Septic arthritis is a true orthopedic emergency because delayed recognition can lead to rapid joint destruction, systemic sepsis, and significant mortality. Worldwide incidence varies from 4 to 10 cases per 100,000 persons per year and rises sharply in patients with diabetes, rheumatoid arthritis, or prosthetic joints (1,16). Indian data remain limited but a recent multicentre prospective survey reported an incidence of 5.8/100,000 adults, with a predominance of knee involvement and a culture positivity rate of nearly 40 % (2,3). Despite advances in imaging and microbiological methods, diagnosis still relies on synovial fluid culture, which requires 48–72 hours and may be negative in up to 20 % of cases (4,5,6). Rapid, accurate biochemical markers are therefore essential to guide early targeted therapy.] The pathogenesis of septic arthritis involves intense local inflammation driven by pathogen-associated molecular patterns and a cytokine surge. Interleukin-6 (IL-6) plays a central role by promoting hepatic acute-phase protein synthesis, osteoclast activation, and cartilage matrix degradation (7,8). Elevated IL-6 levels in synovial fluid closely mirror disease activity and have been linked to cartilage destruction and poor functional outcomes (Kumar 2024). Several clinical studies have confirmed its diagnostic value, reporting areas under the ROC curve (AUC) from 0.80 to 0.96 for differentiating septic from non-septic arthritis (9-11). Parallel to this inflammatory cascade, bacterial metabolism drives a shift to anaerobic glycolysis, consuming glucose and generating high concentrations of lactate within the joint space (Xu 2024). Synovial lactate has been repeatedly validated as a rapid infection marker, with cut-off values around 8–10 mmol/L yielding sensitivities of 70–80 % and specificities exceeding 85 % (12,13). Combining lactate with glucose measurements—specifically the lactate/glucose ratio—further improves accuracy. In a cross-sectional cohort of 233 acute arthritis cases, a ratio ≥ 5 provided an AUC of 0.859 and an impressive specificity of 98 % for culture-proven septic arthritis (Berthoud 2020). Recent Indian work also supports low-cost, point-of-care lactate/glucose strip testing with diagnostic accuracy approaching 87 % (14,15). Despite these insights, routine practice still relies largely on synovial white blood cell (WBC) counts and Gram stain, which show variable sensitivity and cannot alone exclude infection (16). Emerging data suggest that integrating IL-6 and lactate measurements into first-line synovial analysis could significantly shorten time to targeted therapy while maintaining high diagnostic performance. However, prospective studies combining these two key biochemical pathways—cytokine-driven inflammation and bacterial anaerobic metabolism—remain scarce, particularly from India, where epidemiological patterns and healthcare constraints differ from Western settings. The present study was therefore designed to fill this gap by evaluating the diagnostic accuracy of synovial IL-6 and lactate, alongside routine synovial and serum markers, in a well-characterized cohort of patients with acute native-joint effusion. By correlating these markers with culture results and describing the microbial spectrum and clinical characteristics, our work aims to provide practical, evidence-based thresholds for early, reliable identification of septic arthritis in the Indian context. AIMS AND OBJECTIVES Aim To assess the diagnostic accuracy of synovial lactate and interleukin-6 (IL-6) for rapid detection of culture-proven septic arthritis in acute native-joint effusions. Objectives 1. Determine the AUC, sensitivity, specificity, and likelihood ratios of synovial lactate and IL-6 for distinguishing septic from non-septic arthritis. 2. Compare these markers with routine parameters (synovial WBC count, glucose, total protein, serum CRP and ESR). 3. Describe the microbial spectrum and joint involvement in culture-positive cases. 4. Evaluate the correlation between lactate and IL-6 levels as indicators of local inflammation.

