Aberrant Expression of SLC7A11 Impairs the Antimicrobial Activities of Macrophages in Staphylococcus Aureus Osteomyelitis in Mice.

Staphylococcus aureus (S. aureus) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b+F4/80+ macrophages, and validated a predominant distribution of SLC7A11 in F4/80+ cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo. Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis.

Cat-scratch disease: a rare cause of osteomyelitis.

Cat-scratch disease is a zoonosis caused by Bartonella henselae, characterised by regional lymphadenopathy. Rarer presentations, such as osteomyelitis, can occur.We present an adolescent girl with severe right lumbar pain and fever, without animal contacts or recent travels. On examination, pain on flexion of torso, movement limitation and marked lordosis were noted, but there were no inflammatory signs, palpable masses or lymph nodes. Serological investigations revealed elevated inflammatory markers. Imaging revealed a paravertebral abscess with bone erosion. Several microbiological agents were ruled out. After a second CT-guided biopsy, PCR for Bartonella spp was positive. At this point, the family recalled having a young cat some time before. Cat-scratch disease was diagnosed, and complete recovery achieved after treatment with doxycycline and rifampicin.Cat-scratch disease is a challenging diagnosis in the absence of typical features. However, B. henselae must be investigated if common pathogens are ruled out and response to therapy is poor.

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.

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Causal associations between human gut microbiota and osteomyelitis: a Mendelian randomization study.

Background: Recent studies have emphasized the role of gut microbiota in the onset and progression of osteomyelitis. However, the exact types of gut microbiota and their mechanisms of action remain unclear. Additionally, there is a lack of theoretical support for treatments that improve osteomyelitis by altering the gut microbiota. Methods: In our study, we utilized the largest genome-wide association study (GWAS) meta-analysis to date from the MiBioGen consortium, involving 13,400 participants. The GWAS data for osteomyelitis were sourced from the UK Biobank, which included 4,836 osteomyelitis cases and 486,484 controls. We employed a two-sample Mendelian randomization framework for a detailed investigation into the causal relationship between gut microbiota and osteomyelitis. Our methods included inverse variance weighting, MR-Egger, weighted median, and weighted mode approaches. Additionally, we applied Cochran's Q statistic to assess the heterogeneity of the instrumental variable. Results: At the class level, Bacilli and Bacteroidia were positively correlated with the risk of osteomyelitis. At the order level, only Bacteroidales showed a positive association with osteomyelitis. At the genus level, an increased abundance of Butyricimonas, Coprococcus3, and Tyzzerella3 was positively associated with the risk of osteomyelitis, whereas Lachnospira was negatively associated. Sensitivity analyses showed no evidence of heterogeneity or pleiotropy. Conclusion: This study reveals that classes Bacilli and Bacteroidia, order Bacteroidales, and genera Butyricimonas, Coprococcus3, and Tyzzerella3 are implicated in increasing the risk of osteomyelitis, while the genus Lachnospira is associated with a reduced risk. Future investigations are warranted to elucidate the precise mechanisms through which these specific bacterial groups influence the pathophysiology of osteomyelitis.

Management of Chronic Osteomyelitis and Antibiotic Stewardship; An Effort to Delay the Post-Antibiotic Era.

OBJECTIVE: To develop an effective antimicrobial strategy for the management of chronic osteomyelitis. STUDY DESIGN: Observational study. Place and Duration of the Study: Departments of Microbiology and Orthopaedics, Combined Military Hospital Malir, Karachi, Pakistan, from January 2021 to February 2022. METHODOLOGY: Bone biopsies of 45 enrolled participants were taken for microbiological evaluation. Intravenous antibiotic therapy was begun as per empirical therapy based on the local antibiogram and antibiotic policy. Once the susceptibility pattern was available, targeted therapy started and continued for 28 to 42 days. Patients were evaluated based on inflammatory markers and clinical conditions for a minimum of six months to a maximum of one year. RESULTS:  Out of the 45 patients, the majority 29% were soldiers, 40% belonging to the age group of 31-60 years. The common predisposing factor was trauma/fractures followed by diabetes and implants leading to chronic sinus discharge and decubitus ulcers. The most commonly isolated organism was Staphylococcus aureus (38%) followed by Methicillin-resistant Staphylococcus aureus (MRSA) (31%). Cotrimoxazole and Rifampicin turned out to be good treatment options. Only 4.4% showed unsatisfactory prognosis, nonetheless, no mortality was observed during the course of treatment. CONCLUSION: In this study, highly resistant strains were observed with limited treatment options for chronic osteomyelitis, however, effective stewardship programmes with accurate diagnostic reporting and judicious use of antimicrobials can prevent overuse of the valuable resources. KEY WORDS: Antimicrobial stewardship, Osteomyelitis, Methicillin-resistant Staphylococcus aureus, Empirical therapy, Antimicrobial resistance.

