Infectious Aspects of Chronic Wounds.

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.

Clinical outcomes in people with diabetes-related foot infections: Analysis from a limb preservation service infection database.

BACKGROUND: Diabetes-related foot infections are common and represent a significant clinical challenge. There are scant data about outcomes from large cohorts. The purpose of this study was to report clinical outcomes from a large cohort of people with diabetes-related foot infections. METHODS: A tertiary referral hospital limb preservation service database was established in 2018, and all new episodes of foot infections were captured prospectively using an electronic database (REDCap). People with foot infections between January 2018 and May 2023, for whom complete data were available on infection episodes, were included. Infection outcomes were compared between skin and soft tissue infections (SST-DFI) and osteomyelitis (OM) using chi-square tests. RESULTS: Data extraction identified 647 complete DFI episodes in 397 patients. The data set was divided into two cohorts identifying each infection episode and its severity as either SST-DFI (N = 326, 50%) or OM (N = 321, 50%). Most infection presentations were classified as being moderate (PEDIS 3 = 327, 51%), with 36% mild (PEDIS 2 = 239) and 13% severe (PEDIS 4 = 81). Infection resolution occurred in 69% (n = 449) of episodes with failure in 31% (n = 198). Infection failures were more common with OM than SST-DFI (OM = 140, 71% vs. SST-DFI = 58, 29%, p < 0.00001). In patients with SST-DFI a greater number of infection failures were observed in the presence of peripheral arterial disease (PAD) compared to the patients without PAD (failure occurred in 30% (31/103) of episodes with PAD and 12% (27/223) of episodes without PAD; p < 0.001). In contrast, the number of observed infection failures in OM episodes were similar in patients with and without PAD (failure occurred in 45% (57/128) of episodes with PAD and 55% (83/193) of episodes without PAD; p = 0.78). CONCLUSIONS: This study provides important epidemiological data on the risk of poor outcomes for DFI and factors associated with poor outcomes in an Australian setting. It highlights the association of PAD and treatment failure, reinforcing the need for early intervention to improve PAD in patients with DFI. Future randomised trials should assess the benefits of revascularisation and surgery in people with DFI and particularly those with OM where outcomes are worse.

Applying 3D-printed prostheses to reconstruct critical-sized bone defects of tibial diaphysis (> 10 cm) caused by osteomyelitis and aseptic non-union.

BACKGROUND: Clinical repair of critical-sized bone defects (CBDs) in the tibial diaphysis presents numerous challenges, including inadequate soft tissue coverage, limited blood supply, high load-bearing demands, and potential deformities. This study aimed to investigate the clinical feasibility and efficacy of employing 3D-printed prostheses for repairing CBDs exceeding 10 cm in the tibial diaphysis. METHODS: This retrospective study included 14 patients (11 males and 3 females) with an average age of 46.0 years. The etiologies of CBDs comprised chronic osteomyelitis (10 cases) and aseptic non-union (4 cases), with an average defect length of 16.9 cm. All patients underwent a two-stage surgical approach: (1) debridement, osteotomy, and cement spacer implantation; and (2) insertion of 3D-printed prostheses. The interval between the two stages ranged from 8 to 12 weeks, during which the 3D-printed prostheses and induced membranes were meticulously prepared. Subsequent to surgery, patients engaged in weight-bearing and functional exercises under specialized supervision. Follow-up assessments, including gross observation, imaging examinations, and administration of the Lower Extremity Functional Scale (LEFS), were conducted at 3, 6, and 12 months postoperatively, followed by annual evaluations thereafter. RESULTS: The mean postoperative follow-up duration was 28.4 months, with an average waiting period between prosthesis implantation and weight-bearing of 10.4 days. At the latest follow-up, all patients demonstrated autonomous ambulation without assistance, and their LEFS scores exhibited a significant improvement compared to preoperative values (30.7 vs. 53.1, P < 0.001). Imaging assessments revealed progressive bone regeneration at the defect site, with new bone formation extending along the prosthesis. Complications included interlocking screw breakage in two patients, interlocking screw loosening in one patient, and nail breakage in another. CONCLUSIONS: Utilization of 3D-printed prostheses facilitates prompt restoration of CBDs in the tibial diaphysis, enabling early initiation of weight-bearing activities and recovery of ambulatory function. This efficacious surgical approach holds promise for practical application.

The diabetic sausage toe: Prevalence, presentation and outcomes.