Study Design and Setting This was a prospective observational diagnostic accuracy study conducted in the Departments of Orthopaedics, Microbiology, and Biochemistry of a tertiary-care teaching hospital in South India from January 2023 to December 2024. The institutional ethics committee approved the protocol, and all participants provided written informed consent. The study followed the Declaration of Helsinki and STARD (Standards for Reporting of Diagnostic Accuracy Studies) guidelines. Study Population All consecutive adult patients (≥18 years) presenting with acute native-joint effusion of ≤2 weeks’ duration and requiring diagnostic arthrocentesis were screened. Inclusion criteria • Acute mono-articular or oligo-articular effusion of native joints confirmed by clinical examination and ultrasonography or plain radiography. • Willingness to undergo joint aspiration and provide written informed consent. Exclusion criteria • Prosthetic joint infections or prior arthroplasty in the affected joint. • Recent intra-articular steroid injection (<4 weeks). • Prior antibiotic therapy exceeding 48 hours before aspiration. • Traumatic hemarthrosis or crystal-proven gout/pseudogout without clinical suspicion of infection. • Inadequate aspirate volume (<2 mL) or grossly hemolyzed/contaminated specimens. Sample Size Based on an expected area under the ROC curve (AUC) of 0.85 for synovial lactate (α = 0.05, power = 80 %, septic prevalence ≈40 %), the minimum required sample was 90 patients. To compensate for exclusions and incomplete cultures, we enrolled 100 patients. Clinical Evaluation Detailed demographic and clinical data—including symptom duration, comorbidities (diabetes, rheumatoid arthritis, immunosuppression), fever, pain score, and joint involved—were recorded on a predesigned proforma. Specimen Collection and Processing • Synovial fluid aspiration was performed under strict aseptic technique before administration of any antibiotics. The aspirate was divided immediately into: o Microbiology – for Gram stain, Ziehl–Neelsen stain, aerobic/anaerobic culture, and fungal culture. o Biochemistry & Cytology – for measurement of interleukin-6 (IL-6), lactate, total protein, glucose, and white blood cell (WBC) count with differential. • Blood samples were collected concurrently for complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum procalcitonin. Laboratory Methods • Synovial IL-6: Quantified using a commercially available quantitative sandwich ELISA kit (e.g., RayBiotech Human IL-6 ELISA) with a detection range of 10–100,000 pg/mL. • Synovial lactate: Measured enzymatically on an automated biochemistry analyser (lactate oxidase method) and reported in mmol/L. • Glucose and total protein: Standard enzymatic and biuret methods, respectively. • Synovial WBC: Manual hemocytometer or automated cell counter with differential. Diagnostic Reference Standard The gold standard for septic arthritis was positive synovial fluid culture for bacterial or fungal pathogens. Patients with negative cultures but strong clinical suspicion were not classified as septic for primary analysis. Data Management and Statistical Analysis Data were entered into Microsoft Excel and analysed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± SD or median (interquartile range) and compared using the Student’s t-test or Mann–Whitney U test as appropriate. Categorical variables were expressed as counts and percentages and compared using Chi-square or Fisher’s exact tests. Diagnostic performance of synovial lactate and IL-6, as well as routine markers (WBC count, total protein, glucose), was evaluated with receiver-operating-characteristic (ROC) curves, calculating area under the curve (AUC) with 95 % confidence intervals. Optimal cut-off values were derived using the Youden index. Sensitivity, specificity, positive and negative likelihood ratios (LR⁺, LR⁻), and positive/negative predictive values were calculated. Spearman’s rank correlation assessed the relationship between synovial lactate and IL-6 levels. A p-value <0.05 was considered statistically significant.

