Introduction. Wide, tumor-like resection for chronic osteomyelitis (COM), a standard practice previously, has been challenged recently with adequate, local debridement. This paper reviews the evolution of surgical debridement for long bone osteomyelitis, and presents the outcome of adequate debridement in a tertiary bone infection unit. Materials & Methods. Retrospective review of records from 2014 to 2020 of patients with long bone osteomyelitis. All records were searched electronically and imaging reviewed. All patients were managed by Multidisciplinary Infection Team protocol. Results. 53 patients (54 bones) with median age of 45.5 years (IQR 31 to 55) and mean follow-up of 29 months (12 – 59) were identified. According to Cierny-Mader classification, ten bones were type I, 39 were type III, and five were type IV; via the BACH classification of long bone osteomyelitis 21 were uncomplicated, 32 were complex, and one had limited options. All patients were treated with single-staged management with one planned second stage stabilization. Seventy-five percent grew positive microbial cultures. Forty-six (85%) cases had resolution of COM after index procedure and 51 (94%) had resolution at last follow up. Four (7%) patients underwent second surgical procedure and six (11%) patients had complications. Conclusions. We report high COM resolution rate through detailed pre operative evaluation and planning with multidisciplinary team approach. We challenge the need for wide tumor-like resection and the need for regenerative procedures in all cases of COM. Adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes

Aims. The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods. We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results. A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion. We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement. Cite this article: Bone Jt Open 2023;4(8):643–651

Aim. To investigate self-reported quality of life (QoL) in patients with osteomyelitis referred to a specialist centre in the UK and investigate the relationship between QoL and BACH classification. Method. All patients newly referred to a specialist bone infection clinic at a single tertiary centre within the UK between January 2019 and February 2020 were prospectively included. Diagnosis of osteomyelitis was made according to the presence of clinical and radiological criteria for ≥6 months. An EQ-5D-5L questionnaire and visual analogue score (VAS) were completed during the initial clinic appointment. Long-bone osteomyelitis was classified by the attending orthopaedic surgeon using the BACH classification system as either uncomplicated, complex or with limited options available.1 Patients managed non-operatively were subclassified into those who were (i) unfit to receive an operation or (ii) fit and well with stable disease. EQ-5D index scores were compared to a published UK value set of 41 chronic health conditions within the UK.2. Results. 201 patients were referred during the study period, with 159 (79.1%) patients diagnosed with long-bone osteomyelitis and 16 (8.0%) with osteomyelitis of the pelvic bones. Patients with pelvic osteomyelitis reported lower EQ-5D index scores compared to long-bone osteomyelitis (EQ-5D: 0.097 vs. 0.435, p<0.001) but similar VAS (60.2 vs. 54.6, p=0.37). Long-bone and pelvic osteomyelitis gave the 40th and 41st lowest EQ-5D scores respectively when compared to 41 other chronic health conditions including stroke, chronic obstructive pulmonary disease, kidney disease, liver disease and malignancy. Patients classified as having uncomplicated long-bone osteomyelitis reported significantly higher QoL compared to those classified as complex osteomyelitis (EQ-5D: 0.527 vs. 0.401, p<0.05; VAS: 66.9 vs. 58.4, p<0.05). Patients who were not fit for surgery due to co-morbidity reported similar QoL scores compared to those patients with complex osteomyelitis (EQ-5D: 0.293, p=0.07; VAS: 46.6, p=0.06). Patients with stable disease who did not require surgery, gave significantly better QoL scores when compared to the other classifications of osteomyelitis (EQ-5D: 0.746, p<0.01; VAS: 81.9, p<0.01). Conclusions. Patient reported QoL in osteomyelitis correlates with disease complexity as classified according to the BACH classification system. Patients with pelvic and long-bone osteomyelitis rate their QoL lower than patients with other chronic diseases

