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Clinical Advances in Orthopedic Infections

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Orthopedics".

Deadline for manuscript submissions: closed (20 November 2025) | Viewed by 7740

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Dr. Hyonmin Choe

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Department of Orthopaedic Surgery, Yokohama City University, Yokohama, Japan
Interests: orthopedic surgery; robot surgery; orthopedic infections; periprosthetic joint infection; surgical site infection
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Special Issue Information

Dear Colleagues,

The complexity of orthopedic infections and their profound impact on patient outcomes has been widely recognized over recent decades. We are honored to present this Special Issue, which provides a platform for sharing the knowledge, experiences, and latest advancements from leading experts in the field of orthopedic infections.

Orthopedic infections significantly impair the quality of life of patients and introduce complex challenges in therapy. Thanks to recent research and technological progress, there have been notable advancements in the prevention, diagnosis, and treatment of these infections. This Special Issue explores such advancements, addressing the current challenges and envisioning future possibilities in the management of orthopedic infections. By connecting clinical insights with scientific breakthroughs, our objective is to illuminate the path forward in the management of orthopedic infections.

We anticipate that this Special Issue will act as a pivotal force in enriching our understanding of orthopedic infections and fostering discussions aimed at establishing best practices in patient care.

Dr. Hyonmin Choe
Guest Editor

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Keywords

orthopedic surgery
orthopedic infections
periprosthetic joint infection
surgical site infection
infection management

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Related Special Issue

Clinical Advances in Orthopedic Infections: 2nd Edition in Journal of Clinical Medicine

Published Papers (7 papers)

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11 pages, 1391 KB

Open AccessArticle

Delta Neutrophil Index in Suspected Septic Arthritis: A Diagnostic Accuracy Study

by Hüseyin Emre Tepedelenlioğlu, Hilmi Alkan, Tural Talıblı, Ünal Erkanov Hüseyinov, Ferid Abdulaliyev, Erkan Akgün and Vedat Biçici

J. Clin. Med. 2026, 15(2), 840; https://doi.org/10.3390/jcm15020840 - 20 Jan 2026

Viewed by 355

Abstract

Background/Objectives: Septic arthritis of native joints is an orthopedic emergency in which rapid discrimination from non-infectious arthritis is crucial. Because cartilage damage can occur within hours, urgent irrigation and debridement are often pursued on an emergency basis (ideally within the first 6–8 h) of presentation, underscoring the need for rapidly available biomarkers. The delta neutrophil index (DNI) quantifies circulating immature granulocytes and may complement conventional inflammatory biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and procalcitonin (PCT). We evaluated the diagnostic performance of DNI for native-joint septic arthritis against both microbiologic and clinical reference standards. Methods: We retrospectively analyzed 85 adults who underwent surgical irrigation and debridement for suspected native joint septic arthritis at a tertiary center. Serum CRP, ESR, WBC, DNI, and PCT (available in 67 patients) were recorded together with synovial leukocyte counts. Infection status was defined using either positive synovial culture (microbiologic reference) or clinical adjudication according to the Guideline for management of septic arthritis in native joints (SANJO). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC); exploratory cut-offs were identified by the Youden index, and pairwise AUCs were compared using DeLong’s test. Results: Synovial leukocyte analysis was highly sensitive but poorly specific (sensitivity 92.9%, specificity 10.3%). Against culture, DNI showed the highest discrimination (AUC = 0.914), exceeding CRP (0.687), ESR (0.643), WBC (0.648), and PCT (0.697); DeLong ΔAUC vs. CRP 0.227 (p < 0.001), ESR 0.270 (p < 0.001), WBC 0.266 (p < 0.001), PCT 0.227 (p = 0.001). At pre-specified cut-offs, DNI showed the most balanced sensitivity/specificity (94.3%/84.0%), corresponding to a negative predictive value (NPV) of 95.5% (42/44) and a positive predictive value (PPV) of 80.5% (33/41) against culture in this cohort. Against clinical infection, DNI outperformed others (AUC:0.921; ΔAUC vs. CRP = 0.204, ESR = 0.343, WBC = 0.244, PCT = 0.295; all p < 0.001). As a rule-in threshold, DNI ≥ 0.6 yielded a specificity of 100% with a sensitivity of 73.2%. In culture-negative patients (infected n = 21, uninfected n = 29), DNI remained discriminatory (AUC 0.80, p < 0.001), whereas other biomarkers were not. Conclusions: DNI demonstrated superior diagnostic accuracy compared with conventional inflammatory biomarkers. As a rapid parameter available with the initial complete blood count, DNI may support early risk stratification and rule-in decisions within the first hours of presentation; however, it should be used as a supplementary indicator alongside synovial fluid analysis and clinical assessment rather than as a stand-alone diagnostic tool. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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13 pages, 1840 KB