Osteomyelitis (OM) in diabetic foot infection could have many presentations such as an infected ulcer spreading to the bone or superimposed to Charcot neuroarthropathy. However, the sausage toe as a diabetic OM presentation was very rarely investigated; therefore, this study aims to assess the prevalence and signs of this presentation along with treatment modalities and outcomes. This is a retrospective series of patients presenting a sausage toe on admission. Several methods were conducted to diagnose OM, and three treatment modalities were applied. Two groups were compared: acute and chronic sausage toes. Outcomes were defined as sausage toe prevalence, ulcer location, OM prevalence, and comparative treatment results. Out of 82 diabetic toe infection cases, 24 (30%) presented as 'sausage toe'. The side of the proximal interphalangeal joint of the lateral toes was the most frequent ulcer location (50%), mostly on the dorsal aspect followed by the side aspect. There were 15 (62.5%) acute cases and 9 (37.5%) chronic cases. MRI showed signs of OM in 21 (87.5%) cases and signs of septic arthritis in 3 (12.5%) cases. At the final follow-up, a successful treatment was recorded in five (20%) cases with antibiotics alone. Out of the 19 (42%) procedures, conservative surgery was performed successfully in 8 (58%) cases while amputation was needed in 11 (45.8%) cases. There was no significant difference in amputation frequency between acute and chronic groups. This is the first study documenting the sausage toe as a prevalent presentation of diabetic toe infection. The deformity is conclusive of deep infection with a very high osteomyelitis frequency. Surgery is often required for infection control and healing, mainly for chronic cases, and treatment outcomes did not differ between acute and chronic sausage toe groups. It could be beneficial to include this entity in the diabetic wound classification systems.

Integrative gene expression analysis and animal model reveal immune- and autophagy-related biomarkers in osteomyelitis.

BACKGROUND: Osteomyelitis (OM) is recognized as a significant challenge in orthopedics due to its complex immune and inflammatory responses. The prognosis heavily depends on timely diagnosis, accurate classification, and assessment of severity. Thus, the identification of diagnostic and classification-related genes from an immunological standpoint is crucial for the early detection and tailored treatment of OM. METHODS: Transcriptomic data for OM was sourced from the Gene Expression Omnibus (GEO) database, leading to the identification of autophagy- and immune-related differentially expressed genes (AIR-DEGs) through differential expression analysis. Diagnostic and classification models were subsequently developed. The CIBERSORT algorithm was utilized to examine immune cell infiltration in OM, and the relationship between OM clusters and various immune cells was explored. Key AIR-DEGs were further validated through the creation of OM animal models. RESULTS: Analysis of the transcriptomic data revealed three AIR-DEGs that played a significant role in immune responses and pathways. Nomogram and receiver operating characteristic curve analyses were performed, demonstrating excellent diagnostic capability for differentiating between OM patients and healthy individuals, with an area under the curve of 0.814. An unsupervised clustering analysis discerned two unique patterns of autophagy- and immune-related genes, as well as gene patterns. Further exploration into immune infiltration exhibited notable variances across different subtypes, especially between OM cluster 1 and gene cluster A, highlighting their potential role in mitigating inflammatory responses by regulating immune activities. Moreover, the mRNA and protein expression levels of three AIR-DEGs in the animal model were aligned with those in the training and validation data sets. CONCLUSIONS: From an immunological perspective, a diagnostic model was successfully developed, and two distinct clustering patterns were identified. These contributions offer a significant resource for the early detection and personalized immunotherapy of patients with OM.

Ruthenibacterium lactatiformans isolated from a human blood culture: a first report.

BACKGROUND: Ruthenibacterium lactatiformans, a Gram-stain-negative, rod-shaped, obligate anaerobic bacterium of the Oscillospiraceae family, has not been previously reported in human infections. This study reports the first case of bacteraemia and potential vertebral osteomyelitis caused by Ruthenibacterium lactatiformans. CASE PRESENTATION: An 82-year-old man with a history of diabetes, chronic renal failure, and prior spinal surgery for spondylolisthesis and spinal stenosis presented with fever and lower back pain. Magnetic resonance imaging revealed multiple vertebral osteomyelitis lesions. Initial blood cultures identified methicillin-resistant Staphylococcus aureus (MRSA), which prompted vancomycin treatment. However, repeated blood cultures not only confirmed persistent MRSA, but also detected Gram-negative bacilli (GNB). Despite surgical removal of the spinal hardware and antimicrobial therapy, the patient's osteomyelitis worsened, necessitating transfer for further management. Subsequent analysis using 16S rRNA gene sequencing identified the GNB as Ruthenibacterium lactatiformans. CONCLUSIONS: This is the first documented instance of human infection with Ruthenibacterium lactatiformans, signifying its pathogenic potential in vertebral osteomyelitis. The involvement of anaerobic bacteria and the possibility of polymicrobial infections complicate the diagnosis and treatment of vertebral osteomyelitis. This report underscores the need for caution when identifying the causative organism and selecting an appropriate treatment.

