pH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy.

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection.

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

Navigating Challenges in Cervicofacial Actinomycosis: A Case of Diagnostic Persistence and Multidisciplinary Collaboration.

Actinomycosis is a rare, chronic bacterial infection caused by Actinomyces species, characterized by granulomatous inflammation, abscesses, and sinus tracts. It primarily affects the cervicofacial region and often mimics other conditions such as malignancies or tuberculosis, complicating early diagnosis and treatment. This case report details an 18-year-old male with no known comorbidities, who presented with a two-week history of facial swelling, trismus, and discharging fistulas following an insect bite. The delay in seeking medical attention was due to initial symptom subsidence and challenges in accessing care. Diagnostic difficulties arose from inconclusive pus cultures and the lack of specialist resources at our facility. An incisional biopsy and subsequent histopathological examination revealed basophilic Gram-positive, non-acid fast filamentous bacteria and the Splendore-Hoeppli phenomenon, ultimately confirming actinomycosis. This case highlights the necessity of including actinomycosis in the differential diagnosis of facial infections and demonstrates the value of a multidisciplinary approach in managing complex cases with diagnostic and therapeutic challenges.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

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-MVL), 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 three weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 hours, the hydrogel formulation extended this release to 504 hours. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 hours and methicillin-resistant Staphylococcus aureus biofilms within 72 hours. It also eradicated pre-formed biofilms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in 96 and 120 hours, 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.

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review.

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.

The utility of disc space and vertebral body specimens cell count differential for the diagnosis of native vertebral osteomyelitis: a prospective cohort study.

BACKGROUND: Diagnostic methods for native vertebral osteomyelitis (NVO) often yield inconclusive results. Image-guided spine biopsies for culture are specific but diagnose NVO in only 50% of cases. Pre-exposure to antimicrobials further reduces diagnostic yield. Our study assesses the value of neutrophil percentage in disc space fluid and vertebral body (DS/VB) samples for diagnosing NVO. METHODS: Adults referred for spine biopsy at Mayo Clinic from August 2022 to September 2023 were consented and enrolled at the time of biopsy. Following routine specimen collection, the biopsy needle was rinsed in saline into an EDTA tube for cell analysis. NVO diagnosis required organism identification in spine tissue or blood and/or positive histopathology, and consistent symptoms and imaging. RESULTS: Sixty-eight patients were prospectively enrolled, comprising 14 with NVO and 54 with alternative diagnoses. The median biopsy sample polymorphonuclear (PMN) percentage for NVO patients was 80.5% (IQR 72.5-85.2), compared to 64.5% (IQR 54.0-69.0) for those without NVO (p < 0.001). Nine (64.3%) NVO patients received antibiotics within 10 days prior to spine biopsy. As a continuous measure, PMN differential showed a moderately strong ability in classifying NVO status with an area under ROC curve of 0.795; an optimal point on the curve of 71.5% corresponded to a sensitivity of 78.6%, specificity of 79.6%, negative predictive value of 93.5% and positive predictive value of 50.0%. CONCLUSION: PMN differential in DS/VB biopsies may serve as an effective diagnostic tool in the evaluation of patients with NVO particularly in ambiguous cases with an initially negative spine biopsy. Future efforts will aim to implement these findings within routine clinical practice.

A Case of Granulicatella adiacens Osteomyelitis and Mitral Valve Endocarditis.

Granulicatella adiacens is a nutritionally variant streptococci (NVS) that can cause various infections, including but not limited to endocarditis, osteomyelitis, pneumonia, and abscess. We report a case of an 80-year-old male who was found to have Granulicatella adiacens osteomyelitis and mitral valve endocarditis. Also included is a systematic review of osteomyelitis caused by Granulicatella adiacens.

Impact of SGLT2 inhibitors on lower limb complications: a mendelian randomization perspective.

Background: While Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in managing diabetes and reducing cardiovascular risk, concerns about their association with lower limb complications, including, osteomyelitis, ulcers, and peripheral artery disease (PAD), persist. This study employs Mendelian Randomization (MR) to assess the causal relationship between SGLT2 inhibitors and these lower limb safety outcomes. Methods: A two-sample drug-target MR approach was used, complemented by a one-sample MR and genetic association analysis. Six SNPs were selected as instrumental variables to proxy the effect of SGLT2 inhibition. Primary outcomes were major limb safety outcomes, including osteomyelitis, lower limb ulcers, PAD, and cellulitis. The primary analytical method was the generalized inverse variance-weighted (IVW) approach, along with several sensitivity analyses. Results: The MR analysis indicated no significant causal association between genetically proxied SGLT2 inhibition and most of the studied lower limb safety outcomes. However, a significant association with PAD was observed, necessitating careful interpretation due to discrepancies between IVW and MR-Egger results. Sensitivity analyses supported these findings, showing little evidence of heterogeneity or directional pleiotropy. Conclusion: This study suggests that SGLT2 inhibitors may not be significantly associated with an increased risk of most lower limb safety outcomes, including osteomyelitis, lower limb ulcers, and cellulitis, in patients with type 2 diabetes. However, the complex relationship with PAD highlights the need for further research. These findings contribute to the understanding of the safety profile of SGLT2 inhibitors, supporting their continued use in diabetes management while underlining the importance of continuous safety monitoring.