Introduction. Open tibial fractures (OTF) rank first among lower limb fractures in sub-Saharan Africa and bone infection remains the main challenge. The aim of this study was to identify the factors associated with chronic bone infection after OTF in a limited-resource setting. Methods. Patients aged 18 years and older, who underwent OTF treatment in a tertiary care hospital during the period from December 2015 to December 2020 were included in this retrospective study. Patients were contacted via phone calls and invited for a final clinical and radiological evaluation. Patients who met diagnostic criteria of chronic osteomyelitis were identified. Logistic regression was used to determine the predictive factors of OTF related chronic osteomyelitis. Results. With a mean follow-up period of 29.5±16.6 months, 33 patients out of 105 (31.4%) presented with chronic osteomyelitis. We found that time to first debridement within 6 hours (OR=0.18, 95% CI: 0.05 – 0.75, p=0.018) and severity of OTF according to Gustilo-Anderson classification (OR=2.06, 95% CI:1.34 – 3.16, p=0.001) were the independent predictive factors of chronic bone infection. Neither age, gender, socio-economic level, polytrauma, HIV status, diabetes mellitus, time to definitive surgery, were associated with chronic osteomyelitis. Conclusion. The rate of chronic bone infections after OTF is still high in the sub-Saharan African context. In addition to the overall improvement in the management of open leg fractures in those settings, emphasis should be placed on very early initial debridement to reduce the burden of these infections. Keys words. open tibial fractures, chronic bone infection, predictive factors

Aim. Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Method. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score. Results. 257 patients were referred, and 219 had suspected osteomyelitis. 196 patients had long bone infection and reported an average EQ-index score of 0.455 (SD 0.343). 23 patients with pelvic osteomyelitis had an average EQ-index score of 0.098 (SD 0.308). Compared to other chronic conditions, patients with long-bone osteomyelitis had worse QoL when compared to different types of malignancy (including bladder, oropharyngeal, colorectal, thyroid and myeloma), cardiorespiratory disease (including asthma, COPD and ischaemic heart disease), psychiatric conditions (including depression, pain and anxiety), endocrine disorders (including diabetes mellitus), neurological conditions (including Parkinson's disease, chronic pain and radiculopathy) and musculoskeletal conditions (including osteogenesis imperfecta, fibrous dysplasia and x-linked hypophosphataemic rickets). QoL in long-bone infection was similar to conditions such as Prada-Willi syndrome, Crohn's disease and juvenile idiopathic arthritis. Patients who had a history of stroke or multiple sclerosis reported worse QoL scores compared to long-bone infection. Patients who had pelvic osteomyelitis gave significantly lower QoL scores when compared to all other conditions that were available for comparison in the literature. In long bone infection, 41 cases (21.0%) were classified as ‘Uncomplicated’, 136 (69.4%) as ‘Complex’ and 19 (9.7%) as ‘Limited treatment options available’. Within classification stratification, patients with ‘Uncomplicated’ long bone infections reported a mean EQ-index score of 0.618 (SD 0.227) which was significantly higher compared to ‘Complex’ (EQ-index: 0.410 SD 0.359, p=0.004) and ‘Limited treatment options available’ (EQ-index: 0.400 SD 0.346, p=0.007). Conclusions. Bone and joint infections have a significant impact on patient quality of life. It is much worse when compared to other common chronic conditions, including malignancy, cardiovascular and neurological diseases. This has not been previously reported but may focus attention on the need for more investment in this patient group