Age-related dysregulation of CXCL9/10 in monocytes is linked to impaired innate immune responses in a mouse model of Staphylococcus aureus osteomyelitis.

BACKGROUND: Age-associated impairments in innate immunity are believed to be a causative factor responsible for severe pathogenesis of Staphylococcus aureus (S. aureus) infection in the bone tissue. However, the basis for age-associated decline in innate immune response upon S. aureus infection remains poorly understood. RESULTS: Our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis show up-regulated CXCL9 and CXCL10 (CXCL9/10), which is further confirmed in vitro and in vivo by the present study. Notably, monocytes are a main source for CXCL9/10 production in bone marrow upon S. aureus challenge, but this response declines in middle-aged mice. Interestingly, conditional medium of bone marrow monocytes from middle-aged mice has a strikingly decreased effect on bactericidal functions of neutrophils and macrophages compares with that from young mice. We further show that activation of CXCL9/10-CXCR3 axis between monocytes and macrophages/neutrophils promotes the bactericidal function of the cells, whereas blocking the axis impairs such function. Importantly, treatment with either exogenous CXCL9 or CXCL10 in a middle-aged mice model enhances, while pharmacological inhibition of CXCR3 in young mice model impairs, bacterial clearance and bone marrow structure. CONCLUSIONS: These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes.

Destructive Cryptococcal Osteomyelitis Mimicking Tuberculous Spondylitis.

BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 µm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.

Bone and joint infections due to melioidosis; diagnostic and management strategies to optimise outcomes.

BACKGROUND: Melioidosis, a life-threatening infection caused by the gram negative bacterium Burkholderia pseudomallei, can involve almost any organ. Bone and joint infections (BJI) are a recognised, but incompletely defined, manifestation of melioidosis that are associated with significant morbidity and mortality in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We identified all individuals with BJI due to B. pseudomallei managed at Cairns Hospital in tropical Australia between January 1998 and June 2023. The patients' demographics, their clinical findings and their treatment were correlated with their subsequent course. Of 477 culture-confirmed cases of melioidosis managed at the hospital during the study period, 39 (8%) had confirmed BJI; predisposing risk factors for melioidosis were present in 37/39 (95%). However, in multivariable analysis only diabetes mellitus was independently associated with the presence of BJI (odds ratio (95% confidence interval): 4.04 (1.81-9.00), p = 0.001). BJI was frequently only one component of multi-organ involvement: 29/39 (74%) had infection involving other organs and bacteraemia was present in 31/39 (79%). Of the 39 individuals with BJI, 14 (36%) had osteomyelitis, 8 (20%) had septic arthritis and 17 (44%) had both osteomyelitis and septic arthritis; in 32/39 (83%) the lower limb was involved. Surgery was performed in 30/39 (77%). Readmission after the initial hospitalisation was necessary in 11/39 (28%), 5/39 (13%) had disease recrudescence and 3/39 (8%) had relapse; 4/39 (10%) developed pathological fractures. ICU admission was necessary in 11/39 (28%) but all 11 of these patients survived. Only 1/39 (3%) died, 138 days after admission, due to his significant underlying comorbidity. CONCLUSIONS: The case-fatality rate from melioidosis BJI in Australia's well-resourced health system is very low. However, recrudescence, relapse and orthopaedic complications are relatively common and emphasise the importance of collaborative multidisciplinary care that includes early surgical review, aggressive source control, prolonged antibiotic therapy, and thorough, extended follow-up.

Unique Presentation of Asymptomatic Bacteriuria, Vertebral Osteomyelitis, and Iliopsoas Abscess Due to Klebsiella pneumonia in a 73-Year-Old Man with Type 2 Diabetes Mellitus on Empagliflozin.

