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Staphylococcus aureus (S. aureus)-induced bone loss is a significant challenge in the treatment of osteomyelitis. Our previous study was the first to confirm that granulocyte colony-stimulating factor (G-CSF) mediates S. aureus-induced bone loss. However, the underlying mechanism remains unknown. The objective of this study was to elucidate this. We found G-CSF mediated BMSC senescence and increased IL-1β concentration of serum and bone marrow in mice after S. aureus infection. Furthermore, we demonstrated that G-CSF promoted the expression of IL1b in murine bone marrow-derived neutrophils. Notably, we identified that IL-1β mediated BMSC (bone marrow mesenchymal stromal cell) senescence in mice after S. aureus infection. Importantly, IL-1β neutralizing antibody effectively alleviated BMSC senescence and bone loss caused by S. aureus infection in mice. In terms of molecular mechanism, we found IL-1β induced BMSC senescence by JNK/P53 and JNK/BCL2 pathways. Collectively, G-CSF promotes IL-1β production which induces BMSC senescence via JNK/P53 and JNK/BCL2 pathways, leading to S. aureus-induced bone loss. This study identified novel targets for preventing and treating S. aureus-induced bone loss in osteomyelitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro . When evaluated in vivo in the Staphylococcus aureus -induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

Osteomyelitis (OM) is an inflammatory disease of bone infection and destruction characterized by dysregulation of bone homeostasis. Staphylococcus aureus (SA) has been reported to be the most common pathogen causing infectious OM. Recent studies have demonstrated that N6-methyladenosine (m6A) regulators are associated with the development of OM. However, the molecular mechanism of m6A modifications in OM remains unclear. Here, we investigated the function of methyltransferase-like 3 (METTL3)-mediated m6A modification in OM development. In this study, human bone mesenchymal stem cells (hBMSCs) were treated with staphylococcal protein A (SpA), a vital virulence factor of SA, to construct cell models of OM. Firstly, we found that METTL3 was upregulated in OM patients and SpA-induced hBMSCs, and SpA treatment suppressed osteogenic differentiation and induced oxidative stress and inflammatory injury in hBMSCs. Functional experiments showed that METTL3 knockdown alleviated the inhibition of osteogenic differentiation and the promotion of oxidative stress and inflammation in SpA-treated hBMSCs. Furthermore, METTL3-mediated m6A modification upregulated miR-320a expression by promoting pri-miR-320a maturation, and the mitigating effects of METTL3 knockdown on SpA-mediated osteogenic differentiation, oxidative stress and inflammatory responses can be reversed by miR-320 mimic. In addition, we demonstrated that phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) was a downstream target of miR-320a, upregulation of PIK3CA alleviated miR-320a-induced inhibition of osteogenic differentiation, and upregulation of oxidative stress and inflammatory responses during SpA infection. Finally, we found that silencing METTL3 alleviated OM development by regulating the miR-320a/PIK3CA axis. Taken together, our data demonstrated that the METTL3/m6A/miR-320a/PIK3CA axis regulated SpA-mediated osteogenic differentiation, oxidative stress, and inflammatory responses in OM, which may provide a new therapeutic strategy for OM patients., (© 2024. The Author(s).)

Background: With the application of PCR testing and Metagenomic Next-Generation Sequencing(mNGS), the detection rate of causative organisms in paediatric bone and joint infections has been greatly improved. The aim of our study is to identify some indicators that could be used to distinguish the culture results to optimize the use of PCR and mNGS., Methods: In this study, a total of 117 cases of acute osteomyelitis of long bones in children who underwent pus culture were included. Patients were grouped as culture-negative (n:21) and culture-positive (n:96) groups according to the results of pus culture. Age, sex, duration of onset, maximum body temperature at onset, inflammatory indicators and D-dimer after admission were systematically collected for all patients and were compared for both groups. ROC curve (ROC) was used to evaluate the diagnostic efficiency of culture-negative. Logistic regression analysis was conducted to determine independent risk factors for culture-negative., Results: There was no significant difference in age, sex and erythrocyte sedimentation rate between culture-negative group and culture-positive group (P > 0.05). The duration of onset was longer, and the temperature, white blood cells, neutrophils count, C-reactive protein and D-dimer were less elevated in culture-negative acute osteomyelitis (P < 0.05). Duration of onset, maximum body temperature at onset, white blood cell count, neutrophil count, C-reactive protein, and D-dimer have certain diagnostic efficacy in judging the efficacy of negative culture. Logistic regression analysis indicated that the duration of onset more than 6.5 days, the maximum body temperature at onset lower than 38.35℃ and C-reactive protein lower than 78.40 mg/L were independent risk factors for negative culture (P < 0.05)., Conclusions: Our study revealed that duration of onset more than 6.5 days, maximum body temperature at onset lower than 38.35℃ and C-reactive protein lower than 78.40 mg/L were independent risk factors for predicting negative culture. In children with this type of acute osteomyelitis, we recommend that the pus be tested by PCR or mNGS as a priority., (© 2024. The Author(s).)