Aim. Osteomyelitis (OM) is a debilitating infection of the bone that originates from hematogenous spreading of microbes or contamination after surgery/fracture. OM is mainly caused by the opportunistic bacterium Staphylococcus aureus (SA), which can evade the host immune response, acquire antibiotic resistance and chronically colonize the musculoskeletal tissue . 1,2. , yet the underlying molecular and cellular processes are largely unclear. This study aimed to characterize the pathogenetic mechanisms of SA-OM with a focus on the long pentraxin 3 (PTX3), a soluble pattern recognition molecule and bone tissue component that is emerging as a new player in osteoimmunology . 3. and a diagnostic marker of periprosthetic joint infections, a common form of OM. 4. . Method. A murine model of OM based on intra-bone injection of SA was developed that closely mimicked surgery/trauma-related OM in humans and allowed addressing the role of PTX3 in gene-modified (Ptx3-/-) animals. Local and systemic infection and inflammation were assessed via microbiology, flow cytometry, histochemistry and microCT techniques. Results. SA-injected mice developed chronic infection with measurable levels of viable bone-resident bacteria up until 30 days from microbial challenge. The infection was confined to the treated limbs only and accompanied by extensive tissue remodelling. The bacterial load was higher in WT than Ptx3. -/-. animals at 6 and 14 days from SA injection. Accordingly, WT mice had enhanced systemic inflammation with expanded innate immune compartment in the spleen and increased serum levels of inflammatory cytokines and chemokines. PTX3 levels were higher in SA- than vehicle (PBS)-injected WT animals both in the serum and bone tissue. Furthermore, administration of a PTX3-targeting antibody reduced the bacterial burden in the bones of SA-injected WT mice. Conclusions. In a mouse model of SA-OM, genetic deficiency of PTX3 protected from infection and inflammation, pointing to this pentraxin as a crucial player in OM pathogenesis and a novel therapeutic target in bone infections. The study was approved by the Italian Ministry of Health (approval n. 520/2019-PR issued on 19/07/2019) and supported by Fondazione Beppe and Nuccy Angiolini

Aim. The liver is the major source of acute phase proteins (APPs) and serum concentrations of several APPs are widely used as markers of inflammation and infection. The aim of the present study was to explore if a local extra hepatic osseous acute phase response occurs during osteomyelitis. Method. The systemic (liver tissue and serum) and local (bone tissue) expression of several APPs during osteomyelitis was investigated with qPCR and ELISA in a porcine model of implant associated osteomyelitis (IAO) at 5, 10 and 15 days after inoculation with S. aureus or saline, respectively. Additionally, samples were also collected from normal heathy pigs and pigs with spontaneous, chronic, haematogenous osteomyelitis. Afterwards, immunohistochemistry towards different upregulated APPs was performed on the porcine osteomyelitis lesions and on bone biopsies from human patients with chronic osteomyelitis. Results. All infected porcine bone lesions (apart from Day 5 in the IAO model) were made up by necrosis, pus, and various degree of fibrotic encapsulation. A local, highly significant upregulation of Serum Amyloid A (SAA, up to 4000-fold upregulation), Complement component C3 (C3), and Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) were present in infected pigs compared to sterile controls. For the experimental IAO animals, the upregulation of C3 and ITIH4 increased over time, i.e., the highest expression was seen on day 15 after bacterial inoculation. In the liver, only C-reactive protein (CRP) and ITIH4 (not SAA or C3) were slightly upregulated in infected pigs. Serum concentrations of CRP, SAA and haptoglobin were only upregulated at day 5 in IAO infected animals. Immunohistochemically, comparable numbers of APP positive cells (leucocytes and bone cells) were found in human and porcine bone samples with chronic osteomyelitis. Conclusions. This is to our knowledge the first description of local APP up-regulation during chronic bone infection. Only small changes in the expression of APPs were found in the liver and serum samples. Thus, the presence of an osseous upregulation of APPs appears to be part of a predominantly local response that will be difficult to measure systemically. The importance of a local immune response in bone infections seems logical as the blood supply is severely impaired during osteomyelitis. There is a real need for supportive diagnostic bone infection criteria which should be based on a comprehensive understanding of the local inflammatory response. As seen from the present study, staining for SAA or C3 could potentially improve the diagnostic performance of histopathology

