencies should not undergo percutaneous image-guided biopsies but rather should be admitted for surgical debridement and intraoperative cultures. Multidisciplinary discussion and approach are crucial to ensure optimal diagnosis and care of patients diagnosed with chronic osteomyelitis.

18F-FDG PET imaging for treatment response assessment and management guidance in patients with skull base osteomyelitis.

OBJECTIVE: The objective of this study is to evaluate the role of hybrid 18F-FDG PET for treatment response assessment and management guidance in patients with skull base osteomyelitis. MATERIALS AND METHODS: Retrospectively, 33 patients, with at least a baseline and follow-up PET (computed tomography/MRI) scan, were included. Parameters like standardized uptake value (SUV) max, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) (initial, follow-up, percentage change) were analysed and outcomes based on 18F-FDG PET reports were classified into resolution (a), partial response (b), progression (c) and stable disease (d). The clinical course and response on anatomical imaging were also compared with 18F-FDG PET. RESULTS: There was mild correlation between initial SUV with ESR (0.338) and CRP (0.384). Moderate correlation was seen between follow-up SUV and CRP (0.619), percentage change in SUV max (PC SUV) with percentage change in ESR (0.456) and CRP (0.668). Mean PC SUV was 70% (a), 35% (b), -40% (c) and -18% (d), respectively. 48% (16/33) (resolution, progression, stable disease) patients had clear management change with 18F-FDG PET with either escalation or stopping of antibiotics/antifungals. Management decision in partial response group (52%, 17/33) was taken clinically. On retrospective PC SUV analysis, treatment continuation group (8 patients) showed 20% decrease, whereas the group that was only monitored further (9 patients) had 48% reduction in SUV. CONCLUSION: 18F-FDG PET showed a moderate association with clinical markers used in follow-up of patients with skull base osteomyelitis and is a reliable investigation for assessment of disease status. This can be used as a guide along with clinical evaluation for de-escalation of treatment.

Neonatal Osteomyelitis.

Osteomyelitis is a serious and potentially life-threatening condition affecting the skeletal system of newborns. The condition is relatively rare in neonates but occurs at higher rates in high-risk pregnancies, in preterm infants, and with the use of invasive devices. As a result of the anatomy and immature immune system of newborns, neonates differ in presentation, diagnosis, and management of osteomyelitis compared to patients of other age groups. An understanding of these differences will assist clinicians in the prompt diagnosis and management of this neonatal infection and lead to improved long-term outcomes.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Chronic infective arthritis with osteomyelitis of the ankle due to Pseudomonas aeruginosa infection in a middle-age woman: A rare causative pathogen requiring vigilance.

RATIONALE: Pseudomonas aeruginosa-induced septic arthritis is a relatively uncommon phenomenon. It has been documented in children with traumatic wounds, young adults with a history of intravenous drug use, and elderly patients with recent urinary tract infections or surgical procedures. PATIENT CONCERNS: Fifty-nine year-old female had no reported risk factors. The patient sought medical attention due to a 6-month history of persistent pain and swelling in her right ankle. DIAGNOSES: Magnetic resonance imaging and a 3-phase bone scan revealed findings suggestive of infectious arthritis with concurrent osteomyelitis. Histopathological examination of the synovium suggested chronic synovitis, and synovial tissue culture confirmed the presence of P aeruginosa. INTERVENTION: Arthroscopic synovectomy and debridement, followed by 6 weeks of targeted antibiotic therapy for P aeruginosa. OUTCOMES: Following treatment, the patient experienced successful recovery with no symptom recurrence, although she retained a mild limitation in the range of motion of her ankle. LESSONS: To our knowledge, this is the first reported case of chronic arthritis and osteomyelitis caused by P aeruginosa in a patient without conventional risk factors. This serves as a crucial reminder for clinicians to consider rare causative organisms in patients with chronic arthritis. Targeted therapy is imperative for preventing further irreversible bone damage and long-term morbidity.

Non-vertebral Mycobacterium avium complex osteomyelitis in an immunocompetent patient.

Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.

Electron Aggregation and Oxygen Fixation Reinforced Microwave Dynamic and Thermal Therapy for Effective Treatment of MRSA-Induced Osteomyelitis.

Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2O3/Fe3S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2O3/Fe3S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2O3/Fe3S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2O3/Fe3S4 displays a larger electromagnetism field enhancement parameter than Fe2O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2O3/Fe3S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.

Bacteriophage therapy and current delivery strategies for orthopedic infections: A SCOPING review.

OBJECTIVES: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized. METHODS: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central. RESULTS: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described. CONCLUSIONS: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.

Navigating the Enigma of Pediatric Musculoskeletal Infections: A Race Against Time.

Musculoskeletal infection (MSKI) in children is a critical condition in pediatric orthopedics due to the potential for serious adverse outcomes, including multiorgan dysfunction syndrome, which can lead to death. The diagnosis and treatment of MSKI continue to evolve with advancements in infectious organisms, diagnostic technologies, and pharmacologic treatments. It is imperative for pediatric orthopedic surgeons and medical teams to remain up to date with the latest MSKI practices.

Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.