Open AccessArticle

Early Clinical Experience with Silver-Ion Doped Synthetic Bone Grafts for the Treatment of Chronic Bone Infections: A Retrospective Study

by Bünyamin Yücel, Aydan Ayşe Köse and Nusret Köse

J. Clin. Med. 2026, 15(1), 29; https://doi.org/10.3390/jcm15010029 - 20 Dec 2025

Viewed by 406

Abstract

Background/Objectives: Chronic bone infections require local antimicrobial delivery to achieve high drug concentrations while limiting systemic toxicity. Silver ion-doped calcium phosphate synthetic bone grafts have been proposed as carriers for local antimicrobial release. This study aimed to evaluate the efficacy and safety of a silver ion-doped synthetic bone graft in patients with chronic osteomyelitis, infected nonunion, or implant-related bone infection. Methods: This retrospective cohort included 12 adults who underwent surgery for chronic osteomyelitis or implant-associated infection. All patients received thorough debridement, removal of infected implants when present, and filling of bone defects with a silver ion-doped calcium phosphate graft. The median age was 38 years, and follow-up was 12 months. Clinical and radiographic outcomes, liver and kidney function tests, and blood silver levels were assessed pre- and postoperatively. Results: Infection eradication was achieved in 11 of 12 patients (90%) at 12 months. Functional recovery, defined as return to normal daily activities, occurred within 3–5 months. Bone union was observed in all but one patient within 3–6 months, and no graft resorption was detected at one year. No significant differences in liver or kidney function tests were found compared with the control group (p > 0.05), and blood silver levels remained within normal limits. Conclusions: At 12-month follow-up, silver ion-doped synthetic bone grafts showed encouraging safety and efficacy in the treatment of chronic osteomyelitis. These findings suggest that silver-doped grafts may represent a useful option for one-stage treatment of osteomyelitis. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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13 pages, 2862 KB

Open AccessArticle

Treatment of Primary Cervical Spine Infections: A Single-Center Analysis of the Management of 59 Patients over Three Decades

by Myung-Jin Sung and Sung-Kyu Kim

J. Clin. Med. 2025, 14(23), 8446; https://doi.org/10.3390/jcm14238446 - 28 Nov 2025

Viewed by 503

Abstract

Background: Primary cervical spine infection is a rare but rapidly progressive disease that can cause early neurological damage, leading to increased morbidity and mortality. Despite its rising incidence, optimal treatment remains controversial. This study compared clinical, hematological, microbiological, and radiological outcomes among such patients treated with different methods. Methods: This retrospective comparative study is a secondary analysis of a previously reported cohort of 59 patients with primary cervical spine infection between 1992 and 2018 at a single institution. Patients were stratified into conservative (Group C, n = 14), surgery with instrumentation (Group S + I, n = 32), and surgery without instrumentation (Group S, n = 13) groups. Outcome measures included neurological status, antibiotic duration, hematological markers, radiological parameters (segmental angle, C2–C7 angle, segmental height, fusion rate), and complications. Results: The mean age and follow-up period were 61.4 years and 19.4 months, respectively. Group S + I demonstrated significantly better neurological outcomes at the last follow-up (p = 0.047) and shorter antibiotic treatment duration (p < 0.001). Radiological outcomes were superior in Group S + I, with greater improvements in segmental angle (p < 0.001), C2-C7 angle (p < 0.001), mean segmental height (p < 0.001), and fusion rate (84.4% vs. 14.3% and 46.2% in Group C and Group S, respectively; p < 0.001). Group S had significantly higher complication (46.2%, p = 0.011) and mortality (30.8%, p = 0.001). Hematological and microbiological results were not significantly different among groups. Conclusions: Surgical debridement with anterior instrumentation provided superior outcomes compared with conservative treatment or surgery without instrumentation. Early surgery with appropriate stabilization should be considered to optimize prognosis and minimize complications. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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13 pages, 667 KB

Open AccessArticle

Evaluation of the Diagnostic Accuracy of Serum Albumin and Globulin in Pyogenic Spondylitis

by Hideo Mitsui, Hyonmin Choe, Masashi Shimoda, Hironori Yamane, Yuta Hieda, Koki Abe, Yohei Ito, Hiroyuki Ike, Ken Kumagai, Naomi Kobayashi and Yutaka Inaba