Introduction. Osteomyelitis (OM) is a challenging condition to diagnose and treat. The multidisciplinary team (MDT) approach is used in managing complex diseases such as cancer and diabetes. The Hull Regional Bone Infection MDT team was established to provide coordinated care for patients suspected to have OM. This study reviews the orthoplastic treatment and outcomes of patients with non-periprosthetic OM. Materials and Methods. Retrospective review of patients presenting to the MDT team who had orthoplastic intervention with debridement and flap coverage between 1/6/2014 - 30/11/2018. We describe our MDT approach of assessment, planning for surgical intervention and antibiotic protocol. Data was obtained from electronic and paper patient records, and PACS. Results. Twenty-nine patients were identified (75.9% male). Mean age was 52.7 (23–82). Median duration of symptoms at surgery was 10 months (IQR 4.0–34.3). Cierny-Mader (CM) Host Type B. (L). (41.4%), type B. (S). (34.5%), and type B. (S+L). (17.2%). Twenty-four patients (82.8%) were CM anatomical class IV. Twenty-four patients (82.8%) had single-stage surgical treatment. Twenty-one patients received 23 free flaps. Anterolateral thigh flap (9/23) and gracilis muscle flap (7/23) were most commonly used. Tibialis anterior flap was the most commonly used local flap. Stimulan was used in 65.5%. Staphylococcus aureus was seen in 60% of patients. Mean follow-up time was 21 months (1–62). There were 2 (6.9%) OM recurrence. Both patients were CM anatomical class IV. Conclusions. Our study showed that our MDT management of patients with OM can achieve a low recurrence rate despite a high proportion of patients with severe OM. We recommend considering an MDT approach for these complex OM patients

Aim. There are no definitive criteria for the definition of osteomyelitis in the hand and wrist and published case series are small. It remains a relatively uncommon, but difficult to treat problem. We present a series of 30 cases from 2016 to 2021 from a tertiary referral centre. We propose that the principles of thorough surgical debridement, dead space management, skeletal stabilisation and culture driven antibiotic therapy are the key to management of osteomyelitis in the hand and wrist. In addition, we show how these basic principles can be used for both functional and aesthetic impact for the wrist and digits with illustrated cases. Methods. We conducted a retrospective chart review over a 6 year period and recorded the site of the infection, the soft tissue and bony management, whether antibiotic eluting bone filler was used, the isolated bacterial species, the number of surgical procedures undertaken to treat the infection and the success rate for clearing the infection. Results. 17/30 cases had pre-existing metalwork in-situ. There were 19 phalangeal/metacarpal infections and 11 carpal infections. 24 patients had native joint involvement. A drug eluting bone void filler was used in 23/30 cases in order to manage the dead space. In 7/30 cases had polymicrobial organisms isolated, 15/30 had only one organism cultured. The most common organism cultured was Staphylococcus aureus. Complete resolution of osteomyelitis or joint infection was achieved in 29/30 cases with follow up ranging from six months to six years. 2/30 cases required thorough debridement of the distal phalanx; bone void filler provided an aesthetically optimal result to improve fingertip contour whilst managing the dead space. Conclusion. Osteomyelitis of the hand and wrist is optimally managed with thorough surgical debridement, dead space management with a drug eluting bone void filler, skeletal stabilisation and culture directed antibiotic therapy. In addition, the bone void filler provides pulp support and improves the aesthetic contour of fingertips in which distal phalangeal osteomyelitis was successfully treated

