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.

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.

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.

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.

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.

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.

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.

Reconstructive endovascular treatment of petrous ICA pseudoaneurysm in skull base osteomyelitis: a hidden catastrophe.

Skull base osteomyelitis can be more life-threatening in immunocompromised patients and patients with diabetes. Here, we present a case of a petrous internal carotid artery pseudoaneurysm resulting from skull base osteomyelitis in a diabetic male in his 50s. This case report highlights the need to be conscious of the various complications associated with skull base osteomyelitis, be proficient in detecting them and treat them as early as possible for better outcomes. After adequate control of the disease process with medical treatment, immediate management of the aneurysm with balloon angioplasty and stenting was done. Acknowledging the trivial nasal and ear bleed, radiological evaluation is necessary to rule out rare complications like pseudoaneurysms in a diagnosed case of skull base osteomyelitis. In the discussion, we have cited the various treatment methods and similar cases of pseudoaneurysm caused by osteomyelitis. Currently, the patient continues to live a disease and disability-free life.

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.

Atypical Mycobacterial Infections of the Spine: Evaluation and Management.

BACKGROUND: Atypical mycobacterial infections of the spine can be difficult to treat and represent a subset of the vertebral osteomyelitis and diskitis spectrum often requiring early and aggressive surgical intervention. The purpose of this review is to improve the understanding of and approach to disease management from the perspective of the spine surgeon. MATERIALS AND METHODS: Debridement or excision of the affected levels may be necessary to decrease mycobacterial loads and restore biomechanics. A close relationship with the patient's internal medicine and infectious disease specialists should be maintained to ensure disease eradication or remission. Long-term suppressive antibiotic therapy may be required for infection control. RESULTS AND CONCLUSION: Atypical mycobacterial spine infections are rare, complex, and difficult to eradicate. Our institution proposes a collaborative effort among the spine surgeon, infectious disease specialists, and internal medicine specialists to best approach the work-up, diagnosis, and treatment of these infections. [Orthopedics. 2024;47(2):e61-e66.].

Use of hyperbaric oxygen therapy to treat a pressure ulcer complicated by osteomyelitis: a case report.

The development of a pressure ulcer (PU) following hospitalisation and immobility can lead to more severe complications, such as osteomyelitis. We report the case of a 60-year-old female patient with a PU complicated with osteomyelitis who was treated with hyperbaric oxygen therapy (HBOT). The patient was diagnosed with an unstageable PU according to the European Pressure Ulcer Advisory Panel classification. A total of 35 HBOT sessions were administered to manage her condition. HBOT is considered a safe and effective treatment for osteomyelitis and decreases mortality rate.

Outcome of Chronic Foot Osteomyelitis Treated With Hyperbaric Oxygen: An Observational Study.

Chronic refractory osteomyelitis of the foot stands as a formidable challenge in medical care, associated with significant morbidity and escalating healthcare costs. Traditional therapeutic approaches, including surgical debridement and systemic antibiotics, often fall short, leaving patients and clinicians in search of more efficacious interventions. Hyperbaric oxygen therapy (HBOT), an innovative therapeutic modality, has recently emerged as a promising adjunct therapy, offering a beacon of hope in this therapeutic conundrum. In this groundbreaking observational study, we meticulously analyzed the experiences of 80 patients suffering from chronic refractory osteomyelitis of the foot. Following surgical debridement and tailored antibiotic therapy, each patient was treated with HBOT at 2.5 atmospheres absolute for 120 min, 5 days a week, spanning an average of 50 days. Our primary endpoints focused on complete eradication of infection, recurrence metrics, and any adverse effects linked to HBOT. Astonishingly, 68 of the 80 patients (85%) achieved a total infection clearance, maintaining this status through a mean follow-up period of 36 months, all without a single report of HBOT-induced complications. Our compelling findings advocate that HBOT, synergized with standard surgical and antibiotic regimens, can revolutionize the treatment landscape for chronic refractory osteomyelitis of the foot. Given these promising preliminary results, there's an imperative need for extensive research to delineate the long-term advantages and to fine-tune HBOT protocols, potentially paving the way for a new therapeutic gold standard.

Interventions in the management of diabetes-related foot infections: A systematic review.

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

A Smart Bacteria-Capture-Killing Vector for Effectively Treating Osteomyelitis Through Synergy Under Microwave Therapy.

Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.

Treatment of Spinal Infections.

The treatment of spinal infections is not well defined, and a cursory review of the literature can lead to conflicting treatment strategies. To add to the complexity, infections can include primary infection of the spine, infection secondary to another primary source, and postoperative infections including epidural abscesses, discitis, osteomyelitis, paraspinal soft-tissue infections, or any combination. Furthermore, differing opinions often exist within the medical and surgical communities regarding the outcomes and effectiveness of varying treatment strategies. Given the paucity of defined treatment protocols and long-term follow-up, it is important to develop multidisciplinary treatment teams and treatment strategies. This, along with defined protocols for the treatment of varying infections, can provide the data needed for improved treatment of spinal infections.