Unique Oral and Behavioral Manifestations of Post-COVID Multisystem Inflammatory Syndrome in a 5-year-old Child: A Rare Case Report.

Background: Multisystemic inflammatory syndrome (MIS) in the post-coronavirus disease (COVID) scenario is recognized in the pediatric population worldwide. However, no case report features jaw bone necrosis caused by self-mutilating injury noted during COVID treatment. Case description: This report is of a 5-year-old child affected by COVID. During the course of treatment, she presented with MIS and was treated with steroids and oxygen therapy. She was observed to have cardiac and gastrointestinal disorders. However, some psychiatric impairment caused her to pull out her lower anterior teeth, thus acting as an injury to the tissue and causing osteomyelitis. This necrotic bone tissue was excised surgically, and due to the loss of teeth, prosthetic rehabilitation was performed for the patient. Conclusion: This unique presentation of post-COVID manifestations of self-mutilating injury is alarming for the pediatric population. How to cite this article: Gala UP, Kalaskar RR. Unique Oral and Behavioral Manifestations of Post-COVID Multisystem Inflammatory Syndrome in a 5-year-old Child: A Rare Case Report. Int J Clin Pediatr Dent 2024;17(7):829-832.

Serratia Sacroiliitis Secondary to Intravenous Drug Use: A Case Report.

Serratia spp. are ubiquitous, opportunistic, and infectious organisms that have historically been known to infect the upper respiratory, urinary, and circulatory systems. This manuscript presents the case of a 35-year-old White female with a past medical history of polysubstance abuse, intravenous drug use (IVDU), and poor dentition who was admitted to a community hospital with complaints of lower back pain for 10 days following the recent completion of treatment for a suspected epidural abscess. Per her report, her last IVDU with fentanyl was 11 days prior, and she admitted to using various sources of water to inject her drugs. Magnetic resonance imaging with contrast was significant for possible infectious sacroiliitis, and blood cultures grew Serratia marcescens. Due to this patient's extensive IVDU history, in-patient ceftriaxone was chosen over discharging the patient with a peripherally inserted central catheter line. Serratia spp.bacteremia with concomitant septic sacroiliitis in the setting of IVDU is an extremely rare presentation. Due to the nonspecific presentation of sacroiliitis, multidrug resistance profile of Serratia spp., and high mortality rate associated with S. marcescens sepsis, early detection and diagnosis is paramount in similar patients with extensive risk factors.

MRI Findings of Acute on Chronic Osteomyelitis of Tibia in a 12-Year-Old Child.

Pediatric patients with osteomyelitis, a serious bone infection, have several difficulties. A 12-year-old child with an acute osteomyelitis diagnosis is the subject of this case study. The child had decreased limb function, a fever, and localized pain. Laboratory testing and diagnostic imaging procedures verified that Staphylococcus aureus was the culprit for the infection. Surgical debridement and intravenous antibiotics were used in combination for treatment. Therapy responses were constantly examined, and modifications were made in response to clinical and radiological findings. Prompt intensive treatment and early detection were essential for controlling the infection and averting long-term consequences. This example emphasizes the value of a multidisciplinary approach to treating pediatric osteomyelitis, pointing out possible directions for future study and presenting best practices.

Bone marrow edema in children: chronic nonbacterial osteomyelitis and its mimickers.

Bone marrow is a highly cellular tissue undergoing significant developmental and physiologic changes with age. Indeed, with maturation from pediatric to the adult age there is a progressive, centrifugal conversion from red to yellow bone marrow. Histological characteristics of bone marrow are reflected in MR image signal. MR is therefore extremely sensitive in detecting pathological changes which are mostly characterized by increased free water causing high signal intensity on T2. Among the numerous diseases causing bone marrow edema in children chronic nonbacterial osteomyelitis (CNO) certainly has to be mentioned. This idiopathic inflammatory disorder is characterized by nonspecific migrating symptoms like skeletal pain with phases of exacerbations and relapses with alternating acute and chronic MR signs and it is often a diagnosis of exclusion. Hence, with bone marrow edema, various features at imaging should be considered to differentiate malignancies such as osseous lymphoma, osteosarcoma, and Ewing's sarcoma as well as benign lesions like osteomyelitis, post-traumatic, or post-treatment bone marrow edema. The aim of this review is to recall the main characteristics of CNO and provide an overview of its main mimickers highlighting similarities and differences.

