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.

Case report of minimally invasive spinal endoscopic debridement and pedicle screw fixation for severe spinal infection of the lumbosacral spine.

Background: Surgical treatment of spinal infections, refractory to medical treatments, is increasing in incidence. Here, we present a unique case of discitis secondary to an iatrogenic cause, spinal steroid injection, that resulted in acute neurology, ventral phlegmon, and osteomyelitis requiring multiple surgical interventions for treatment. Case Description: With the adoption of minimally invasive spinal surgery, the patient underwent full endoscopic debridement and decompression at our hospital. The endoscopic technique offers a unique avenue to the anatomically difficult ventral phlegmon for surgical excision, cultures, and pathogen identification. The endoscopic debridement was paired with percutaneous pedicle screw fixation to stabilize the spine from the worsening bone destruction. Outcome: The patient recovered well postoperatively, with the resolution of her neurological symptoms and improved mobility. Conclusions: Full endoscopic spinal debridement and decompression is a powerful tool to manage severe spinal discitis and preliminary studies encourage its adoption in surgical practices.

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.

Osteomyelitis and Septic Arthritis of the Foot and Ankle: Imaging Update.

Radiography is considered the first-line screening exam for clinically suspected osteomyelitis. However, additional evaluation is generally needed. MRI is the definitive diagnostic exam with high sensitivity and specificity combined with excellent anatomic definition. Gadolinium contrast can be useful to detect areas of devitalization before surgery. Bone marrow edema on fluid-sensitive images and low signal intensity on T1-weighted images in the presence of secondary MRI findings, including ulcer, sinus tract, and cellulitis with or without abscess are typical findings of osteomyelitis. If MRI is contraindicated, three phase bone scan can be used. Early diagnosis and treatment is essential.

A 65-Year-Old Female with Missed Open Clavicle Fracture and Subsequent Fracture-Related Infection, Treated with Distal Clavicle Resection.

Introduction: Open clavicle fractures are rare, and there are no current reported cases in the literature of a missed open clavicle with resultant fracture-related infection and osteomyelitis. Case Report: We present a 65-year-old female with no reported medical history, who presented to our institution with left clavicular pain and wound drainage 8 days after she was struck by a motor vehicle in her home country of Guyana. She was found to have a missed open clavicle fracture with an associated severe infection. She was subsequently treated with irrigation, debridement, and distal clavicle excision. Conclusion: We present this unique case with a potential procedure which could prove beneficial in cases of infection, trauma, or oncologic lesions in which the distal clavicle is deemed unsalvageable.

A retrospective study of the anterolateral thigh perforator flap in the treatment of chronic osteomyelitis of the leg with skin defects.

Background: As a chronic inflammatory process, chronic osteomyelitis is caused by bacterial infections that lead to bone destruction. This disease is more common in patients with open fractures and those undergoing multiple surgical procedures after trauma. We aimed to provide a comprehensive overview and critical assessment of the therapeutic efficacy of the anterolateral thigh (ALT) perforator flap in the management of chronic osteomyelitis with dermatologic and soft tissue imperfections localized in the lower extremity. Methods: A retrospective analysis involving a cohort of 16 patients who underwent ALT perforator flap reconstruction for the management of chronic osteomyelitis in the calf region that manifested with integumentary deficiencies was conducted. Results: During the follow-up period spanning from 4 months to 2 years, all 16 patients who underwent ALT perforator flap transplantation exhibited flap viability. Among these cases, 15 patients made a full recovery from the infection and 1 patient had partial survival. Among the 15 cases, 2 patients developed vascular crisis (owing to venous thrombosis during surgical exploration). One patient had a relapse of the disease 1-year post-surgery. The success rate of this surgical method was 15/16, and the surgical complications included flap crisis, flap necrosis, delayed wound healing, and recurrence of infection. Conclusion: The ALT perforator flap, which can cover bone and soft tissues and effectively control infections, can be applied to the treatment of chronic osteomyelitis of the lower limbs with skin defects. Overall, the muscle flap fills the dead space and medullary cavity and skin flap covers the skin defect.