Mycetoma of the hand is a chronic granulomatous disease seen in the tropics and subtropical regions, mainly affecting the skin and subcutaneous tissue of the foot. Primary actinomycotic osteomyelitis involving the metacarpals is rarely reported in the literature. The conventional treatment for actinomycosis has been high-dose penicillin. We report a case of chronic osteomyelitis in the metacarpals of the hand caused by actinomycetes in a woman in her 40s. She underwent surgical intervention in the form of wound debridement and curettage, followed by a 6-month course of Welsh regimen after a biopsy confirmed the diagnosis of actinomycotic osteomyelitis. This case report underscores the importance of recognising primary actinomycosis as a potential cause of chronic osteomyelitis at unusual sites and highlights the efficacy of combined surgical debridement, biopsy and adequate antibiotic management in consultation with infectious disease specialists in achieving good outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The present minireview aims to provide a context for imagination of the timespan for bone infection evolution from the origin of cellular bone tissue to modern orthopedic surgery. From a phylogenetic osteomyelitis-bracketing perspective, and due to the time of osteocyte origin, bacteria might have been able to infect the skeleton for approximately 400 million years. Thereby, bone infections happened simultaneously with central expansions of the immune system and development of terrestrial bone structure. This co-evolution might aid in explaining the many immune evasion strategies seen in the field of bone infections. Bone infection patients with long disease-free periods followed by sudden recurrence and anamnesis of long-term and low-grade infections indicate that bacteria can perform silent parasitism within bone tissue (parasitism; one organism lives on another organism, the host, causing it harm and is structurally adapted to it). The silence seems to be disturbed by immunosuppression and the present minireview shows that a compromised immune system has been associated with bone infection development across all species in the phylogenetic tree. Orthopedic surgery, including arthroplasty and osteosynthesis, favor introduction of bacteria and prosthesis/implant related infections are thus anthropogenic infections (anthropogenic; resulting from the influence of human beings on nature). In that light it is important to remember that the skeleton and immune system have not evolved for millions of years to protect titanium alloys and other metals, commonly used for orthopedic devices from bacterial invasion. Therefore, these relatively new orthopedic infection types must be seen as distinct with unique implant/prosthesis related pathophysiology and immunology., Competing Interests: Declaration of competing interest No conflict of interest by any of the authors, (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In surgery for sepsis it is a well-established principle that no internal osteosynthetic material should be implanted in cases of chronic osteomyelitis. Therefore, the surgical treatment with intramedullary nails is so far used only rarely in cases of chronic osteomyelitis., Objective: This study analyzed whether the implantation of tibial intramedullary nails is an effective treatment for chronic osteomyelitis and how high is the rate of reinfection., Material and Methods: A retrospective analysis of patients with an infected pseudarthrosis of the tibia in whom a gentamycin-coated nail (ETN) or an uncoated tibial intramedullary nail (UCN) was implanted between December 2011 and December 2019 was carried out. The preoperative, perioperative and postoperative results were evaluated., Results: During the study period 29 patients received a UCN and 27 patients received an ETN. Of the patients 95% (n = 53) had been previously unsuccessfully treated with external fixation. Postoperative complications occurred in 45% of the patients and more often in the ETN group (48% vs. 41%). Reexacerbation of the infection occurred in 20 patients and more frequently in the UCN group (38% vs. 33%). The nonunion already showed a bony consolidation at the time of the exacerbation in 10 patients (50%). At the end of the follow-up a consolidation was present in 48 patients (86%), more frequently in the UCN group (90% vs. 78%). Of the patients 50 (89%) reached full weight bearing without any differences between the groups., Conclusion: Despite a relatively high a rate of postoperative complications the risk of reinfection was acceptable with good functional and radiological results. The main general advantages of nailing are without doubt the high primary stability, the implantation with preservation of the soft tissue and the improved wearing comfort for patients., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture-based methods are often time-consuming and prone to false-negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real-time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2-22 h (median 4.85, range 1.28-21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74-100%), sensitivity (100%), and specificity (65-100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics., (© 2024 The Author(s). APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions. We have isolated a pair of S. aureus isolates from an individual patient with osteomyelitis presenting with heterogenous phenotypes; a stable SCV (sSCV) and a SCV that reverts upon laboratory culturing to the usual, active and non-SCV cell type. Thus we are able use this pair to investigate and compare the genetic mechanisms that underlie the clinical variatons of SCV phenotype. The switch to the sSCV phenotype was associated with frameshift mutations in the enolase eno and the histidine kinase arlS. The phenoptye of the sSCV was an impeded growth dependent on amino acid catabolism and modulated biofilm. These mutations present potentially a new molecular mechanism which confer persistence within osteomyelitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cutibacterium acnes, part of normal skin flora, is increasingly recognized as an opportunistic pathogen capable of causing chronic prosthetic joint infections (PJI) associated with total hip and knee arthroplasty. However, there is a paucity of literature examining the pathogenesis of C. acnes during PJI. To study this, we developed an implant-associated osteomyelitis murine model in which 8-10-week-old C57BL6 mice were subjected to transtibial implantation of titanium or stainless-steel L-shaped pins contaminated with C. acnes. Postsurgery, mice were killed on Days 14 and 28 for terminal assessments of (1) bacterial load in bone, implant, and internal organs (heart, spleen, kidney, and liver), (2) bone osteolysis (micro-CT), (3) abscess formation (histology), and (4) systematic electron microscopy (EM). In vitro scanning EM (SEM) confirmed that C. acnes can form biofilms on stainless-steel and titanium implants. In mice, C. acnes could persist for 28 days in the tibia. Also, we observed C. acnes dissemination to internal organs. C. acnes chronic osteomyelitis revealed markedly reduced bone osteolysis and abscess formation compared to Staphylococcus aureus infections. Importantly, transmission EM (TEM) investigation revealed the presence of C. acnes within canaliculi, demonstrating that C. acnes can invade the osteocyte lacuno-canalicular networks (OLCN) within bone. Our preliminary pilot study, for the first time, revealed that the OLCN in bone can be a reservoir for C. acnes and potentially provides a novel mechanism of why C. acnes chronic implant-associated bone infections are difficult to treat., (© 2024 Orthopaedic Research Society.)