Methicillin-resistant Staphylococcus aureus in diabetic and non-diabetic foot infections.

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.

Multi-disciplinary management of neonatal acute osteomyelitis of jaws: A report of 2 cases.

Background: Early diagnosis of neonatal osteomyelitis is often challenging due to the rarity of such cases and here we are presenting 2 case reports to add to the existing deficient literature. Case 1: A 15-day-old male infant presented with swelling and pus discharge from the anterior region of the mandible. Repeated culture and sensitivity tests revealed a transition from disseminated methicillin-sensitive S. aureus sepsis to methicillin-resistant sepsis. Moreover, there was swelling of the left elbow and right thigh. The Clinical diagnosis made was acute osteomyelitis of mandible associated with disseminated neonatal sepsis (LONS). A multidisciplinary approach was taken for the management by surgical debridement of the lesion alongwith removal of associated primary tooth buds, under specific antibiotic coverage. Case 2: A 20-day old male infant reported with pus discharge from upper lateral region of mouth past 10days. Personal history revealed, abscess in mother's right breast. A soft fluctuant pus pocket with draining sinus was present w.r.t.alveolar region of 54. CT revealed an osteolytic lesion of labial cortex of alveolar ridge in maxillary right first molar region. Pus specimen culture and sensitivity revealed growth of Staphylococcus aureus (MSSA). The clinical diagnosis of acute osteomyelitis of maxillawas made. Initially, antibiotics were prescribed which did not help and finally, surgical debridement accompanied by extraction of 54 tooth bud was done. Conclusion: Acute osteomyelitis should always be considered as one of the differentials in infants with clinical signs of sepsis and Multidisciplinary management should be assured for the successful management of such cases.

[18F]FDG PET/CT Imaging Is Associated with Lower In-Hospital Mortality in Patients with Pyogenic Spondylodiscitis-A Registry-Based Analysis of 29,362 Cases.

BACKGROUND: While MRI is the primary diagnostic tool for the diagnosis of spondylodiscitis, the role of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT is gaining prominence. This study aimed to determine the frequency of [18F]FDG PET/CT usage and its impact on the in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric population. METHODS: We conducted a Germany-wide cross-sectional study from 2019 to 2021 using an open-access, Germany-wide database, analyzing cases with ICD-10 codes M46.2-, M46.3-, and M46.4- ('Osteomyelitis of vertebrae', 'Infection of intervertebral disc (pyogenic)', and 'Discitis unspecified'). Diagnostic modalities were compared for their association with in-hospital mortality, with a focus on [18F]FDG PET/CT. RESULTS: In total, 29,362 hospital admissions from 2019 to 2021 were analyzed. Of these, 60.1% were male and 39.9% were female, and 71.8% of the patients were aged 65 years and above. The overall in-hospital mortality rate was 6.5% for the entire cohort and 8.2% for the geriatric subgroup (p < 0.001). Contrast-enhanced (ce) MRI (48.1%) and native CT (39.4%) of the spine were the most frequently conducted diagnostic modalities. [18F]FDG PET/CT was performed in 2.7% of cases. CeCT was associated with increased in-hospital mortality (OR = 2.03, 95% CI: 1.90-2.17, p < 0.001). Cases with documented [18F]FDG PET/CT showed a lower frequency of in-hospital deaths (OR = 0.58, 95% CI: 0.18-0.50; p = 0.002). This finding was more pronounced in patients aged 65 and above (OR = 0.42, 95% CI: 0.27-0.65, p = 0.001). CONCLUSIONS: Despite its infrequent use, [18F]FDG PET/CT was associated with a lower in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric cohort. This study is limited by only considering data on hospitalized patients and relying on the assumption of error-free coding. Further research is needed to optimize diagnostic approaches for spondylodiscitis.

Risk factors for fracture-related infections after low-velocity gunshot fractures to the pelvis.