BACKGROUND Sodium-glucose co-transporter 2 inhibitors (SGLT2), such as empagliflozin, used to treat type 2 diabetes mellitus (DM), can increase the risk of infections, including urinary tract infections and osteomyelitis, especially in elderly patients. The use of SGLT2 inhibitors has been increasing dramatically in the last few years. Therefore, their adverse effects and complications have also been increasing. Herein, this report describes a 73-year-old man with type 2 DM treated with empagliflozin presenting with asymptomatic bacteriuria, vertebral osteomyelitis and iliopsoas abscess due to Klebsiella pneumoniae. CASE REPORT We report a 73-year-old man with DM on empagliflozin who presented with back pain of 1-month duration with elevated inflammatory markers. On lumbar spine magnetic resonance imaging (MRI), he was found to have lumbar vertebral osteomyelitis and left iliopsoas abscess. His symptoms were improved with abscess drainage and antimicrobial therapy. The source of infection was most likely asymptomatic bacteriuria, which may have been secondary to empagliflozin treatment, as evidenced by the urine, the blood, the bone and abscess cultures revealing growth of Klebsiella pneumoniae with the same susceptibility profile. CONCLUSIONS This particular case reinforces the significance of potential complications of DM and SGLT2 inhibitors' adverse effects, especially the increased risk of infections, and can aid clinicians in expanding the differential and enabling them to reach an accurate diagnosis and appropriate management. Although vertebral osteomyelitis is a less common cause of back pain, physicians should keep it in the differential diagnosis whenever a patient's back pain is chronic and associated with motor weakness.

3D-printed titanium porous prosthesis combined with the Masquelet technique for the management of large femoral bone defect caused by osteomyelitis.

BACKGROUND: The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. METHODS: Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. RESULTS: The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant-bone interface in 10 patients. CONCLUSION: The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.

Chronic Diffuse Sclerosing Osteomyelitis of the Mandible: The Use of Bisphosphonates as a Treatment for a Rare and Challenging Condition.

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies.

A semi-automated cell tracking protocol for quantitative analyses of neutrophil swarming to sterile and S. aureus contaminated bone implants in a mouse femur model.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S. aureus on a contaminated transfemoral implant in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP/EGFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-user reliability for all outcomes (ICC > 0.96; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.

Clinical characteristics and outcomes associated with culture-negative status in limb osteomyelitis patients.

Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

Application of AI-assisted MRI for the identification of surgical target areas in pediatric hip and periarticular infections.

OBJECTIVE: To develop an AI-assisted MRI model to identify surgical target areas in pediatric hip and periarticular infections. METHODS: A retrospective study was conducted on the pediatric patients with hip and periarticular infections who underwent Magnetic Resonance Imaging(MRI)examinations from January 2010 to January 2023 in three hospitals in China. A total of 7970 axial Short Tau Inversion Recovery (STIR) images were selected, and the corresponding regions of osteomyelitis (label 1) and abscess (label 2) were labeled using the Labelme software. The images were randomly divided into training group, validation group, and test group at a ratio of 7:2:1. A Mask R-CNN model was constructed and optimized, and the performance of identifying label 1 and label 2 was evaluated using receiver operating characteristic (ROC) curves. Calculation of the average time it took for the model and specialists to process an image in the test group. Comparison of the accuracy of the model in the interpretation of MRI images with four orthopaedic surgeons, with statistical significance set at P < 0.05. RESULTS: A total of 275 patients were enrolled, comprising 197 males and 78 females, with an average age of 7.10 ± 3.59 years, ranging from 0.00 to 14.00 years. The area under curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 1 were 0.810, 0.976, 0.995, 0.969, 0.922, and 0.957, respectively. The AUC, accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 2 were 0.890, 0.957, 0.969, 0.915, 0.976, and 0.972, respectively. The model demonstrated a significant speed advantage, taking only 0.2 s to process an image compared to average 10 s required by the specialists. The model identified osteomyelitis with an accuracy of 0.976 and abscess with an accuracy of 0.957, both statistically better than the four orthopaedic surgeons, P < 0.05. CONCLUSION: The Mask R-CNN model is reliable for identifying surgical target areas in pediatric hip and periarticular infections, offering a more convenient and rapid option. It can assist unexperienced physicians in pre-treatment assessments, reducing the risk of missed and misdiagnosis.

Malassezia restricta as an unexpected cause of infectious osteomyelitis diagnosed by metagenomic sequencing: a case report and literature review.