J. Clin. Med. 2025, 14(17), 6001; https://doi.org/10.3390/jcm14176001 - 25 Aug 2025

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Background: Serum markers are commonly used to diagnose bone and joint infections; however, their accuracy for diagnosing pyogenic spondylitis remains unproven. This study aimed to validate the diagnostic accuracy of inflammatory, nutritional, and immunological serum markers for spinal infections and identify the most effective combinations. Methods: The retrospective cohort study analyzed 656 patients who visited the hospital for spinal diseases between 1 January 2004 and 31 March 2021; a total of 76 were diagnosed with pyogenic spondylitis. Blood samples were analyzed for serum albumin (Alb), total protein (TP), globulin (Glb), C-reactive protein (CRP), platelet count, white blood cell count, neutrophil count, lymphocyte count, and monocyte count. Combination markers, including albumin–globulin ratio (AGR), CRP–albumin ratio (CAR), CRP–AGR (CAGR), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), were also evaluated. Receiver operating characteristic curves were used to determine each marker’s diagnostic performance. Furthermore, multivariate analysis was performed to examine the odds ratios. Results: Patients with pyogenic spondylitis showed significantly different levels in Alb (p < 0.0001), Glb (p < 0.0001), CRP (p < 0.0001), platelet count (p < 0.0001), WBC count (p < 0.0006), neutrophil count (p = 0.0019), lymphocyte count (p = 0.0085), AGR (p < 0.0001), CAR (p < 0.0001), CAGR (p < 0.0001), NLR (p < 0.0001), and PLR (p < 0.0001). CRP (AUC = 0.80) showed good diagnostic accuracy, while combination markers CAR (AUC = 0.82) and CAGR (AUC = 0.83) had the highest areas under the curve (AUC). Multivariate analysis indicated that decreased age and the presence of comorbidities (including chronic kidney disease, chronic liver disease, malignancy, or diabetes), were independent predictors of early pyogenic spondylitis (OR_age = 0.93, OR_comorbidities = 16.98, p_age = 0.0005, and p_comorbidities = 0.0001). In patients with low-inflammatory pyogenic spondylitis, significant differences were observed in TP (p = 0.0293), Glb (p = 0.0012), CRP (p = 0.0023), platelet count (p = 0.0108), AGR (p = 0.0044), CAR (p = 0.0006), CAGR (p = 0.0004), PLR (p = 0.0192), and NLR (p = 0.0027), with CAGR showing the highest AUC (AUC = 0.70) among them. Conclusions: Serum combination markers (AGR, CAGR, CAR, PLR, and NLR) showed diagnostic value for pyogenic spondylitis, with CAGR achieving the highest accuracy. In low-inflammatory pyogenic spondylitis patients (CRP ≤ 1.0 mg/dL), these markers may aid diagnosis. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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10 pages, 1209 KB

Open AccessArticle

Feasibility and Potential Clinical Ramifications of Using Bacteriophage Therapy for S. aureus Necrotizing Fasciitis

by James B. Doub, Dakarai Dunbar, Sara Jain, Maggie Manchester, Lila Berle, Janvi Madhiwala, Bradley Anderson, Riva Malick, Max Jacobs and Kenneth L. Urish

J. Clin. Med. 2025, 14(16), 5609; https://doi.org/10.3390/jcm14165609 - 8 Aug 2025

Cited by 1 | Viewed by 830

Abstract

Background: Staphylococcus aureus necrotizing fasciitis is a life-threatening infection requiring aggressive surgical and medical management. Despite these interventions, tremendous morbidity and mortality occur. Thus, novel agents are needed to reduce these negative outcomes. Consequently, the aims of this translational study were to evaluate the feasibility of using bacteriophages and the potential clinical ramifications of using bacteriophages in treatment of S. aureus necrotizing fasciitis. Methods: Necrotizing fasciitis clinical isolates (n = 6) were tested against different Staphylococcal bacteriophages (n = 4) to assess for activity. After exposure to bacteriophages that had growth inhibition for more than 16 h, the ability of S. aureus to change phenotypic expression of numerous enzymes was evaluated, and the ability to reduce bacterial virulence was measured with the Caenorhabditis elegans assay. Results: Staphylococcal myoviridae bacteriophages were able to lyse most clinical isolates (83%). Interestingly, after exposure to myoviridae bacteriophages, S. aureus isolates had no expression of hemolysin, secreted coagulase, or lecthinase, or the ability to ferment mannitol. These same bacteriophages also caused statistically significant decreases in bacterial virulence (p < 0.05). Neither findings were observed for bacteriophages of the podoviridae family. Conclusions: To use bacteriophages for S. aureus necrotizing fasciitis, cocktails of Staphylococcal myoviridae are likely needed to allow for broad host ranges, mitigating the need for in vitro sensitivity testing. Moreover, Staphylococcal myoviridae have the potential to reduce specific enzyme expression and global virulence of residual S. aureus. Thus, bacteriophages may aid in reducing necrotizing fasciitis morbidity by not only lysing S. aureus but also by reducing S. aureus virulence. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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12 pages, 2139 KB