Extended-Spectrum Beta-Lactamase Escherichia coli Diabetic Foot Osteomyelitis Causing Sausage Toe Deformity: Successful Therapy with Ertapenem in the Outpatient Setting.

BACKGROUND Diabetic foot osteomyelitis is a high-morbidity and debilitating complication of diabetic foot ulcers that contributes to significantly worse quality of life in the affected population and higher cost of healthcare services. One of the clinical presentations of diabetic foot osteomyelitis is the 'sausage' toe deformity, which affects the phalanges (local soft tissue infection and underlying bony changes). This deformity is highly suggestive of the presence of osteomyelitis. Unfortunately, during recent years, the emergence of antibiotic-resistant bacteria have created great difficulties in choosing appropriate empirical antibiotics for the treatment of diabetic foot infections. Multidrug-resistant pathogens have been strongly related to higher morbidity and mortality compared with infections caused by their antibiotic-susceptible counterparts. CASE REPORT We describe a case of a 74-year-old woman with long-standing insulin-treated type 2 diabetes, who experienced extended-spectrum beta-lactamase-producing Escherichia coli infection that caused diabetic foot osteomyelitis with 'sausage' deformity in her second right toe. She was successfully treated with surgical debridement combined with the administration of ertapenem in the outpatient setting, completing, in total, a 6-week course of antibiotic therapy. CONCLUSIONS 'Sausage' toe deformity is one of the clinical presentations of diabetic foot osteomyelitis, and should be an alarming sign in everyday clinical practice. Ertapenem is an excellent option for the treatment of diabetic foot infections caused by extended-spectrum beta-lactamase E. coli in the outpatient setting. Early diagnosis and proper therapeutic approach are of great importance to reduce the risk of amputations, overall mortality, total cost, and the surge of antimicrobial resistance in the community.

Deoxynivalenol and fumonisin predispose broilers to bacterial chondronecrosis with osteomyelitis lameness.

Bacterial chondronecrosis with osteomyelitis (BCO) lameness is the most critical animal health and welfare issue facing the broiler industry worldwide. It is estimated that 1 to 2% of bird condemnation at marketing age is caused by BCO lameness, resulting in tens of millions of dollars in annual losses. Fast-growing broilers are prone to mechanical stress that triggers bacterial translocation across epithelial barriers into the bloodstream, followed by bacterial colonization in the growth plate of long bones, and eventually, bone necrosis and lameness. Mycotoxins (MTX) are secondary metabolites produced naturally by microfungi, of which deoxynivalenol (DON), fumonisin (FUM), and zearalenone are the most prevalent in corn and soybean-meal-based diets. The presence of these mycotoxins in feed has been proven to reduce the barrier strength of the intestinal tracts and trigger immunosuppressive effects. In this study, we investigated the effects of the DON and FUM-contaminated feeds on the incidence of BCO lameness in broilers reared in both wire- and litter-floors. 720 one-day-old broiler chicks were assigned to the 2 × 2 factorial design: 2 MTX diets containing DON and FUM on wire flooring (MTX-W) and litter flooring (MTX-L), and 2 diets without MTX contamination on control wire flooring (CW) and control litter flooring (CL). Throughout the trial, the cumulative incidence of lameness per treatment was assessed by necropsying the lame birds. Birds in the MTX-W group had a higher incidence of lameness compared to those in CW (73.3% vs. 62.0%) (P < 0.05), and birds in the MTX-L group had a higher incidence of lameness compared to birds in CL (54.0% vs. 34.0%) (P < 0.05). MTX elicited net increases in BCO to a greater degree on litter (+20%) than on wire flooring (+12%). The increased incidence of BCO lameness in the MTX-W coincided with increased intestinal permeability supporting a correlation between intestinal barrier integrity and BCO lameness. To conclude, DON and FUM are predisposing factors for increasing BCO. However, no significant interaction exists between the diet and floor types in inducing lameness in broilers.