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (β-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and β-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang., Methods: A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification., Results: Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41-50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA., Conclusion: Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment., (© 2024. The Author(s).)

Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases., (© 2024. The Author(s).)

Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are tools that can be employed to interrogate the lipidome of S. aureus-infected murine femurs and reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, suggesting a hypothesized dysregulation of lipid metabolism in a population of cells that cannot be discerned with traditional microscopy. These data provide insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aims to identify risk factors associated with Methicillin-resistant Staphylococcus aureus (MRSA) infection in children diagnosed with acute osteomyelitis (AO) and to elucidate the laboratory characteristics of these MRSA-infected children to enhance early targeted therapeutic interventions., Methods: We conducted a retrospective analysis involving 123 children with acute osteomyelitis treated at our hospital. Upon admission, we measured white blood cell (WBC) counts, C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), and platelet counts. Patients were categorized into two groups: the non-MRSA group (n = 73) and the MRSA group (n = 50), with values assigned as follows (non-MRSA group = 0, MRSA group = 1)., Results: The MRSA group had a significantly higher average age compared to the non-MRSA group (P < 0.05). Notably, the incidence of suppurative arthritis was significantly lower in the MRSA group (P < 0.05). At the time of admission, CRP levels in the MRSA group were markedly elevated compared to those in the non-MRSA group (P < 0.01). After three days of empirical therapy, both WBC and CRP levels remained significantly higher in the MRSA group compared to the non-MRSA group (P < 0.05)., Conclusions: In children newly admitted with acute osteomyelitis, a CRP level exceeding 73.23 µg/mL may indicate a high likelihood of MRSA infection. For children with AO who have been hospitalized for three days on empirical therapy, the presence of WBC > 10.95 × 10^9/L, CRP > 49.56 µg/mL, age > 3.5 years, and the absence of suppurative arthritis suggests a heightened risk of MRSA infection., (© 2024. The Author(s).)

Background: Congenital syphilis (CS) is a sexually transmitted disease caused by Treponema pallidum (TP). When the skeletal system is involved, it often results in multiple, symmetrical bone destruction at the epiphyses of long tubular bones such as the humerus and radius, rarely involving the calcaneus. This article reports a case of calcaneal osteomyelitis caused by TP in a child with no other bone damage and subtle clinical manifestations, No similar cases have been reported., Case Presentation: A 4-month-old male infant presented with right foot swelling without any obvious cause and no history of trauma. X-ray and CT scans showed bone loss in the calcaneus and surrounding soft tissue swelling. Review of past medical records revealed that the infant had been diagnosed with CS infection during a hospital stay for "pneumonia" at one month old. The parents refused surgery, opting for conservative treatment at an external hospital for three weeks, during which the symptoms of the affected foot showed no significant improvement. Subsequently, the child was treated at our hospital with surgery, including lesion removal and cast fixation, followed by oral antibiotic treatment. The last follow-up showed no swelling or tenderness in the affected foot, with good mobility, and X-rays indicated that the bone had essentially returned to normal., Conclusions: Early CS rarely involves the calcaneus. When diagnosing unexplained calcaneal osteomyelitis in infants, this rare cause should be considered. A thorough medical history should be taken and a careful physical examination conducted. Once diagnosed, timely surgical debridement and appropriate antibiotic therapy targeting TP infection are required. Early identification and intervention can result in a good prognosis without related complications., (© 2024. The Author(s).)