Characterising the role of enolase in a stable Small Colony Variant of Staphylococcus aureus isolated from a diabetic foot infection patient with osteomyelitis.

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.

Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study.

OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

Wohlfahrtiimonas chitiniclastica Bacteremia: A Rare Case of a Male With Maggot-Infested Lower Extremity Wounds.

Wohlfahrtiimonas chitiniclastica (W. chitiniclastica) is an emerging gram-negative bacillus rarely found in patients presenting with fly myiasis or parasitic larvae infection. Here, we present the case of a 58-year-old male who presented with W. chitiniclastica bacteremia from lower extremity wounds complicated by fly larvae infestation. Blood cultures were analyzed with matrix-assisted laser desorption ionization-time of flight mass spectrometry, which identified W. chitiniclastica. The patient was treated with empiric antibiotic therapy with piperacillin-tazobactam and de-escalated to ceftriaxone. We discuss the potential impact of environmental interactions with zoonotic vectors and the concern for the increasing incidence of this new emerging zoonotic infection. This appears to be the first reported case of W. chitiniclastica bacteremia in the southern United States and demonstrates a growing list of climates and locations in which this organism can be present. Further evaluation of potential vectors for W. chitiniclastica continues to be a priority for how cases are distributed and can present in patients.

Bacterial chondronecrosis with osteomyelitis lameness in broiler chickens and its implications for welfare, meat safety, and quality: a review.

The exponential increase in global population continues to present an ongoing challenge for livestock producers worldwide to consistently provide a safe, high-quality, and affordable source of protein for consumers. In the last 50 years, the poultry industry has spearheaded this effort thanks to focused genetic and genomic selection for feed-efficient, high-yielding broilers. However, such intense selection for productive traits, along with conventional industry farming practices, has also presented the industry with a myriad of serious issues that negatively impacted animal health, welfare, and productivity-such as woody breast and virulent diseases commonly associated with poultry farming. Bacterial chondronecrosis with osteomyelitis (BCO) lameness is one such issue, having rapidly become a key issue affecting the poultry industry with serious impacts on broiler welfare, meat quality, production, food safety, and economic losses since its discovery in 1972. This review focuses on hallmark clinical symptoms, diagnosis, etiology, and impact of BCO lameness on key issues facing the poultry industry.

Lumbosacral Discitis and Osteomyelitis after Sacrocolpopexy: A Case Series and Review of Management.

INTRODUCTION AND HYPOTHESIS: Lumbosacral discitis and osteomyelitis constitute a rare but devastating complication after mesh sacrocolpopexy for pelvic organ prolapse. METHODS: We present a case series of 3 patients at a single institution and a literature review of 30 patients suffering from this complication along with presenting symptoms, evaluation with laboratory and imaging findings, and management. RESULTS: Lumbosacral discitis can present after sacrocolpopexy of any route (abdominal, laparoscopic, and robotic) and with various suture types and tacking devices. Patients presented with lower back pain at varying time frames and with elevated inflammatory markers, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). CONCLUSION: The majority of cases required both excision of pelvic mesh via laparotomy or laparoscopy in combination with an extended course of intravenous (IV) antibiotics.

Pediatric calcaneal osteomyelitis: an analysis of literature-reported 128 cases.

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.

Single nucleotide polymorphisms in the development of osteomyelitis and prosthetic joint infection: a narrative review.

Currently, despite advancements in diagnostic and therapeutic modalities, osteomyelitis and prosthetic joint infection (PJI) continue to pose significant challenges for orthopaedic surgeons. These challenges are primarily attributed to the high degree of heterogeneity exhibited by these disorders, which are influenced by a combination of environmental and host factors. Recent research efforts have delved into the pathogenesis of osteomyelitis and PJI by investigating single nucleotide polymorphisms (SNPs). This review comprehensively summarizes the current evidence regarding the associations between SNPs and the predisposition to osteomyelitis and PJI across diverse populations. The findings suggest potential linkages between SNPs in genes such as IL-1, IL-6, IFN-γ, TNF-α, VDR, tPA, CTSG, COX-2, MMP1, SLC11A1, Bax, NOS2, and NLRP3 with the development of osteomyelitis. Furthermore, SNPs in genes like IL-1, IL-6, TNF-α, MBL, OPG, RANK, and GCSFR are implicated in susceptibility to PJI. However, it is noted that most of these studies are single-center reports, lacking in-depth mechanistic research. To gain a more profound understanding of the roles played by various SNPs in the development of osteomyelitis and PJI, future multi-center studies and fundamental investigations are deemed necessary.