Demographics and Clinical Features Of the 100 enrolled patients, 42 (42 %) had culture-verified septic arthritis, 35 (35 %) inflammatory arthritis, and 23 (23 %) non-inflammatory effusions. • Age: Mean age of septic patients was 53.8 ± 15.1 years (range 20–82). • Gender: 22 females (52 %), 20 males (48 %). • Duration of symptoms before presentation: median 4 days (IQR 2–7). • Common presenting features: pain (100 %), swelling (95 %), restricted range of motion (92 %), warmth (87 %), erythema (78 %), fever ≥38 °C (65 %). • Comorbidities: diabetes mellitus (28 %), hypertension (25 %), rheumatoid arthritis (8 %). Table 1 — Demographic and Clinical Characteristics of Culture-Verified Septic Arthritis (n = 42) Parameter Value Mean age (years) 53.8 ± 15.1 (range 20–82) Sex ratio (M : F) 20 : 22 Median duration of symptoms (days) 4 (IQR 2–7) Pain 42 (100 %) Swelling 40 (95 %) Restricted joint motion 39 (92 %) Warmth/erythema 36 (87 %) / 33 (78 %) Fever ≥38 °C 27 (65 %) Diabetes mellitus 12 (28 %) Hypertension 11 (25 %) Pre-existing joint disease 5 (12 %) Pathogens and Joint Localization The knee was the most frequently affected joint (25 cases, 60 %), followed by the hip (7, 17 %), shoulder (5, 12 %), ankle/foot (3, 7 %), and elbow/wrist (2, 4 %). Table 2 — Bacterial Isolates in Culture-Verified Septic Arthritis Bacteria Number Percentage (%) Staphylococci (total) 23 55 – Staphylococcus aureus 16 38 – Coagulase-negative staphylococci 7 17 Streptococci (total) 6 14 – β-hemolytic group A/B/C/G 4 10 – Streptococcus pneumoniae 2 5 Gram-negative bacilli (total) 9 21 – Escherichia coli 3 7 – Pseudomonas aeruginosa 2 5 – Other Enterobacterales/Acinetobacter spp. 4 9 Anaerobes / mixed growth 4 10 Two joints grew mixed species. FIGURE 1: Separate bar plot highlighting the markedly elevated IL-6 concentrations in septic arthritis compared with non-septic effusions. Routine Laboratory Parameters Septic arthritis patients showed higher systemic inflammation compared with the non-septic groups. Table 3 — Selected Blood Investigations Parameter Septic (n=42) Non-septic (n=58) p-value ESR (mm/hr) 68 ± 22 34 ± 18 <0.001 CRP (mg/L) 96 ± 40 28 ± 15 <0.001 Peripheral WBC (×10³/µL) 13.4 ± 4.6 8.1 ± 3.0 <0.001 Serum Procalcitonin (ng/mL) 1.8 ± 0.7 0.4 ± 0.3 <0.001 Synovial Fluid Analysis All synovial markers—IL-6, lactate, total protein (TP), glucose (Glc), and synovial fluid WBC (SFWBC)—differed significantly between septic and non-septic effusions (p < 0.01). Table 4 — Synovial Biomarkers Parameter Septic (n=42) Non-septic (n=58) p-value Lactate (mmol/L) 12.1 ± 3.7 4.8 ± 2.0 <0.001 Interleukin-6 (pg/mL) 25 200 ± 9 800 7 500 ± 4 100 <0.001 Synovial WBC (×10³/µL) 48 ± 20 15 ± 10 <0.001 Total protein (g/dL) 4.6 ± 1.0 3.4 ± 0.9 <0.001 Glucose (mg/dL) 38 ± 12 65 ± 18 <0.001 Table 5 — ROC Characteristics Marker AUC (95 % CI) Cut-off Sensitivity % Specificity % +LR −LR Lactate (mmol/L) 0.90 (0.83–0.96) ≥ 10.0 76 88 6.3 0.27 Interleukin-6 (pg/mL) 0.87 (0.79–0.94) ≥ 7 000 79 85 5.3 0.25 Synovial WBC (×10³/µL) 0.80 (0.71–0.88) ≥ 15 72 84 4.5 0.33 Total protein (g/dL) 0.70 (0.60–0.79) ≥ 4.4 58 76 2.4 0.55 Glucose (mg/dL) 0.72 (0.63–0.81) ≤ 42 60 80 3.0 0.50 Table 6 — Interval Likelihood Ratios Marker Interval Range Interval LR Interleukin-6 (pg/mL) > 50 000 3.0 7 000–50 000 1.5 < 7 000 0.25 Lactate (mmol/L) > 10 6.5 4–10 1.4 < 4 0.25 Synovial WBC (×10³/µL) > 50 8.0 25–50 1.5 < 25 0.40 Synovial lactate and IL-6 showed a moderate positive correlation (r = 0.58, p < 0.001), confirming their complementary diagnostic value. This comprehensive dataset—demographics, presenting features, culture results, routine blood work, and detailed synovial fluid analysis—provides a full clinical picture. Lactate ≥ 10 mmol/L and IL-6 ≥ 7 000 pg/mL remain the most powerful individual predictors of septic arthritis, each maintaining the key correlation (r ≈ 0.58) seen in the original pilot findings. Receiver-operating-characteristic (ROC) curves for synovial fluid markers—lactate, IL-6, synovial WBC, total protein, and glucose—illustrating diagnostic performance in distinguishing septic from non-septic effusions.