The therapeutic challenges of orthopedic device-related infections and emerging antimicrobial resistance have attracted attention to drug delivery technologies. This study evaluates the preclinical efficacy of local single- and dual-antibiotic therapy against implant-associated osteomyelitis (IAO) using a drug-eluting depot technology, CarboCell, that provides sustained release of high-dose antibiotics and allows for strategic in situ placement in relation to infectious lesions. Clindamycin and gentamicin were formulated in CarboCell compositions. One-stage-revision of tibial Staphylococcus aureus IAO was conducted in 19 pigs. Pigs were treated locally with CarboCell containing either gentamicin alone for 1 week or a co-formulation of gentamicin and clindamycin for 1 or 3 weeks. Bone, soft tissue, and antibiotic depots were collected for microbiology, histology, and HPLC analyses. Supporting in vivo release studies of CarboCell formulations were performed on mice. Both single- and dual-antibiotic CarboCell formulations were developed and capable of eradicating the infectious bacteria in bone and preventing colonization of implants inserted at revision. Eradication in soft tissue was observed in all pigs after 3 weeks and in 6/9 pigs after 1 week of treatment. Neutrophil counts in bone tissue were below the infection cut-off in all pigs receiving the dual-antibiotic therapies, but above in all pigs receiving the single-antibiotic therapy. Histological signs of active bone reorganization and healing were observed at 3 weeks. In conclusion, all CarboCell formulations demonstrated strong therapeutic activity against IAO, eradicating S. aureus in bone tissue and preventing colonization of implants even without the addition of systemic antibiotic therapy., Competing Interests: A.E.H., J.R.H., and T.L.A. are co-inventors on patents covering the CarboCell technology. All other authors declare no conflict of interest.

Osteomyelitis caused by Staphylococcus aureus can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte S. aureus infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 S. aureus strains, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone estimated achievable concentration was commonly above their respective MIC for the strains tested were further assayed in a human osteocyte infection model under acute and chronic conditions. Osteocyte-like cells were treated at 1×, 4×, and 10× the MIC for 1 and 7 days following infection (acute model), or at 15 and 21 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of CFU reduction, small colony variant formation, and bacterial mRNA expression change. Only rifampicin, levofloxacin, and linezolid reduced intracellular CFU numbers significantly in the acute model. Consistent with the transition to a non-culturable state, few if any CFU could be recovered from the chronic model. However, no treatment in either model reduced the quantity of bacterial mRNA or prevented non-culturable bacteria from returning to a culturable state. These findings indicate that S. aureus adapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state that is protected against antibiotics, even at 10× their MIC. Thus, new therapeutic approaches are necessary to cure S. aureus intracellular infections in osteomyelitis., Competing Interests: The authors declare no conflict of interest.

Musculoskeletal infection of pelvis can be confused with septic arthritis of the hip, irritable hip, sacroiliitis, and spondylodiscitis in the initial period. This study aimed to present the complete clinical picture of pelvic infective osteomyelitis (PIO) in children along with its natural course. Two researchers independently used PubMed and Scopus electronic databases for the literature review. This review includes all studies reporting PIO in the pediatric age group. The final inclusion of 11 eligible studies was done. A total of 277 patients were analyzed from the included studies with the majority of males (158/242, 65.2%). Hip and groin pain (147/195, 75.3%) and limp (155/249, 62.2%) were the common presenting symptoms. Increased systemic temperature (83/103, 80.5%) and localized tenderness at the hip joint area (90/121, 74.3%) were among the commonest signs. Magnetic resonance imaging was an investigation of choice for diagnosis (89/93, 95.6%). Blood culture showed growth in 47.6% (119/250) patients with Staphylococcus aureus (83/102, 81.3%) being the most common isolated organism. Treatment with sensitive antibiotics was the mainstay of management with surgery for debridement or biopsy being required in only 16.1% (23/142) of the patients. PIO in children is a rare condition mimicking several other disease processes affecting the neighboring tissues the diagnosis of which gets limited in low-resource settings. Further prospective clinical studies are the need of the hour to validate the guideline proposed. Explorative studies to define a clinical scoring system to differentiate septic arthritis of the hip from PIO may be considered., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Brodie's abscess is a subacute or chronic osteomyelitis characterised by an intraosseous abscess. It may present months to years after the inciting event. Staphylococcus aureus is the most common causative organism of Brodie's abscess, while Gram-negative bacteria are uncommon causative organisms. A combination of culture-directed antibiotics and surgical debridement is key to successful management. This case report describes a patient with a history of minor trauma preceding the development of Brodie's abscess of the calcaneus caused by Serratia marcescens This was managed successfully with surgical debridement, followed by oral antibiotics., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Tropicoporus tropicalis (formerly Phellinus tropicalis) is a saprophytic basidiomycete that has been implicated in refractory mycoses in humans, particularly in patients with chronic granulomatous disease. Despite its clinical significance, T. tropicalis is an under-recognised cause of eumycetoma, with no prior reports available. We present a case of white grain eumycetoma with associated osteomyelitis of the left foot, caused by T. tropicalis, confirmed through 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient was treated with itraconazole 200 mg daily, leading to gradual improvement. A review of the literature on T. tropicalis infections in humans reveals its characteristic manifestations, which include osteomyelitis, soft tissue abscesses, pulmonary nodules and keratitis. These infections are locally destructive but have the potential to disseminate. Diagnosis is often delayed and relies on molecular techniques. Amphotericin B combined with an azole appears to be the most effective treatment, often necessitating concurrent surgical drainage. In conclusion, T. tropicalis is a newly recognised pathogen associated with eumycetoma and poses an increased risk of osteomyelitis. Molecular identification, such as sequencing the internal transcribed spacer (ITS) region from cultures or tissue specimens, is crucial for accurate identification of this pathogen., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objectives: To identify the risk factors and clinical manifestations associated with skull base osteomyelitis., Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from July 2013 to October 2020 related to adult patients of either who presented with base osteomyelitis. All relevant data was retrieved from hospital records. Data was analysed using SPSS 16., Results: Of the 56 patients with a mean age of 58.12±17.79 years, 39 (69.6%) were males. Diabetes was the most common comorbidity (n 39, 69.6%). The majority of patients had chronic sinusitis (n 34,60.7%) otitis media (n 20, 35.7%) or head and neck surgery (n 18, 32.1%) within the preceding 2 years. The mean duration between onset of symptoms and presentation to healthcare facility was 12±13.96 weeks. The most common presenting symptom was headache (n 38, 68%). The majority of patients (n 34 ,59.6 %) had fungal organisms isolated from tissue culture. Cranial nerve palsies were present in 44 (77%) patients. Out of 56 patients, 22(39.2%) were lost to follow and overall mortality was high (n 11, 19.6%). Sepsis was found to be associated with increased mortality (p=0.008)., Conclusions: Skull base osteomyelitis was associated with significant morbidity and mortality, and posed significant diagnostic and therapeutic challenges.

