Abstract Background Prosthetic joint infection (PJI) represents an important complication of total joint arthroplasty, affecting approximately 2% of patients. However, considerable heterogeneity in outcome definitions renders cross-study and clinical comparisons challenging. Methods We performed a meta-epidemiological study and systematic review of cohort studies and randomized controlled trial (RCTs) reporting clear definitions of PJI outcomes. Relevant data regarding outcome definitions of treatment success or failure were extracted and categorized into 7 outcome domains: clinical signs and symptoms, imaging, microbiology, mortality, antibiotics-related, surgical-related, and histology. A network plot was generated to visualize domains combinations. Data on patient-reported outcome measures (PROMs) were also collected. Based on these results, we finally proposed a working definition of PJI core outcome set. Results The literature search identified 7585 references, leading to 461 studies. The majority were retrospective (416/461, 90.2%), with limited representation of prospective studies (37/461, 8.0%) and RCTs (8/461, 1.7%). Outcome reporting was highly heterogeneous, with the clinical criterion being the most frequently used domain, combined with microbiological, surgical, and mortality-related outcomes. In contrast, histopathological, imaging, and antibiotic-related criteria were rarely reported. Thirty-six PROMs were included in only 111 (24.1%) studies, most commonly the Knee Society Score (26%) and Harris Hip Score (23%). Conclusions We showed substantial heterogeneity in PJI outcome definitions, with inconsistent reporting across key domains, limiting comparability and evidence synthesis. Standardized, consensus-based outcomes incorporating patient-reported and antibiotic-related measures are needed, and the proposed core outcome set may support harmonized research and clinical practice aligned with the new PJI definition.
Cephalosporins Versus Non-cephalosporin Antibiotics for Perioperative Prophylaxis in Primary Arthroplasty: A Systematic Review and Meta-Analysis
Abstract Background The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. Methods We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. Results Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46–.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36–1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. Conclusions Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.
Clinical Manifestations, Long-Term Trends, and Risk Factors for Treatment Failure in Native Vertebral Osteomyelitis: A 26-Year Mayo Clinic Experience
Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.
P-99. Defining Success and Failure in Prosthetic Joint Infections: A Meta-epidemiologic Study Towards a Core Outcome Set
Abstract Background A unified definition of prosthetic joint infection outcomes (PJI) is crucial for consistent data, study comparisons, and better care. This study systematically reviews how PJIs outcomes are defined, building on our prior research on native vertebral osteomyelitis and postoperative spinal infection.Figure 1Network plot illustrating the co-occurrence of outcome criteria in prosthetic joint infection studies. Edge thickness reflects the frequency of the co-occurrence of each criterion. Each plot highlights one criterion, namely (1) clinical signs, (2) imaging, (3) microbiology, (4) histopathology, (5) antibiotics-related, (6) surgical-related, (7) mortality. Methods We conducted a comprehensive search of the Cochrane, Embase, Medline, and Scopus databases for studies published after 2005 that clearly defined outcomes for PJI. Eligible studies included randomized controlled trials and cohort studies with a minimum of 10 patients diagnosed with PJI. Our methodology adhered closely to the PRISMA guidelines. Using a saturation approach, we extracted and grouped explicit definitions of PJI outcomes into thematic criteria. A network plot (Figure 1) was used to visualize how frequently these criteria appeared and how they co-occurred across the included studies. Results Out of 7,584 screened studies, 552 (7.3%) met the inclusion criteria. This pilot analysis included 49 randomly selected studies (8,162 patients), mostly retrospective (48/49, 98%), focusing on mixed joint replacements (25/49, 51%), two-stage exchanges (15/49, 31%), or mixed surgeries (24/49, 49%). Only 6/49 (12.2%) applied a society-endorsed definition, and 13/49 (26.5%) cited a reference for their outcome definitions. Overall, 32/49 (65.3%) explicitly defined "success," 35/49 (71.4%) defined "failure," and 16/49 (32.7%) defined both. Most studies (25/49, 51%) had follow-up periods over two years, and 14/49 (28.6%) included patient-reported outcomes, identifying 14 unique PROMs (most commonly UCLA, HHS, and KSS scores). Functional outcomes were assessed in 13/49 (26.5%) studies. We identified 16 distinct outcome criteria across seven categories: clinical signs, microbiology, imaging, histopathology, antibiotics-related, surgical-related, and mortality. Network analysis revealed strong links among clinical signs, microbiology, surgical factors, mortality, and imaging. Conclusion Our pilot study found major variation in PJI outcome definitions, with few standardized criteria. A consensus-driven approach is needed to strengthen evidence synthesis and advance patient care in PJI. Disclosures All Authors: No reported disclosures
Abstract Background The increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently. 2020 PRISMA flow diagram Sankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors. Methods Following PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI) Results From an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2). Conclusion There was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems. Disclosures Jeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)
INFECTIVE ENDOCARDITIS MEETS NATIVE VERTEBRAL OSTEOMYELITIS: A MORTALITY PERSPECTIVE