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.

Gentamicin and clindamycin antibiotic-eluting depot technology eradicates S. aureus in an implant-associated osteomyelitis pig model without systemic antibiotics.

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.

The role of hyperbaric oxygen treatment in the management of spondylodiscitis.

Introduction: This study analysed treatment outcomes in a patient cohort diagnosed with spondylodiscitis, who received adjunct hyperbaric oxygen treatment (HBOT) in addition to antibiotic therapy at our clinic. Important considerations included the timing of HBOT initiation on treatment success, and recurrence rates. Methods: We retrospectively reviewed the records of all patients diagnosed with spondylodiscitis who received HBOT at the Underwater and Hyperbaric Medicine Clinic in Gulhane Training and Research Hospital, between 1 November 2016 and 25 October 2022. The patients received HBOT at 243.2 kPa for a total of 120 minutes per session, once daily for five days a week for a total of 30 sessions. Results: Twenty-five patients with spondylodiscitis were evaluated before and after combination HBOT and targeted antibiotic treatment. After treatment, patients had lower median (range) visual analogue pain scores (8 [4-10] vs 3 [0-7], P < 0.001) and C-reactive protein (22.3 [4.3-79.9] mg·L⁻¹ vs 6.8 [0.1-96.0] mg·L⁻¹, P = 0.002) and lower mean (standard deviation) white blood cell counts (8.8 [3.5] x 109·L⁻¹ vs 6.1 [1.6] x 109·L⁻¹, P = 0.002). When patients were examined (median) 48 months (2-156 months) after the completion of treatment, there were no persistent cases of spondylodiscitis. Conclusions: Combination HBOT with targeted antibiotic therapy effectively managed our cohort of patients diagnosed with spondylodiscitis. Hyperbaric oxygen treatment was safe, with no complications experienced. Moreover, HBOT may have helped to eliminate persistence and recurrence of symptoms with long term follow-up. A randomised controlled study with a larger number of patients is needed for more definitive conclusions.

Pediatric Necrotizing Otitis Externa: A Scoping Review.

OBJECTIVE: This review sought to answer the following research question: What are the characteristics of pediatric necrotizing otitis externa (NOE)? Moreover, we wanted to highlight the clinical importance of the current limitations in the literature. METHODS: A scoping review was performed to determine what is known about NOE in the pediatric population. Four databases (COCHRANE Library, CINAHL, PubMed, and Scopus) were queried for articles published in English between 1976 to 2022. Variables extracted included comorbidities, demographics, outcomes, and treatment. RESULTS: A total of 20 studies (N = 439) reported sufficient measures to be included in the review. Patients with NOE had a mean age of 10.0 years (range 2 months to 14 years) with a male-to-female gender ratio of 1.1:1. Mean length of hospital stay was 2.9 days (95%CI: 2.7-3.0). Demographics included 45.4% Caucasian, 6.0% African American, and 2.7% Asian/Pacific Islander. Less than 5% of patients had diabetes, while other reported comorbidities included neutropenia (n = 6), anemia (n = 5), dehydration/malnutrition (n = 4), Stevens Johnson Syndrome (n = 2), some form of immunosuppression/organ transplantation (n = 2), thrombocytopenia (n = 2), and leukopenia (n = 2). There have been no reported deaths from NOE in children. CONCLUSIONS: In the adult population NOE most commonly affects patients with diabetes, but our review reveals that diabetes does not appear to play as big a role in children. The disease seems to commonly affect patients with immunosuppression or severe health conditions. Complications such as cranial nerve palsies appear to be more common in the pediatric population. Specifically, the role of biopsy and culture in the treatment of pediatric NOE is stressed as they are important in treatment decisions.