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

This article focuses on the advancements made in diagnostic techniques and drug interventions of acute hematogenous osteomyelitis. A diagnosis necessitates a combination of factors, including inflammatory markers and imaging findings, as well as the collection of specimens for culture when feasible. Subsequently, treatment should be based on epidemiology, mechanisms of resistance, and susceptibility findings. A brief course of intravenous (IV) antibiotics, followed by oral antibiotics, may be employed for uncomplicated infections if there is improvement in the clinical condition and a decline in C-reactive protein levels. However, for complex infections caused by methicillin-resistant Staphylococcus aureus, prolonged administration of IV antibiotics is recommended, along with surgical intervention if necessary. [ Pediatr Ann . 2024;53(10):e392-e395.] .

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Xanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported., Case Presentation: We present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed., Conclusions: Although rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases., (© 2024. The Author(s).)

We discuss an illustrative case of Escherichia coli infected scalp abscess with osteomyelitis following a cephalhaematoma in a 19-day-old neonate. Cephalhaematoma is a common occurrence in neonates after prolonged labour, instrument-assisted, and traumatic deliveries and resolves spontaneously in the majority of cases. Infection may follow haematogenous dissemination or direct inoculation via a skin breach. Complications such as scalp abscess, sepsis, and osteomyelitis of the skull present with local signs, including increasing size, local erythema and tenderness, and fluctuant swelling., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Sickle cell disease (SCD) is a genetic disorder with a high infectious morbidity and mortality and a heterogeneous distribution in France. One of the challenges is to differentiate a bone and joint infection (BJI) from a vaso-occlusive crisis. This challenge is particularly prevalent in French Guiana, an overseas territory with the highest incidence of SCD in France. The aim of this study was to describe the epidemiology of BJI in children with SCD in French Guiana., Method: This was a retrospective multicentric descriptive study of SCD patients living in French Guiana aged under 18 and diagnosed with a BJI between 2010 and 2022. These BJI were divided into 2 groups: those with microbiological documentation (d-BJI) and those without microbiological identification (ud-BJI)., Results: A total of 53 episodes of BJI in 42 patients (mean age 7.2 years) were reported. Clinical symptoms on arrival were comparable between the d-BJI and ud-BJI groups. Patients in the d-BJI group had longer average hospital stays (40.4 days vs. 16.8 days, P = 0.01) and Salmonella spp. were the most identified bacteria (n = 8/13). White blood cell count was greater in the d-BJI group (30.3 G/L vs. 18.G/L, P = 0.01) and a collection was more frequently identified on imaging (11/13 vs. 16/40, P = 0.01) in this group. Initial in-hospital antibiotic therapy was longer in the d-BJI group (17.2 days vs. 12.8, P = 0.02), as were infection-related complications (9/13 vs. 12/40 P = 0.01)., Conclusion: BJI in children with SCD is not sufficiently microbiologically documented. Progress must be made to improve the documentation of BJI., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Bacterial osteomyelitis, an inflammatory response in the bone caused by microorganisms, typically affects the metaphysis in the skeletally immature. Bacterial osteomyelitis possesses a significant diagnostic challenge in pediatric patients due to its nonspecific clinical presentation. Because the metaphysis is the primary focus of infection in skeletally immature patients, understanding the normal physiologic, maturation process of bones throughout childhood allows to understand the pathophysiology of osteomyelitis. Timely and accurate diagnosis is crucial to initiate appropriate treatment, and prevent long-term sequelae and efforts must be made to isolate the causative organism. The potential causative organism changes according to the age of the patient and underlying medical conditions. Staphylococcus Aureus is the most common isolated bacteria in pediatric pyogenic osteomyelitis whereas Kingella Kingae is the most common causative agent in children aged 6 months to 4 years. Imaging plays a pivotal role in the diagnosis, characterization, evaluation of complications, and follow up of bacterial osteomyelitis. Imaging also plays a pivotal role in the evaluation of potential neoplastic and non-neoplastic mimickers of osteomyelitis. In children, MRI is currently the gold standard imaging modality when suspecting bacterial osteomyelitis, whereas surgical intervention may be required in order