Open AccessArticle

Biofilm Growth on Different Materials Used in Contemporary Femoral Head Prosthesis: An In Vitro Study

by Yonggyun Moon, Jaeyoung Hong, Sookyung Choi, Hyoungtae Kim, Hong Moon Sohn and Suenghwan Jo

J. Clin. Med. 2025, 14(5), 1722; https://doi.org/10.3390/jcm14051722 - 4 Mar 2025

Viewed by 1533

Abstract

Background/Objectives: Periprosthetic joint infection (PJI) primarily results from bacterial biofilms adhering to prosthetic surfaces, making treatment challenging without prosthesis removal. This in vitro study aims to investigate whether the materials used in contemporary femoral head prosthesis influences bacterial biofilm development. Methods: Femoral head prostheses made of three different materials—cobalt–chrome, oxinium, and ceramic—were inoculated with either Staphylococcus aureus or Pseudomonas aeruginosa in separate experiments, with each pathogen tested independently. The samples were cultured under shaking conditions at 37 °C for 96 h to promote biofilm formation. Scanning electron microscopy (SEM) was used to confirm the presence of biofilms, and adherent biofilms were quantified by counting colony-forming units (CFUs) after sonication. Additionally, crystal violet staining was performed to assess biofilm distribution on the femoral head surfaces. Statistical analyses compared CFU counts across the different materials. Results: The mean CFU counts for S. aureus were 7.6 × 10⁵ ± 9.7 × 10⁴ for cobalt–chrome, 6.9 × 10⁵ ± 3.6 × 10⁵ for oxinium, and 1.1 × 10⁶ ± 3.0 × 10⁵ for ceramic femoral head prostheses. For P. aeruginosa, the CFU counts were 2.3 × 10⁶ ± 7.2 × 10⁵, 3.7 × 10⁶ ± 2.5 × 10⁶, and 2.2 × 10⁶ ± 8.9 × 10⁵, respectively. Regardless of the bacterial strain, differences among the three materials were within one log range, and no statistical significance was observed. While biofilms were confirmed using SEM, limited adherence was observed on the bearing surface, with the biofilm predominantly localized in the taper hole. Conclusions: The findings suggest that the material used in contemporary femoral head prostheses has minimal impact on bacterial biofilm formation. Surgeons’ choice of femoral head prosthesis material should base their material selection on factors other than PJI prevention. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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10 pages, 785 KB

Open AccessCase Report

Neisseria sicca Vertebral Osteomyelitis: A Case Report and Literature Review

by Natasha Priya Dyal, Robert Orenstein and Sandhya Rani Nagarakanti

J. Clin. Med. 2024, 13(23), 7241; https://doi.org/10.3390/jcm13237241 - 28 Nov 2024

Cited by 2 | Viewed by 2124

Abstract

Background: Culture-negative vertebral osteomyelitis presents a significant diagnostic challenge. Neisseria sicca (N. sicca) is a typically benign commensal organism of the upper respiratory tract that rarely causes invasive infections, warranting cautious interpretation if isolated in a single positive culture. This case study details a 62-year-old male diagnosed with vertebral osteomyelitis caused by N. sicca, examining diagnostic challenges, treatment, and outcomes. Methods: We conducted a comprehensive search on MEDLINE using the keywords “Neisseria sicca”, “osteomyelitis”, and “diskitis”. An additional search excluding N. gonorrhea and N. meningitidis was also performed, revealing a total of four cases of N. sicca osteomyelitis in the literature. Results: A 62-year-old male with a history of hypertension, type 2 diabetes, atrial fibrillation, and previous L5-S1 spinal fusion presented with fever and back pain in May 2023. Initial imaging revealed T8-T9 vertebral osteomyelitis. Despite a six-week course of IV daptomycin, his symptoms worsened, prompting further evaluation. A CT-guided biopsy with comprehensive testing, including histopathology and microbial cultures, initially identified N. sicca. Due to its rarity, additional biopsies were conducted, confirming the infection. IV ceftriaxone was initiated, leading to significant pain improvement, and a subsequent MRI showed near resolution. The patient transitioned to oral cefuroxime, with follow-up confirming complete infection resolution by December 2023. Conclusions: This case underscores the importance of a structured diagnostic approach in culture-negative vertebral osteomyelitis to differentiate between commensal contamination and true infection. Repeated positive cultures of N. sicca from a sterile site confirmed its role as the causative agent. Early identification and targeted antibiotic therapy are critical to improving outcomes in rare cases of N. sicca vertebral osteomyelitis. Full article

(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)

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