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.

Inducing experimental bacterial chondronecrosis with osteomyelitis lameness in broiler chickens using aerosol transmission model.

Lameness disease attributed to bacterial chondronecrosis with osteomyelitis in broilers affects production, animal welfare, and food safety in the poultry industry. The disease is characterized by necrotic degeneration of the rapidly growing femora and tibiae due to bacterial translocation from the respiratory or gastrointestinal tracts into the blood circulation, eventually colonizing the growth plate of the long bones. To investigate the etiology, pathogenesis, and intervention measures for BCO, developing an experimental model that reliably induces BCO lameness is of the utmost importance. In the past, we have employed a wire-flooring model and a litter-flooring model administered with a bacterial challenge to investigate strategies for mitigating BCO. However, multiple issues on labor-intensive barn setup and cleanout efforts for the wire-flooring system and concern of direct pathogenic exposure to the broilers for the litter-flooring models rendered these research models less effective. Thus, we investigated a new approach to induce experimental BCO lameness using an aerosol transmission model employing a group of birds reared on wire-flooring pens as a BCO infection source, and the disease is further disseminated through the airborne transmission to other birds reared on litter flooring in the same housing environment. The effectiveness of the aerosol transmission model in inducing BCO lameness was concluded from 4 independent experiments. The cumulative lameness generated from the BCO source group on the wire floors versus negative control treatments on the litter floors from Experiments 1, 2, 3, and 4 were 84% vs. 69.33%, P = 0.09; 54.55% vs. 60%, P = 0.56; 78% vs. 73.50%, P = 0.64; 81% vs. 74.50%, P = 0.11. Overall, the cumulative lameness generated from the wire floors was successfully transmitted to the birds on litter floors without significant statistical differences (P > 0.05). The effectiveness of the aerosol transmission model for experimentally triggering BCO lameness provides a reliable system for evaluating practical intervention strategies for BCO lameness in broilers.

Reconstructive surgery with an autologous bone graft in a dog with presumptive chronic non-bacterial osteomyelitis.

A 15-year-old Cocker Spaniel was referred to for the evaluation of left forelimb lameness. Radiographic and computed tomography examinations revealed osteolysis of the proximal left third, fourth and fifth metacarpal bones and pathological fractures of the proximal left fourth metacarpal bone. Histopathological examination via bone biopsy did not provide a definitive diagnosis, and the owner elected limb-sparing surgery. The fourth metacarpal bone and digits were amputated. Subsequently, autologous bone grafts were performed on the lytic area of the third and fifth metacarpal bones. The dog showed improvement in gait 7 weeks after reconstructive surgery. Chronic non-bacterial osteomyelitis (CNO) was diagnosed by exclusion. To the best of our knowledge, CNO has not been previously reported in dogs.

Empyema necessitans caused by methicillin-resistant Staphylococcus aureus: a case report and literature review.