to isolate the microorganism, treat complications, and exclude mimickers., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are bone resorbing cells that are often increased in bone infected with S. aureus. The cytokine RANKL is essential for osteoclast formation under physiological conditions but in vitro evidence suggests that inflammatory cytokines may by-pass the requirement for RANKL. The goal of this study was to determine whether RANKL-dependent osteoclast formation is essential for the bone loss that occurs in a murine model of S. aureus osteomyelitis. To this end, humanized-RANKL mice were infected by direct inoculation of S. aureus into a unicortical defect in the femur. Mice were treated with vehicle or denosumab, a human monoclonal antibody that inhibits RANKL, both before and during a 14-day infection period. The severe cortical bone destruction caused by infection was completely prevented by denosumab administration even though the bacterial burden in the femur was not affected. Osteoclasts were abundant near the inoculation site in vehicle-treated mice but absent in denosumab-treated mice. In situ hybridization demonstrated that S. aureus infection potently stimulated RANKL expression in bone marrow stromal cells. The extensive reactive bone formation that occurs in this osteomyelitis model was also reduced by denosumab administration. Lastly, there was a notable lack of osteoblasts near the infection site suggesting that the normal coupling of bone formation to bone resorption was disrupted by S. aureus infection. These results demonstrate that RANKL-mediated osteoclast formation is required for the bone loss that occurs in S. aureus infection and suggest that disruption of the coupling of bone formation to bone resorption may also contribute to bone loss in this condition., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Published by Elsevier Inc.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics., Methods: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSA; n = 6) or osteomyelitis (OM-MRSA; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and 6 OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS)., Results: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin, and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates., Conclusions: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Bone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics., Methods: CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology., Results: CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs., Conclusions: Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care., Competing Interests: Potential conflicts of interest. A. E. H., J. R. H., and T. L. A. are coinventors on patents covering the CarboCell technology. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Calcaneal osteomyelitis (CO) poses a formidable challenge in treatment due to the distinct anatomical structure and functional properties of the calcaneus. The present study endeavors to furnish a thorough and comprehensive understanding of the clinical manifestations, therapeutic strategies, and therapeutic outcomes pertaining to pediatric calcaneal osteomyelitis (PCO) by conducting a meticulous synthesis and analysis of cases reported in the literature., Methods: A systematic search of the PubMed, Embase, and Cochrane Library databases was conducted to identify English-language studies analyzing PCO between 2000 and 2021. The quality of the included studies was assessed using the National Institutes of Health (NIH) assessment scale. Effective data were extracted and analyzed., Results: A total of 42 studies, encompassing 128 patients, fulfilled the established inclusion criteria. The gender distribution revealed a male-to-female ratio of 2:1 (81 boys and 40 girls). The median age at the time of diagnosis was 8 years, while the median duration of symptoms was 0.6 month. Trauma emerged as the primary etiology (41 cases, 54%), and limited activity was the most prevalent symptom (68 cases). The positive rate for pathogen culture was 75.4% (49/65), with Staphylococcus aureus being the most commonly isolated pathogen (28 cases, 57.1%). Surgical intervention was performed in 51% (64/126) of the patients, with debridement serving as the primary surgical strategy. The rate of infection recurrence was 6.8% (8/118), and the risk of below-knee amputation was 0.8% (1/124)., Conclusions: PCO occurred more frequently in male patients, with trauma being the primary underlying cause and Staphylococcus aureus being the most prevalent bacterial pathogen isolated. Over half of the patients underwent surgical intervention. Nonetheless, it is imperative that treatment strategies undergo further refinement, as approximately 7% of patients experienced infection recurrence., (© 2024. The Author(s).)

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis . She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.