Aim. The osteolytic process of osteomyelitis is, according to textbooks, caused by increased osteoclast activity due to RANKL production by osteoblasts. However, recent findings contradict this theory. Therefore, the aim was to investigate, in a porcine osteomyelitis model, how osteolysis is affected by massive inflammation and RANKL blocking, respectively. In parallel, patients with chronic osteomyelitis, diabetes, foot osteomyelitis, and fracture related infections (FRI) were included for advanced histological analysis of osteolysis. Methods. In pigs, a tibial implant cavity was created and inoculated with 10. 4. CFU of Staphylococcus aureus: Group A (n=7). Group B (n=7); + 1cm. 3. spongostan into the cavity. Group C (n=4); + systemic Denosumab treatment. Spongostan was used as an avascular material to support bacterial growth and thus increase the inflammatory response. Denosumab treatment was administrated to suppress osteoclast activity by RANKL inhibition (as in osteoporotic patients). The volume of osteolysis was accessed by CT scans. Immunohistochemistry with antibodies towards Cathepsin K was used to identify osteoclasts within the bone lesions. Briefly, the number of Cathepsin K positive cells, i.e., both precursors and bone resorbing osteoclasts, respectively, were counted in 10 high power fields (400x). In total, 50 bone infection patients were included (Herlev Hospital). From each patient five parried samples were taken for histology and microbiology, respectively. Histopathology, CT osteolysis volume estimation, and molecular expression of osteoclasts and inflammatory markers are ongoing. One FRI patient was osteoporotic and treated with Denosumab for 6 years. Results. All pigs were confirmed infected in the implant cavity. The volume (2.41 ± 1.29cm. 3. ) of osteolysis was significantly increased in the spongostan group in comparison to Group A (1.24 ± 0.59 cm. 3. ) (p=0.04). Thereby, the spongostan group had bacteria deeper into the bone from the inoculation point. Sufficient Denosumab treatment, i.e. reduced serum Ca was seen in 3 pigs. None of the Denosumab treated pigs showed reduced osteolysis in comparison to Group A (1.42 ± 0.63 cm. 3. ). The Cathepsin K score of Group C was 17 (15-23 IQR) of precursor osteoclasts and 2 (0-2 IQR) of osteoclasts in Howship lacunae. The Denosumab treated patient showed substantial osteolysis and histological analysis confirmed acute inflammatory. Conclusions. Application of spongostan, i.e., bacterial host optimization and massive inflammation promotes osteolysis and local bacterial dissemination. Osteoclast blocking with Denosumab showed no impact on osteolysis. Elucidation of the pathophysiology causing bone loss in osteomyelitis is fundamental. However, the widely accepted osteoclast-based theory might not be the only relevant

Introduction. Osteomyelitis is a challenge in diagnosis and treatment. 18F-FDG PET-CT provides a non-invasive tool for diagnosing and localizing osteomyelitis with a sensitivity reaching 94% and specificity reaching 100%. We aimed to assess the agreement in identifying the geographic area of infected bone and planned resection on plain X-ray versus 18F-FDG PET-CT. Materials & Methods. Clinical photos and X-rays of ten osteomyelitis patients were shown to ten consultant surgeons; they were asked to draw the area of infection and extent of planned surgical debridement; data will be compared to 18F-FDG PET-CT results. Results. We tested the agreement between the surgeons in every parameter. Regarding height, there was poor agreement between surgeons. Regarding perimeter, the ten surgeons showed low-moderate agreement. The ten surgeons showed a low-moderate agreement for circularity. Results document the variability of assessment and judgement based on plain X-rays. In comparison to PET-CT, All parameters were significantly different in favour of 18F-FDG PET-CT over X-ray (P < 0.001). Conclusions. 18F FDG PET-CT provides a three-dimensional tool for localizing the exact location of the infected bone and differentiating it from the normal bone. Thus, it could be beneficial in precise pre-operative planning and surgical debridement of chronic osteomyelitis

Acute Haematogenous Osteomyelitis (AHO) remains a cause of severe illness among children. Contemporary research aims to identify predictors of acute and chronic complications. Trends in C-reactive protein (CRP) following treatment initiation may predict disease course. We have sought to identify factors associated with acute and chronic complications in the New Zealand population. A retrospective review of all patients <16 years with presumed AHO presenting to a tertiary referral centre between 2008–2018 was performed. Multivariate was analysis used to identify factors associated with an acute or chronic complication. An “acute” complication was defined as need for two or more surgical procedures, hospital stay longer than 14-days, or recurrence despite IV antibiotics. A “chronic” complication was defined as growth or limb length discrepancy, avascular necrosis, chronic osteomyelitis, pathological fracture, frozen joint or dislocation. 151 cases met inclusion criteria. The median age was 8 years (69.5% male). Within this cohort, 53 (34%) experienced an acute complication and 18 (12%) a chronic complication. Regression analysis showed that contiguous disease, delayed presentation, and failure to reduce CRP by 50% at day 4/5 predicted an acutely complicated disease course. Chronic complication was predicted by need for surgical management and failed CRP reduction by 50% at day 4/5. We conclude that CRP trends over 96 hours following commencement of treatment differentiate patients with AHO likely to experience severe disease