BACKGROUND: Empyema necessitans (EN) is a rare condition characterized by pleural infection with pus spreading into adjacent soft tissues. Although Mycobacterium tuberculosis and Actinomyces israelii are common causative agents, methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare, but it is associated with high mortality in empyema cases. We aimed to report a unique case of EN caused by MRSA and present a literature review to better understand this rare condition. CASE PRESENTATION: A 69-year-old man with a history of right ureteral stone presented with fever and left anterior thoracic pain. A physical examination revealed redness and swelling in the left thoracic region. Imaging studies confirmed EN with fluid accumulation around the sternocostal joint of the left first rib. MRSA was identified from blood and pleural fluid cultures. The patient received antimicrobial therapy, and a chest tube was inserted for drainage. Despite initial improvement, vertebral osteomyelitis was diagnosed on day 17. The antimicrobials were subsequently terminated after 6 weeks, but vertebral osteomyelitis recurred, and treatment was resumed and completed on day 215. CONCLUSION: EN caused by MRSA is rare, and the literature review revealed 14 cases from human sources. Positive blood cultures were observed in 40% of cases, and metastatic infections were present in 30% of cases. Osteomyelitis was the most common type of metastatic lesion. All the patients underwent drainage. Patients with MRSA-associated EN frequently develop disseminated lesions and should therefore be carefully examined. Moreover, appropriate treatment with antibiotics and drainage is necessary for a good prognosis. Although the prognosis appeared to be favorable in our review, publication bias and treatment challenges for metastatic infections should be considered.

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.

Injectable Nano-Micro Composites with Anti-bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis.

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

Acute Hematogenous Osteomyelitis of the Pelvis in Children.

BACKGROUND: Pelvic involvement has been reported in 3%-14% of acute hematogenous osteomyelitis (AHO) cases in children. One guideline suggests need for a longer antibiotic course in pelvic AHO, however, recent data are lacking. We describe the clinical course of children with pelvic AHO and compare it to nonpelvic AHO. METHODS: A retrospective review of patients with a diagnosis of AHO admitted to Texas Children's Hospital from January 2012 to December 2020 was conducted. Patients 6 months-<19 years old and with ≤14 days of symptoms at admission were eligible. Patients with sickle cell disease or immunocompromised were excluded. Wilcoxon rank-sum test assessed for differences between continuous variables and Fisher exact for categorical variables using STATA 17. RESULTS: We compared 104 cases of pelvic AHO to 314 cases of nonpelvic AHO. Patients had similar microbiology, length of stay and length of antibiotic therapy. Patients with pelvic AHO had pyomyositis identified by magnetic resonance imaging more often (28.8 vs. 9.4%, P < 0.001) and bone abscess less often (22.1 vs. 46.5%, P < 0.001). Rates of chronic complications were comparable between patients with pelvic AHO and nonpelvic AHO (8.4% vs. 15.1%, P = 0.1). Nineteen patients (18.3%) with pelvic AHO received ≤30 antibiotic days without complications, but they had less need for intensive care or bone abscesses than patients treated longer. CONCLUSIONS: Pelvic AHO in children may be more frequent than previously reported but is not associated with more complications. Four weeks of therapy may be sufficient in selected patients. Prospective studies to compare outcomes with different lengths of therapy are needed.

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.].

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service.

PURPOSE: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. METHODS: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. RESULTS: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. CONCLUSION: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.

Clinical outcomes and complications of S53P4 bioactive glass in chronic osteomyelitis and septic non-unions: a retrospective single-center study.

INTRODUCTION: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical study, we described the efficacy and safety profile of surgical debridement and local application of S53P4 bioactive glass (S53P4 BAG) in the treatment of bone infections. METHODS: A consecutive single-center series of 38 patients with chronic osteomyelitis (24) and septic non-unions (14), treated with bioactive glass S53P4 as dead space management following surgical debridement between May 2015 and November 2020, were identified and evaluated retrospectively. RESULTS: Infection eradication was reached in 22 out of 24 patients (91.7%) with chronic osteomyelitis. Eleven out of 14 patients (78.6%) with septic non-union achieved both fracture healing and infection healing in 9.1 ± 4.9 months. Three patients (7.9%) developed prolonged serous discharge with wound dehiscence but healed within 2 months with no further surgical intervention. Average patient follow-up time was 19.8 months ± 7.6 months. CONCLUSION: S53P4 bioactive glass is an effective and safe therapeutic option in the treatment of chronic osteomyelitis and septic non-unions because of its unique antibacterial properties, but also for its ability to generate a growth response in the remaining healthy bone at the bone-glass interface.