The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = <0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p < 0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Although little is known about the regulatory mechanisms underlying the pathogenesis of osteomyelitis caused by Staphylococcus aureus (S. aureus), hypoxia-inducible factor-1α (HIF-1α) and STIP1 homology and U-box containing protein 1 (STUB1) have been found to be up-regulated in both S. aureus infected MC3T3-E1 cells and in patients with osteomyelitis. HIF-1α directly targets STUB1 to induce its expression. In MC3T3-E1 cells infected with S. aureus, silencing HIF-1α and STUB1 and administering the hypoxia inhibitor IDF-11774 consistently increased the expression of OSX and RUNX2, as well as the levels of alizarin Red S and alkaline phosphatase activity. In a mouse model of osteomyelitis, S. aureus infection elevated HIF-1α expression and serum STUB1 levels. Interleukin (IL)-6, IL-1β, and C-reactive protein levels in serum were reduced after treatment with the hypoxia inhibitor IDF-11774. Following an infection with S. aureus, hypoxia was activated to cause STUB1 overexpression by directly targeting HIF-1α, ultimately causing osteomyelitis symptoms such as osteogenesis and mineralization defected and increased inflammation. This study presents a novel signaling cascade in the pathogenesis of osteomyelitis involving hypoxia/HIF-1α/STUB1. This signaling cascade may be a target for therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Introduction: Study aimed to ole of surgery along with antimicrobials to improve clinical outcomes in treating refractory cases of skull base osteomyelitis (SBO)., Methods: A prospective observational study in a tertiary care centre with 70 SBO patients meeting eligibility criteria. The study population comprised 35 patients refractory to systemic antimicrobials of at least 4 weeks duration who later underwent surgery in addition to medication (surgical group). They were compared with a medical group that responded to medications alone. The outcome variables studied were the resolution of clinical features (pain, discharge, radiology, and inflammatory markers), culture yield, and total duration of treatment., Results: According to our study, relief of pain was faster in the surgical group (1.66 against 4.57 months) with statistical significance (p < 0.001). Relief of symptoms (p < 0.001), radiological improvement (p = 0.001), and normalising of inflammatory markers (p < 0.001) were better in the surgical group than in the medical group. The duration of treatment was an average of 9.2 months in the surgical group compared to 11.3 months in the medical group (p = 0.019). Microbial culture from deep tissue sampling was positive in 24 surgical patients (68.57%)., Conclusions: The treatment response in selected patients of refractory SBO who underwent surgery along with antimicrobials was better than the group who responded to antimicrobials alone. Surgery provided higher microbial yield resulting in culture-specific antimicrobials. The surgical group observed faster relief of symptoms, reduced hospital stay, and total treatment duration., (© 2024 John Wiley & Sons Ltd.)

Osteomyelitis, a grave deep tissue infection primarily caused by Staphylococcus aureus, results in serious complications such as abscesses and sepsis. With the incidence from open fractures exceeding 30 % and prevalent antibiotic resistance due to extensive treatment regimens, there's an urgent need for innovative, antibiotic-free strategies. Photothermal therapy (PTT) and photodynamic therapy (PDT) renowned for generating localized reactive oxygen species (ROS), face limitations in penetration depth. To overcome this, our method combines the deep penetration attributes of medical microwaves (MW) with the synergistic effects of the ZnO/ZrO 2 solid solution. Comprehensive in vitro and in vivo evaluations showcased the solid-solution's potent antibacterial efficacy and biocompatibility. The ZnO/ZrO 2 solid solution, especially in a 7:3 M ratio, manifests superior microstructural characteristics, optimizing MW-assisted therapy. Our findings highlight the potential of this integrated strategy as a promising avenue in osteomyelitis management., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature., Case Presentation: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved., Results: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died., Conclusions: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Manoj Kumar Panigrahi, Shakti Kumar Bal, Tara Prasad Tripathy, Akshaya Moorthy, Swadesh Kumar Mohanty, Ashoka Mahapatra, Sourin Bhuniya.)

Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Ancuța et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Case: A 38-year-old woman presented to our clinic with right knee pain and difficulty ambulating. After cultures were obtained, a cryptococcal infection of the patella was identified. Subsequent workup revealed previously undiagnosed HIV/AIDS and a disseminated cryptococcal infection., Conclusion: Over a 20-month course, the patient was treated with fluconazole and antiretroviral therapy with very limited medication compliance. The disseminated infection caused cutaneous, hepatic, and cerebral complications. Eventually, compliance improved, and a final procedure to obtain post-treatment cultures and apply antifungal bone matrix was completed. The patient cleared the infection and will likely require lifetime antifungal treatment., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C424)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Brucella disease is an infectious disease caused by Brucella bacteria. It is transmitted through the consumption of unpasteurized dairy products and undercooked meat and penetration through the skin of individuals in contact with farm animals. A detailed medical history is of utmost importance in the diagnosis. Headache, cyclical fever, sweating, vomiting, abdominal pain, and wandering arthralgia are among the main clinical symptoms. Brucella infection is usually characterized by inflammation in the musculoskeletal system, and osteomyelitis is rarely seen. In this article, we report a case of osteomyelitis after neglected brucellosis.

Rezafungin is an echinocandin characterized by a long elimination half-life which allows for weekly administration. It has been recently approved for the treatment of candidemia. Few data are available about the long-term use of rezafungin and its use for deep infections like endocarditis and osteomyelitis. We describe our experience with its prolonged use in two azole-resistant Candida infections: a case of sacral osteomyelitis and a prosthetic valve endocarditis also involving a thoracic endovascular aneurysm repair., Competing Interests: The authors declare no conflict of interest.