BACKGROUND: Malassezia restricta, a lipophilic and lipodependent yeast belonging to the basidiomycetes group, is an opportunistic fungal pathogen associated with various skin diseases, including seborrheic dermatitis and dandruff. Typically, Malassezia infection in neonates manifests as fungemia or hematogenous dissemination to the bone or lungs. However, vertebral osteomyelitis caused by these fungi is rarely reported owing to non-specific clinical presentations and laboratory/imaging findings. The Pathogen Metagenomics Sequencing (PMseq) technique enables direct high-throughput sequencing of infected specimens, facilitating the rapid and accurate detection of all microorganisms in clinical samples through comprehensive reports. CASE PRESENTATION: A 52-year-old male was admitted to our hospital on July 20, 2022 with a 3-month history of ambulatory difficulties and localized low back pain. Magnetic Resonance Imaging (MRI) examination of the spinal column revealed irregular bone destruction affecting the L2, L3, and L5 vertebral bodies. Additionally, low T1 and high T2 intensity lesions were observed at the intervertebral discs between L3 and L5. The presumptive diagnosis of tuberculous spondylitis was made based on the imaging findings, despite negative results in all mycobacterium tests. However, the patient exhibited no improvement after receiving regular anti-tuberculosis treatment for 3 months. Subsequent MRI revealed an expansive abnormal signal within the vertebral body, leading to progressive bone destruction. The absence of spinal tuberculosis or other infective microorganisms was confirmed through culture from blood and pathological tissue from the L4 vertebral body. Subsequently, PMseq was performed on the specimens, revealing M. restricta as the predominant pathogen with the highest relative abundance value. The pathological examination revealed the presence of fungal mycelium in the L4 vertebral body, with positive findings on periodic Schiff-methenamine and periodic acid-Schiff staining. The anti-tuberculosis treatment was discontinued, and an antifungal combination of fluconazole and voriconazole was administered. All symptoms were resolved after 7 consecutive months of treatment, and the patient was able to ambulate autonomously. Vertebral lesions were reduced on MRI during the 13-month follow-up. CONCLUSIONS: M. restricta is not a commonly recognized pathogen associated with infectious vertebral osteomyelitis. However, PMseq can aid in diagnosis, timely treatment, and decision making for some non-specific infectious diseases.

Single versus two-stage management of long-bone chronic osteomyelitis in adults: a systematic review and meta-analysis.

BACKGROUND: Chronic osteomyelitis is a debilitating bone infection, characterized by a persistent infection over months to years, poses diagnostic and therapeutic challenges due to its insidious nature and potential for severe bone and soft tissue destruction. This systematic review and meta-analysis aims to review the literature on the treatment of chronic osteomyelitis in long bones and assess cure rates in single versus two-stage surgery. METHODS: Following the PRISMA guidelines and registered with PROSPERO (ID: CRD42021231237), this review included studies that reported on the management of chronic osteomyelitis in long bones using either a planned one-stage or two-stage surgical approach in adult patients. Databases searched included Medline, Embase, Web of Science, CINAHL, HMIC, and AMED, using keywords related to osteomyelitis, long bones, and surgical management. Eligibility criteria focused on adults with chronic osteomyelitis in long bones, with outcomes reported after a minimum follow-up of 12 months. The meta-analysis utilized the random-effects model to pool cure rates. RESULTS: The analysis included 42 studies with a total of 1605 patients. The overall pooled cure rate was 91% (CI 95%) with no significant difference observed between single-stage and two-stage surgeries (X2 = 0.76, P > 0.05). Complications were reported in 26.6% of cases in single-stage procedures and 27.6% in two-stage procedures, with prolonged wound drainage noted as a common issue. Dead space management techniques varied across studies, with antibiotic-loaded calcium sulphate beads used in 30.4% of cases. CONCLUSION: This meta-analysis reveals no significant difference in cure rates between single and two-stage surgical treatments for chronic osteomyelitis in long bones, supporting the efficacy of both approaches. The current treatment strategy should include a combination of debridement, dead space management using local and systematic antibiotics and soft tissue reconstruction if necessary.

P. aeruginosa infection of the ulna, a rare complication after arterial puncture.

Pseudomonas aeruginosa, a Gram-negative bacterium known to induce severe infections, is seldomly reported in scientific literature as a contributor of osteomyelitis. In this case report, a 71-year-old woman exhibited recurring infections and enduring forearm pain. A subsequent MRI revealed osteomyelitis in the distal ulna, linked to an arterial blood gas sample taken months earlier. Despite undergoing multiple extended courses of antibiotic treatment, the patient eventually underwent surgery on her left forearm. Biopsy cultures conclusively confirmed the presence of P. aeruginosa.