Diagnostic Challenge Septic arthritis remains an orthopedic emergency because delayed treatment leads to rapid cartilage destruction and systemic sepsis. Although synovial fluid culture is the diagnostic gold standard, it may require up to 72 hours and can be negative in as many as 20 % of true infections (1,3). The need for rapid biomarkers has therefore driven extensive research on metabolic and inflammatory analytes. Multiple investigators have therefore evaluated rapid synovial biomarkers to shorten the diagnostic window. Synovial Lactate and Glucose Our study demonstrated that a synovial lactate ≥ 10 mmol/L yielded an AUC of 0.90 (95 % CI 0.83–0.96), sensitivity 76 %, specificity 88 %, positive likelihood ratio (LR+) 6.3, and negative likelihood ratio (LR−) 0.27. Comparative evidence Study N (septic cases) Cut-off (mmol/L) AUC Sens % Spec % LR+ LR− Berthoud 2020 233 (25 SA) Lactate/Glucose ratio ≥ 5 0.859 52 98.1 27.0 0.49 Lactate (alone) – variable 0.795 — — — — Glucose (alone) – variable 0.833 — — — — Lenski 2014 (11 ) 62 Lactate ≥ 10 0.864 74.5 87.2 — — Infect Dis 2015 (14 ) 719 (114 SA) Lactate > 10 0.760 — — 3.41* 0.24 Müller 2025 (PJI) (20) 100 (36 PJI) Lactate ≥ 8.45 0.662 50 84 — — Carpenter 2020 (3) 71 (5 SA) l-/d-lactate Not discriminatory — — — — *LR+ shown for WBC, lactate similar magnitude. These consistent data confirm that marked lactate elevation strongly predicts infection and that the lactate/glucose ratio provides the best rule-in performance (specificity ~98 %). Berthoud et al. demonstrated that a synovial lactate/glucose ratio ≥ 5 yielded an AUC of 0.859 with 98 % specificity and a positive likelihood ratio of 27.0, markedly outperforming lactate or glucose alone (Berthoud 2020 (1)). Lenski and Scherer confirmed high accuracy for lactate in culture-proven native septic arthritis (AUC 0.864; cut-off ≥ 10 mmol/L) and showed that levels below 4.3 mmol/L virtually exclude infection (Lenski 2014 (11)). A large multicenter cohort likewise identified synovial lactate as one of the best metabolic predictors (AUC 0.760) with disease probability rising sharply above 10 mmol/L (Lenski 2015(14)). Our lactate findings therefore extend and reinforce these earlier data. Glucose behaves inversely: septic joints exhibit significantly lower concentrations, an effect exploited by the lactate/glucose ratio in the Berthoud study (1). Rajasekharan et al. further validated this principle using inexpensive urine-strip testing; glucose strip negativity achieved 88 % sensitivity and 76 % specificity, and when combined with a positive leucocyte-esterase strip increased specificity to 88 % ((18). Müller et al. confirmed that synovial glucose is lower in periprosthetic infection, though with only modest diagnostic accuracy (AUC 0.640) (20). Across five major cohorts, synovial lactate consistently demonstrates strong rule-in power for septic arthritis. Thresholds of ≥ 10 mmol/L (11,14) or a lactate: glucose ratio ≥ 5 (Berthoud 2020) deliver specificities of 84–98 % and LR⁺ values up to 27, even when sensitivity is moderate. Carpenter 2020 (3) confirmed that clinical examination alone is inferior, and Müller 2025 (20) extended these findings to PJI, showing that a combined rule (pH ≤ 7.25 or lactate ≥ 8.45 mmol/L or glucose ≤ 18 mg/dL) raises sensitivity to 81 % despite individually modest AUCs. Interleukin-6 (IL-6) Our IL-6 cut-off of 7 000 pg/mL produced an AUC of 0.87, sensitivity 79 %, specificity 85 %, LR+ 5.3, LR− 0.25. Study N Cut-off (pg/mL) AUC Sens % Spec % LR+ Lenski 2014 62 > 7 000 0.803 92.5 64.1 — Lenski 2015 69 ≥ 30 750 0.959 90 94.7 17.3 Sharma 2020 107 > 417* 0.864 74 88 — Park 2025 31 ~105 ng/mL (≈105 000 pg/mL) 0.667 83 72 — *ng/mL converted to pg/mL where possible. These findings reinforce IL-6 as the most sensitive single biomarker for early exclusion of infection. Synovial IL-6 shows outstanding discriminatory ability in periprosthetic infection (Lenski 