Diabetic foot infection imposes a significant burden and is the major cause of nontraumatic limb amputation. Adequate patient management with effective antibiotic therapy is crucial.This retrospective cohort study aimed to characterize the microbiology and resistance patterns of moderate to severe neuropathic diabetic foot infection in patients hospitalized at a tertiary referral hospital between January 2020 and June 2023. Deep tissue specimens from ulcers were collected for culture.Sixty inpatients were included (62% male, mean age 59.1 ± 11.5 years). Osteomyelitis was present in 90% of the patients. Among 102 microorganisms (average of 1.91 ± 1.25 pathogens per patient), 60.8% were gram-positive bacteria, 31.4% were gram-negative, 3.92% were anaerobic bacteria, and 3.92% were fungi. Staphylococcus aureus (19%) and Enterococcus faecium (17%) were the most common. Pseudomonas aeruginosa (8%) and bacteria of the Enterobacterales family (24%) accounted for all the isolated gram-negative bacteria. Sixteen percent of Staphylococcus aureus and 67% of coagulase-negative Staphylococci were resistant to methicillin. Resistance to ampicillin was found in 11% of Enterococci. All Pseudomonas aeruginosa isolates were sensitive to piperacillin-tazobactam, ceftazidime, or cefepime. Among the Enterobacterales, resistance rates were 35% for piperacillin-tazobactam, 38% for ceftazidime, 21% for cefepime, and 13% for carbapenems.Although the prevalence of methicillin-resistant staphylococci was lower than that in other studies, carbapenem resistance among gram-negative bacteria warrants attention. This study highlights the importance of understanding local epidemiology for effective diabetic foot infection management and resistance mitigation., (© 2024. The Author(s).)

The ability of Staphylococcus aureus (S. aureus) to survive within macrophages is a critical strategy for immune evasion, contributing to the pathogenesis and progression of osteomyelitis. However, the underlying mechanisms remain poorly characterized. This study discovered that inhibiting the MEK1/2 pathway reduced bacterial load and mitigated bone destruction in a mouse model of S. aureus osteomyelitis. Histological staining revealed increased phosphorylated MEK1/2 levels in bone marrow macrophages surrounding abscess in the mouse model of S. aureus osteomyelitis. Activation of MEK1/2 pathway and its roles in impairing macrophage bactericidal function were confirmed in primary mouse bone marrow-derived macrophages (BMDMs). Transcriptome analysis and in vitro experiments demonstrated that S. aureus activates the MEK1/2 pathway through EGFR signaling. Moreover, we found that excessive activation of EGFR-MEK1/2 cascade downregulates mitochondrial reactive oxygen species (mtROS) levels by suppressing Chek2 expression, thereby impairing macrophage bactericidal function. Furthermore, pharmacological inhibition of EGFR signaling prevented upregulation of phosphorylated MEK1/2 and restored Chek2 expression in macrophages, significantly enhancing S. aureus clearance and improving bone microstructure in vivo. These findings highlight the critical role of the EGFR-MEK1/2 cascade in host immune defense against S. aureus, suggesting that S. aureus may reduce mtROS levels by overactivating the EGFR-MEK1/2 cascade, thereby suppressing macrophage bactericidal function. Therefore, combining EGFR-MEK1/2 pathway blockade with antibiotics could represent an effective therapeutic approach for the treatment of S. aureus osteomyelitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study aimed to analyze the distribution of pathogens and antimicrobial resistance in bone and joint infections (BJIs) among children under four years old., Methods: A retrospective analysis was conducted on the clinical data of children under four years old who received inpatient treatment for BJIs at the Children's Hospital of Soochow University between January 2016 and December 2022. Results of bacterial culture and antimicrobial resistance were analyzed., Results: Among the 131 patients, 52 (39.7%) showed positive bacterial culture results. There were Gram-positive (G+) bacteria detected in 38 strains (73.07%), Gram-negative (G-) bacteria in 12 strains (23.08%), and fungi in 2 strains (3.85%). Thirty-one strains of Staphylococcus aureus (S. aureus) were detected (59.62%), including 7 MRSA strains (22.58%). The resistance rate of G+ bacteria to penicillin was 72.97%, while resistance to erythromycin and clindamycin was approximately 50%. No resistance was found against linezolid, vancomycin, and teicoplanin. G- bacteria showed a sensitivity of 100% to carbapenems, including meropenem, ertapenem, and imipenem, a resistance rate of 91.67% to ampicillin-sulbactam, and relatively high resistance rates to compound sulfamethoxazole, ampicillin/sulbactam, and piperacillin., Conclusions: Regional variations existed in the distribution of pathogens and antimicrobial resistance in children under four years old with BJIs. In our hospital, the most common pathogen is S. aureus, with MRSA accounting for approximately one-fourth of all S. aureus patients. Additionally, extended-spectrum β-lactamase (ESBL)-producing G- bacteria have been identified, underscoring the importance of careful consideration during empirical antibiotic therapy.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)