Aims Native vertebral osteomyelitis (NVO) and infective endocarditis (IE) are increasingly seen as interconnected conditions, sharing similar risk factors — such as advanced age and immunosuppression — and overlapping microbial profiles, notably Staphylococcus aureus and streptococci. When these infections occur together, they present distinct challenges in diagnosis and treatment, which can obscure clear outcomes and mortality estimates. Therefore, we aimed to systematically assess the combined mortality associated with concurrent NVO and IE and to detail the clinical characteristics of affected patients. Methods We conducted a systematic review following the PRISMA framework, searching MEDLINE, Embase, the Cochrane Library, and Scopus for relevant studies published between 1970 and October 2023. Studies included were those reporting mortality outcomes for at least ten adult patients with both NVO and IE. Two independent reviewers screened the literature, extracted data, and evaluated study quality using a modified Newcastle-Ottawa Scale. We then performed a random-effects meta-analysis to pool in-hospital, 1-month, 1-year, and 3-year mortality rates. Results A total of 16 studies (12 retrospective, 3 prospective, and 1 mixed design) involving 641 patients (mean age 67.1 years) with concomitant NVO and IE were included. The pooled in-hospital mortality rate was 10.0% (95% CI: 5.2–14.7%), with mortality rates of 5.6% (95% CI: 2.2–9.0%) at 1 month, 12.1% (95% CI: 5.3–18.8%) at 1 year, and 14.5% (95% CI: 4.3–24.8%) at 3 years. There was significant heterogeneity among studies (I² ranging from 46% to 86%). Common comorbidities included diabetes (24.6%), renal failure (17.3%), and immunosuppression (11.1%). The predominant pathogens identified were streptococci (31.3%), S. aureus (27.3%), and enterococci (13.7%). Approximately 40.6% of patients underwent surgical intervention, though its effect on mortality remains inconclusive. Overall, the certainty of the estimates was limited by imprecision and impossibility of perform subgroup analysis. Conclusion The coexistence of NVO and IE is associated with significant mortality, emphasizing the need for earlier diagnosis, coordinated multidisciplinary management, and standardized treatment protocols. Future prospective, high-quality studies are crucial to determine optimal diagnostic and surgical strategies for managing this complex clinical scenario.
POSTOPERATIVE SPINAL INFECTIONS: THE CHALLENGE OF INCONSISTENT DEFINITIONS AND THE PATH TOWARDS CONSENSUS
Background The rising number of spinal surgeries has been paralleled by an increase in postoperative spine infections (PSIs), now identified as the third most common surgical complication. The absence of a standardized PSI definition complicates clinical management and research. This meta-epidemiological study was conducted to establish clear diagnostic criteria to aid clinicians and researchers in consistently identifying and reporting PSIs. Methods In accordance with PRISMA guidelines, a comprehensive literature search was performed using Ovid MEDLINE on March 14, 2024, by a medical librarian. Studies were considered eligible if they reported clear diagnostic definitions of PSI in at least ten adult patients. The primary objective was to review existing PSI diagnostic criteria and classify them into thematic clusters. We developed standardized diagnostic combinations based on 13 predefined criteria sourced from clinical practice guidelines and previous research (see Table 1). Results From an initial pool of 1,466 studies, 101 were included. The vast majority were retrospective (91/101, 92.1%), with most studies (77/101, 76.2%) utilizing established criteria, such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined these predefined criteria with additional detailed descriptions. Among studies using independent definitions, clinical signs and symptoms were the most commonly reported criteria (13/24, 54.2). The criteria were grouped into clinical, microbiological, and radiological categories, with most studies employing clinical criteria either alone or alongside microbiological or imaging findings (Figure 1). Conclusion These findings highlight the urgent need for a standardized definition of PSI that integrates clinical, microbiological, and radiological elements. Implementing such a unified diagnostic framework could enhance accuracy, address limitations related to hardware complications, wound drainage interpretation, and imaging ambiguities, and improve current surveillance practices. For any figures or tables, please contact the authors directly.
Consequences of Delaying Surgical Intervention in Patients With Native Joint Septic Arthritis
Abstract Background Although recent guidance recommends early surgical debridement for native joint septic arthritis (NJSA), supporting data, particularly on long-term outcomes, remains scarce. Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NJSA who underwent surgery across Mayo Clinic campuses between 2012 and 2021. Clinical outcomes at 1 year were assessed using a 9-level Desirability of Outcome Ranking (DOOR) scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery. Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: < 1, 1–2, or ≥3 days. Results Among 268 patients, 30% underwent surgery <1 day from admission, 47% in 1–2 days, and 24% in ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34%. In unadjusted analyses, longer surgical delay was significantly associated with higher (worse) DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; P = .026), increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; P = .019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; P = .007). Even after adjusting for age and Charlson comorbidity index, the association between surgical delay and treatment failure remained significant (HR: 1.5; 95% CI, 1.1–2.0; P = .016). Conclusions The finding that delayed surgical intervention is associated with an increased risk of treatment failure reinforces current expert recommendations for timely surgical management in NJSA.