Aim. Intramedullary osteomyelitis remains a challenge in the treatment of bone infections, requires organized, sequential and effective management to prevent its spread and subsequent recurrence. Errors are often made in the comprehensive treatment of this type of infection classified as type 1 of Cierny-Mader, where you can perform an insufficient treatment or in some cases perform very extensive and unnecessary bone resections. A rigorous protocol is proposed, by stages to achieve the total eradication of the infection and a surgical tactic that avoids diffusion of the infection or recurrences. Method. In the prospective case series study, 16 patients with type 1 intramedullary infection of Cierny Mader, diagnosed by radiology, TAC or MRI were included. The microbiological protocol is carried out, with the germ typing and the corresponding antibiogram, at least 3 samples of deep tissues, the biofilm and segments of dead bone are taken. In the surgical tactic, intramedullary sequestrations are resected, the intramedullary canal is cleaned by stages, initially in the most inflammatory focus detected, the medullary canal is accessed through a planned and defined bone window, with round edges to avoid fractures and allowing access To the flexible reamer and cleaning guides, an additional window is made that avoids the blood dissemination of the infection, the septic embolisms or the contamination of the underlying soft tissues. It is defined if it requires stabilization of the bone with internal or external devices, therapies are applied locally to avoid recolonization, using Bioglass or absorbable substitutes with selective antibiotic. The treatment is associated with intravenous antibiotic therapy between 2 and 6 weeks according to the type of germ and if it is multiresistant. It guarantees skin coverage and protection of structures at risk such as nerves, tendons and exposed bone. Results. Successful treatment results are obtained, infection eradication in 100% of cases, the healing of osteomyelitis is achieved by applying an integral management of the intramedullary canal Osteomyelitis and a complete protocol is established. Conclusions. The tactic and surgical technique applied in the integral management of intramedullary bone infection is essential to obtain definitive results in the eradication of bone infection. Care must be taken that the debridement is complete of the intramedullary canal and additionally, segmental or exaggerated resection of viable bone must be avoided, which survives and heals after the integral management of the infection with effective antibiotic therapy

Introduction. Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis. Methods. Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers. Results. Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials. Conclusion. Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint

Aim. Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria. Method. 19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples. Results. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infectious samples as a common finding in both cell types. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number could be found as a sign for increased mitochondrial fission. Conclusions. The results show that mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This suggests that manipulation of mitochondrial dynamics in a way of inhibiting mitochondrial fission may improve bone cell survival and exploit bone cells regenerative potential to aid in the treatment of osteomyelitis

Aim. Melioidosis is a significant public health problem in endemic regions such as India. Lack of awareness, predominant empiric antibiotic use reducing culture yields, morphotypic variability of cultures and frequent misidentification by automated blood culture systems, pose myriad challenges in diagnosis and treatment. Through this series, we present our experience of Hematogenous Osteomyelitis with Burkholderia pseudomallei. Method. This was a single centre, retrospective, observational study performed at a tertiary case hospital in Mumbai, India from June 2011 to June 2021. Results. The study comprised of 7 cases (6:1, M: F). Mean age was 53.7 years (5 to 75). All had an underlying co- morbidity or were immunosuppressed. 3 patients were misidentified by automated systems prior to presentation (e coli, burkholderia cepacieae, acinetobacter). Most common site of infection was femur (n= 3), followed by tibia and foot and ankle (n= 2, each). One had disseminated meliodosis involving the spleen, lymph nodes, pulmonary) in addition to involvement of bilateral feet and ankles. B. pseudomallei was identified in all following surgical debridement at our institute. Each patient underwent mean 2 procedures. 3 needed local rotation flap surgeries for wound cover. All were treated with ceftazidime along with trimethoprim- sulfamethoxazole (TMP- SMX) during the 6 week induction phase. TMP- SMX was continued for a further 6 months in the consolidation phase. All patients had infection remission at a mean 19.3 months follow up. There were no mortalities in our series. Conclusions. Clinically Burkholderia infections mimic other pyogenic infections, Gram-negative sepsis, tuberculosis and has been referred to as the “remarkable imitator” and the “mimicker of maladies”. Diabetes and alcoholism are risk factors. The need for diagnosing this entity is due to the fact that the septicemic form has a mortality rate that exceeds 90%. Melioidosis is frequently misidentified. A high clinical suspicion, communication with microbiologist, knowledge about the biochemical, cultural and phenotypic susceptibility patterns may help in optimising diagnosis. Adequate debridement coupled with targeted prolonged antibiotics help achieve good outcomes