Musculoskeletal Infection: Role of Molecular Imaging in Diagnosis and Monitoring Treatment Response.

Molecular imaging tests frequently are performed as part of the diagnostic workup of musculoskeletal infection. Three-phase bone scintigraphy reliably diagnoses osteomyelitis in bones not affected by underlying conditions. The test is less useful, because of decreased specificity, in patients with underlying bony abnormalities or alterations such as fractures, orthopaedic hardware, arthritic changes, and tumors. At one time gallium-67 scintigraphy was used as a complement to bone scintigraphy to improve the specificity of diagnosis. With the introduction of labeled leukocytes and, more recently, fluorine-18 fluorodeoxyglucose, gallium-67 is reserved primarily for spinal infections when fluorine-18 fluorodeoxyglucose is not available. Except for the spine, in vitro labeled leukocyte imaging is valuable for diagnosing osteomyelitis in the setting of underlying osseous abnormalities. Leukocytes accumulate in bone marrow as well as in the presence of infection. Performing complementary bone marrow imaging with technetium-99m sulfur colloid facilitates the differentiation between the two and improves test accuracy. Fluorine-18 fluorodeoxyglucose accurately diagnoses spondylodiskitis and diabetic foot osteomyelitis, but its value in periprosthetic joint infection has yet to be determined.

68 Ga-Citrate PET/CT Imaging in the Diagnosis of Skull Base Osteomyelitis and Its Usefulness in the Assessment of Treatment Response.

PURPOSE: 68 Ga-citrate PET/CT imaging in the diagnosis of skull base osteomyelitis (SBO) and its usefulness in the assessment of treatment response. METHODS: Eighteen patients underwent 68 Ga-citrate PET/CT scans for suspected SBO for diagnosis/assessment of treatment response. RESULTS: Of 18 patients, 16 patients had a positive study for SBO, and 2 patients had a negative study. Scan findings were correlated with clinical, biochemical, microbiological, and radiological parameters. CONCLUSION: 68 Ga-citrate PET/CT is a promising tool in the diagnosis and management of skull base osteomyelitis.

Absceso de Brodie en la clavícula: una forma poco frecuente de presentación / Brodie abscess in the clavicle: an uncommon presentation

La osteomielitis (OM) se define como la inflamación ósea de origen infeccioso. La forma aguda es frecuente en la edad pediátrica. El absceso de Brodie es un tipo de osteomielitis subaguda, históricamente con baja incidencia, pero que actualmente se presenta un aumento de la misma. De poca repercusión clínica, con pruebas de laboratorio inespecíficas y estudios radiológicos de difícil interpretación, es crucial la sospecha diagnóstica. Se asemeja a procesos neoplásicos, benignos o malignos. Recae en la experiencia del profesional realizar el diagnóstico adecuado. El tratamiento consiste en antibioticoterapia, tanto parenteral como por vía oral, y eventualmente drenaje quirúrgico. Presentamos una paciente sana que consultó por una tumoración en topografía de clavícula izquierda de 3 meses de evolución. Se realizó diagnóstico de absceso de Brodie, inició tratamiento y se obtuvo una buena respuesta. Resulta imprescindible tener un alto índice de sospecha de esta entidad para no someter al paciente a estudios, pruebas invasivas o tratamientos erróneos, y evitar secuelas a futuro.

Osteomyelitis is defined as an inflammation of the bone caused by infection. Acute osteomyelitis is common in pediatrics. A Brodie abscess is a type of subacute osteomyelitis, with a historically low incidence; however, its incidence is currently increasing. Given its little clinical impact, with non-specific laboratory tests and radiological studies of difficult interpretation, diagnostic suspicion is crucial. It resembles neoplasms, either benign or malignant. An adequate diagnosis falls on the health care provider's experience. Treatment consists of antibiotics, both parenteral and oral, with potential surgical drainage. Here we describe the case of a healthy female patient with a tumor found in the topography of the left clavicle 3 months before. She was diagnosed with Brodie abscess; treatment was started with a good response. A high index of suspicion of Brodie abscess is critical to avoid invasive tests and studies or inadequate treatments, and to prevent future sequelae.

First report of successful treatment of chronic pediatric tibial osteomyelitis and fracture using autologous platelet-rich plasma.

Osteomyelitis is a refractory disease caused by microbial invasion of the bone, leading to destruction of the bone tissue. It is more common in children. Osteomyelitis requires long treatment at high cost and is associated with high rates of recurrence and disability. It can also be complicated by sepsis that, if not treated in time, can result in death. Here, we report the first case of a 10-year-old patient who presented with chronic tibial osteomyelitis complicated with fracture. The patient had received traditional treatment for osteomyelitis for over 14 months without success. However, after 4 months of treatment with autologous platelet-rich plasma, the fracture, infection, and osteomyelitis resolved completely. These clinical observations demonstrate the potential for using autologous platelet-rich plasma as a novel treatment for chronic pediatric osteomyelitis.