Culture-Negative Native Vertebral Osteomyelitis: A Narrative Review of an Underdescribed Condition.

The incidence of culture-negative NVO (CN-NVO) cases is increasing, presenting significant diagnostic and therapeutic challenges due to the inability to isolate causative organisms with conventional microbiological methods. Factors influencing the diagnosis of CN-NVO include prior antimicrobial therapy, low pathogen burden, fastidious or intracellular organisms, technical issues, and non-infectious mimickers. Diagnosis often relies on imaging modalities like magnetic resonance imaging (MRI) and computed tomography (CT)-guided biopsy, though these methods can sometimes fail to yield positive microbiological results. Advanced diagnostic tools, such as polymerase chain reaction (PCR), metagenomic next-generation sequencing (mNGS), and cell-free DNA analysis, may be necessary to identify the pathogen. The causative pathogen cannot be isolated in some patients, among which an empirical antimicrobial therapy should be initiated. This narrative review discusses the management, monitoring, surgical indications, and outcomes for patients with CN-NVO.

Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections.

Background: Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges. Methods: We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Results: In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P < .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result. Conclusions: In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.

Wide variability of the definitions used for native vertebral osteomyelitis: walking the path for a unified diagnostic framework with a meta-epidemiological approach.

BACKGROUND CONTEXT: Native Vertebral Osteomyelitis (NVO) has seen a rise in incidence, yet clinical outcomes remain poor with high relapse rates and significant long-term sequelae. The 2015 IDSA Clinical Practice Guidelines initiated a surge in scholarly activity on NVO, revealing a patchwork of definitions and numerous synonyms used interchangeably for this syndrome. PURPOSE: To systematically summarize these definitions, evaluate their content, distribution over time, and thematic clustering. STUDY DESIGN/SETTING: Meta-epidemiological study with a systematic review of definitions. PATIENTS SAMPLE: An extensive search of multiple databases was conducted, targeting trials and cohort studies dating from 2005 to present, providing a definition for NVO and its synonyms. OUTCOME MEASURES: Analysis of the diagnostic criteria that composed the definitions and the breaking up of the definitions in the possible combinations of diagnostic criteria. METHODS: We pursued a thematic synthesis of the published definitions with Boolean logic, yielding single or multiple definitions per included study. Using 8 predefined diagnostic criteria, we standardized definitions, focusing on the minimum necessary combinations used. Definition components were visualized using Sankey diagrams. RESULTS: The literature search identified 8,460 references, leading to 171 studies reporting on 21,963 patients. Of these, 91.2% were retrospective, 7.6% prospective, and 1.2% RCTs. Most definitions originated from authors, with 29.2% referencing sources. We identified 92 unique combinations of diagnostic criteria across the literature. Thirteen main patterns emerged, with the most common being clinical features with imaging, followed by clinical features combined with imaging and microbiology, and lastly, imaging paired with microbiology. CONCLUSIONS: Our findings underscore the need for a collaborative effort to develop standardized diagnostic criteria. We advocate for a future Delphi consensus among experts to establish a unified diagnostic framework for NVO, emphasizing the core components of clinical features and MRI while incorporating microbiological and histopathological insights to improve both patient outcomes and research advancements.