Aim. Local antibiotics, delivered to the site of infection, achieve high tissue concentrations and are used as an adjunct to systemic therapy. Local gentamicin provides levels well above the minimum inhibitory concentration and may be sufficient on its own, however, the efficacy of single or combination local antibiotics has not been studied. This retrospective study evaluated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Method. We studied patients with microbiologically confirmed osteomyelitis and fracture-related infection, who had implantation of antibiotic carriers as part of their surgical management. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. Results. There were 266 patients who met the inclusion criteria. Nine patients died before the outcome endpoint at 12 months and five patients were lost to follow up so were excluded. 252 patients were included in the final analysis and were well matched with regard to demographics, BACH score and microbiology. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. There was no difference for reoperation, ongoing suppressive antibiotic use, or clinical suspicion of infection. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95%CI 0.59-4.04, p=0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95%CI 1.13-10.76, p=0.03; Low BMI OR 0.91: 95%CI 0.84-0.99, p-0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p=0.434). Aminoglycoside resistance (confirmed and presumed) occurred in 39/113 (34.5%) of the aminoglycoside only group and 36/139 (25.9%) of the combination group (p=0.137). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95%CI 0.05-3.01, p=0.37). Conclusions. Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of osteomyelitis and FRI. Laboratory measured resistance, using currently accepted breakpoints, may not be relevant in local therapy

Aims. Infective complications following implant related orthopaedic surgery or fracture related infection are associated with high costs and increased length of stay (LOS). However, the economic burden of disease before, during and after definitive osteomyelitis surgery is not well quantified. The Hospital Episode Statistics (HES) database captures all admissions, outpatient appointments and emergency department attendances at NHS hospitals in England. We identified all patients with a diagnostic code of osteomyelitis and quantified the tariff costs associated with the surgical treatment of osteomyelitis. We also collected all recorded healthcare events related to osteomyelitis for two years preceding the initial osteomyelitis treatment procedure, as well as for two years after the procedure. We compared average osteomyelitis treatment costs in England against a dedicated specialist multidisciplinary bone infection centre. Methods. We interrogated the HES database for all patients given a diagnostic code of osteomyelitis (M86) between April 2013 and January 2017. We excluded all cases with a diagnosis of osteomyelitis and an index procedure of an amputation for diabetes or arterial disease. Of the remaining 104,622 patients there were 24,408 cases who had their index procedure for osteomyelitis in this time period. Of these we compared a subset of 575 cases treated in a specialist bone infection centre. Results. Index procedure costs were lower in specialist centres compared to national average (£4100.09 vs. 4835.59) equating to a potential saving of £4.67 million per year if all cases were treated in similar specialist centres. Average LOS for the index procedure was lower in the specialist centre (12.4 days) compared to the national average (17.3 days). Assuming a bed cost of £500 per day, treating all patients in similar specialist centres could save £15.95 million per year. The post procedure costs were lower for specialist centre patients compared to national average, equating to a potential saving of £7.42 million per year. The average post procedural LOS in the national cohort was 2.44 days longer than the specialist centre, equating to an additional 15,508 bed days per year. Conclusions. Although tariff costs do not reflect true costs this study demonstrates that osteomyelitis is a significant economic burden to the English health service. Treating infection in dedicated specialist multidisciplinary centres requires a lot of resources and costs a lot of money. However, treating infection outside this environment seems to cost more and results in longer inpatient stays and higher associated costs