2014 AUC 0.959) (11) and excellent accuracy in native septic arthritis (AUC ≈ 0.80). Our cutoff of ≈ 7 000 pg/mL aligns with these ranges. Sharma 2020 (17) and Park 2025 (21) confirm its utility even when combined with other markers, highlighting IL-6 as the most sensitive single synovial biomarker for rapid exclusion of infection. Synovial interleukin-6 (IL-6) was our second most accurate marker (AUC 0.87). Lenski and Scherer first highlighted IL-6 as an inflammatory discriminator in native septic arthritis (AUC 0.803) (Lenski 2014 (11)) and later showed even higher accuracy in periprosthetic infections (AUC 0.959, cut-off 30,750 pg/mL) (Lenski 2015). Comparable results have been reported in extensive biomarker panels where IL-6 achieved AUCs of 0.864 (Sharma 2020(17)) and remained significant when combined with serum CRP and synovial WBC (Park 2025(21)). Other cytokines such as IL-1β, IL-17A, and IL-8 also discriminate infection, but our findings and those of Sharma et al. (17) confirm that IL-6 offers the best balance of speed and accuracy for routine practice. Synovial Cell Count and Rapid Bedside Tests Despite the promise of metabolic and cytokine assays, synovial WBC count remains indispensable. The multicenter study of 719 patients reported an AUC of 0.850 with an optimal threshold of 6.7 × 10³/µL (15). Sharma et al. achieved even higher accuracy in periprosthetic infection (AUC 0.952, sensitivity 89 %, specificity 98 %) (17), while Park et al. confirmed strong performance in native joints (AUC 0.837) (21). Our own WBC results (AUC 0.80) are consistent with these ranges. Low-cost point-of-care tests complement laboratory counts. Rajasekharan et al. showed that a positive (++/+++) leucocyte-esterase strip had 92 % sensitivity, and combined LE + glucose negativity increased diagnostic accuracy to 86.7 % (16). These data highlight a feasible strategy for resource-limited settings. Synovial WBC and Classic Indices Study Cut-off (cells/µL) AUC Sens % Spec % LR+ Lenski 2014 > 50 000 0.782 — — 8.49 Infect Dis 2015 > 6.7 × 10³ 0.850 81.8 76.5 3.41 Sharma 2020 > 1.1 × 10³ 0.952 89 98 — Park 2025 > 34 200 0.837 83 76 — Our WBC results (AUC 0.80; LR+ 4.5) lie squarely within these ranges, supporting its continued use alongside metabolic assays. Despite newer markers, the synovial WBC count remains indispensable. Across diverse populations, cut-offs vary (6.7 × 10³ to > 50 × 10³ cells/µL), but AUCs remain strong (0.78–0.95). Our findings (AUC 0.80) sit squarely within these ranges, reinforcing WBC as a robust adjunct that complements lactate and IL-6 for both rule-in and rule-out strategies. Novel metabolites such as synovial d-lactate, produced exclusively by bacteria, offer exciting possibilities. Karbysheva et al. demonstrated sensitivity of 94 % and specificity up to 89 % for periprosthetic joint infection, with the highest levels in Staphylococcus aureus and streptococcal infections (22). Müller et al. extended the metabolic concept by showing that combined assessment of synovial pH, lactate, and glucose improved sensitivity to 81 % (20). Multivariate modelling of routine and novel markers is also promising: Park et al. found that combining serum CRP with synovial WBC yielded an AUC of 0.853 and 100 % negative predictive value, rising to 0.887 when pentraxin-3, IL-6, and presepsin were added (21). Rapid Bedside Tests Rajasekharan et al. (2025) validated low-cost urine-strip surrogates in 75 native effusions: Test Sens % Spec % LR+ Accuracy % Leucocyte esterase (++/+++) 92 70 3.07 77.3 Glucose strip (–/trace) 88 76 3.67 80.0 Combined LE++/+++ + Glucose– 84 88 7.0 86.7 These provide practical options when formal chemistry is unavailable. Point-of-care testing can achieve diagnostic performance comparable to laboratory assays. Rajasekharan 2025 showed that combining leucocyte esterase (++/+++) with glucose strip negativity yields specificity 88 % and LR⁺ 7.0, providing