BACKGROUND: Although treatments have improved dramatically in recent years, mortality following gunshot wounds (GSW) to the pelvis continue to range between 3 and 20 %. This project was designed to determine the incidence and risk factors associated with pelvic fracture-related infection (FRI) following GSWs to the pelvis given the paucity of evidence regarding this complication. METHODS: A retrospective review of 13 years (1/2010-12/2022) of patients with GSW to the pelvis was performed. Patients meeting inclusion criteria underwent chart review for the development of pelvic FRI and the following additional data elements were extracted: demographics, presence and type of bowel injury, operations performed, complications, use of postoperative antibiotics (≤24 h vs. >24 h), surgical osseous debridement, presence of retained bullet fragments, and bullet trajectory. Discrete variables were analyzed using Wilcoxon rank-sum test, chi-square, and Fischer's exact test. Pearson correlation coefficients were calculated for continuous variables. RESULTS: 242 patients were included in the study. Concomitant bowel injury was present in 108 patients (45 %). Eleven patients (4.5 %) developed FRI, all of whom had a concomitant bowel injury (p < 0.001). Neither the presence of retained bullet fragments nor the bullet trajectory (through bowel before the bone) was associated with FRI. Antibiotic duration >24 h was not associated with a lower rate of pelvic FRI. CONCLUSION: Development of FRI after a GSW to the pelvis occurs in 4.5 % of patients and is significantly associated with concomitant bowel injury, specifically colonic injury. These findings can be used to help guide further studies on the role of prophylactic antibiotics or other strategies to prevent pelvic FRI.

Evaluating diagnostic tools, outcome measures and antibiotic approach in diabetic foot osteomyelitis: a scoping review and narrative synthesis.

INTRODUCTION: Diabetic foot osteomyelitis (DFO) is a significant complication of diabetic foot disease; however, diagnosis remains challenging and treatment success is difficult to ascertain. Literature in this space that has utilized varying diagnostic criteria and ideal outcome measures for success is unclear. AREAS COVERED: This scoping review assesses methods of diagnosis of DFO and definitions of treatment outcomes in the literature assessing antibiotic therapy for treatment of DFO. EXPERT OPINION: There is a lack of consensus in the design of diabetic foot trials, resulting in difficulty for clinicians to assess and manage serious conditions such as DFO. The cure for DFO is challenging to ascertain and treatment failure may be a better approach to assess outcomes in research assessing the efficacy of antibiotic therapy. In the absence of gold-standard diagnostic tools, practical approaches to outcome assessment may allow for greater clinical applicability of available data.

Extra-Articular Abscess Expansion as a Specific Complication of Septic Arthritis of the Shoulder Joint: Report of Three Cases with Extension of the Infection through the Biceps Groove Producing a Large Abscess.

BACKGROUND: Septic arthritis of shoulder is a rare clinical entity as the metaphysis is extracapsular and there is no communication between epiphyseal and metaphyseal vessels. Septic arthritis of the shoulder joint is a diagnostic and surgical emergency because joint destruction develops rapidly and can cause significant morbidity and mortality. Unusual complications of septic arthritis of the shoulder joint may include extra-articular abscess extension to the upper arm through the biceps groove and osteomyelitis of the greater tuberosity. CASE PRESENTATION: Septic arthritis of the shoulder, if left untreated, can lead to complications such as extra-articular abscess extension and osteomyelitis. Three patients with septic arthritis of the shoulder joint with no clear history of trauma were reported in this study. The initial presentation was pseudoparalysis with upper arm swelling. MRI diagnosed septic arthritis of shoulder joint together with an upper arm abscess. Arthroscopic debridement with through irrigation and open drainage of the extra-articular abscess extension to the upper arm improved both the shoulder pain and abscess completely. However, if shoulder pain or abnormalities in laboratory findings continue after initial treatment, uncontrolled septic arthritis or secondary osteomyelitis are possibilities that should be concerned. MRI is a useful tool for detecting those atypical complications. CONCLUSIONS: Rarely, septic arthritis of the shoulder joint can extend to the upper arm through the biceps tendon groove and cause an abscess. Also, acute osteomyelitis of the tuberosity should be considered in patients with long-standing refractory septic arthritis of the shoulder joint who have continued pain and uncontrolled laboratory findings after initial treatment.

Skull base osteomyelitis due to bilateral acute otitis media: Case report and literature review.

Skull base osteomyelitis is a rare and serious condition that primarily affects immunocompromised individuals and can be life threatening if not treated promptly. It can have various origins, with the most common being an extension of necrotizing external otitis. It is difficult to diagnose due to a wide array of clinical presentations. Imaging plays an important role in the diagnosis, identification of the possible source of infection, the extent of the disease, the pattern of spread and identification of associated complications. Early diagnosis is crucial to promptly initiate appropriate treatment. We report here a rare case of a 68-year-old patient presenting with skull base osteomyelitis resulting from bilateral otitis media, which is a rare condition.