Acute Haematogenous Osteomyelitis (AHO) remains a cause of severe illness among children with the possibility of long-term consequences for growth and development. Previous research on sequelae from AHO rarely considers outcomes more than two years following treatment. This study aims to establish the quality of life of patients diagnosed with AHO in childhood up to 13 years after diagnosis, evaluating the impact on social, emotional, physical, and school function. Children treated for AHO between 2008–2018 at a tertiary referral centre in New Zealand were identified. PedsQL™ questionnaires were conducted via phone with either the child or primary caregiver and responses analysed. 40 patients met inclusion criteria, were contactable by phone, and consented to participate. The mean age was 7 years (range 0–15) and most were female (60%). Health related quality of life (HRQOL) was scored as a percentage with most participants scoring >80% (n=27). Those who do experience reduced quality of life following treatment for AHO were likely to complain of pain, stiffness, or anxiety. The impact of significant childhood illness on mental health was not adequately captured by the PedsQL™ but was highlighted in qualitative feedback. We conclude that the majority of children treated for AHO reported excellent health-related quality of life up to 13 years following treatment although an negative impact on mental health was reported using qualitative analysis. A refined scoring system is needed to assess the long-term impact of musculoskeletal infection

Aim. Several local antibiotic-eluting drug delivery systems have been developed to treat bacterial bone infections. However, available systems have significant shortcomings, including suboptimal drug-release profiles with a burst followed by subtherapeutic release, which may lead to treatment failure and selection for drug resistance. Here, we present a novel injectable, biocompatible, in situ-forming depot, termed CarboCells, which can be fine-tuned for the desired antibiotic-release profile. The CarboCell technology has flexible injection properties that allow surgeons to accurately place antibiotic-eluting depots within and surrounding infectious sites in soft tissue and bones. The CarboCell technology is furthermore compatible with clinical image-guided injection technologies. These studies aimed to determine the therapeutic potential of CarboCell formulations for treatment of implant-associated osteomyelitis by mono- and dual antimicrobial therapy. Methods. The solubility and stability of several antibiotics were determined in various CarboCell formulations, and in vitro drug release was characterized. Lead candidates for antimicrobial therapy were selected using a modified semi-solid biofilm model with 4-day-matured Staphylococcus aureus biofilm (osteomyelitis-isolate, strain S54F9). Efficacy was investigated in a rat implant-associated osteomyelitis model established in the femoral bone by intraosseous implantation of a stainless-steel pin with 4-day-old in vitro-matured S. aureus biofilm. CarboCells were injected subcutaneously at the femur, and antimicrobial efficacy was evaluated 7 days post-implantation. Lead formulations were subsequently tested in a well-established translational implant-associated tibial S. aureus osteomyelitis pig model. Infection was established for 7 days before revision surgery consisting of debridement, washing, implantation of a new stainless-steel pin, and injection of antibiotic-releasing CarboCells into the debrided cavity and in the surrounding bone- and soft-tissue. Seven days post-revision, pigs were euthanized, and samples were collected for microbial and histopathological evaluation. Results. Lead antimicrobial agents were soluble in high concentrations and were stable in CarboCell formulations. Three combinations completely eradicated bacteria in the in vitro semi-solid biofilm model. In the rat osteomyelitis model, CarboCell formulations of the lead combinations also eradicated bacteria in bone and implant in several rats and significantly reduced infection in all treated rats. In the pig model, CarboCell antimicrobial monotherapy demonstrated promising therapeutic efficacy, including complete eradication of infection in bone and implants in several pigs and significantly reduced bacterial burden in others. Conclusions. Using the CarboCell technology for antimicrobial delivery exert substantial loco-regional efficacy. The attractive sustained high-dose antibiotic release profile combined with the flexible injection technology allows surgeons to accurately place effective drug-eluting depots in key areas not accessible to competing technologies