a rapid, inexpensive screen. Novel markers such as d-lactate (Karbysheva 2020, sensitivity > 90 %) and α-defensin (Sharma 2020, AUC 0.916) offer high accuracy but require specialized assays. Emerging Biomarkers Study Biomarker Cut-off AUC Sens % Spec % Karbysheva 2020 d-lactate ≥ 1.3 mmol/L — 94.3 78.4–88.6 Sharma 2020 α-defensin — 0.916 88 95 Synovial CRP > 5.65 mg/L 0.921 80 92 Müller 2025 Combined pH ≤ 7.25 / lactate ≥ 8.45 / glucose ≤ 18 — — 81 62 Park 2025 Multi-marker (CRP+WBC+PTX3+IL-6+Presepsin) — 0.887 100 64 These markers are not yet routine but illustrate future directions. Microbiology Across all nine studies—including ours—Staphylococcus aureus remains dominant: Study Most Common Pathogens Lenski 2014 S. aureus, β-hemolytic streptococci Rajasekharan 2025 S. aureus 21 %, Group B strep 5 %, S. pneumoniae 4 %, E. coli 1 % Sharma 2020 Staph epidermidis, S. aureus, Enterococcus spp., Gram-negatives Karbysheva 2020 Highest d-lactate in S. aureus and streptococci Our cohort S. aureus 38 %, coagulase-negative staphylococci 17 %, streptococci 14 %, Gram-negative bacilli 21 % This uniformity supports empiric therapy covering staphylococci and streptococci while awaiting culture. The bacteriologic profile of our cohort mirrors these international studies. Staphylococci, particularly S. aureus, were dominant—similar to Lenski’s European data (Lenski 2014) and the Indian series of Rajasekharan et al. (16)—followed by β-hemolytic streptococci and occasional Gram-negative bacilli. Such concordance supports empiric coverage targeting staphylococci and streptococci while awaiting definitive cultures. Across all nine studies and our cohort, Staphylococcus aureus remains the dominant pathogen, followed by β-hemolytic streptococci and a minority of Gram-negative bacilli. This uniform global pattern supports empiric coverage targeting staphylococci and streptococci as the cornerstone of initial antimicrobial therapy while awaiting culture confirmation. Clinical Implications • Rule-in: Synovial lactate ≥ 10 mmol/L or lactate/glucose ratio ≥ 5 offers immediate confirmation (specificity ~98 %, LR+ up to 27). • Rule-out: IL-6 < 7 000 pg/mL or WBC < 6.7 × 10³/µL markedly lowers post-test probability. • Low-resource settings: LE + glucose strip combination yields accuracy 86.7 % (12). • Adjuncts: d-lactate (18) and pentraxin-3 (11) may further refine probability estimates when available. Limitations This study has several important limitations. • Single-center design and moderate sample size – Although we enrolled a comparatively large number of culture-proven septic arthritis cases, the findings may not capture the full epidemiologic diversity seen across regions. • Exclusion of culture-negative septic arthritis – To preserve a strict microbiologic gold standard, culture-negative cases were excluded; this likely overestimates specificity of lactate and IL-6 compared with real-world practice, where up to 20 % of septic joints can be culture-negative (1,13). • Limited biomarker panel – We focused on synovial lactate and IL-6 as primary markers. Emerging candidates such as d-lactate (18), α-defensin (Sharma 2020), pentraxin-3 and presepsin (19) were not routinely available and therefore not tested, preventing direct head-to-head comparison. • Potential spectrum bias – Patients were recruited from a tertiary referral center; the relatively high prevalence of severe infection and staphylococcal predominance could inflate positive likelihood ratios compared with community cohorts (11,20). • Timing of sampling and prior therapy – Although recent antibiotic exposure was an exclusion criterion, subtle variations in symptom duration or undocumented pre-hospital treatment might have influenced cytokine or metabolite concentrations. • Single time-point analysis – We did not perform serial measurements. Dynamic changes in IL-6 or lactate, shown to have prognostic value in other infections, could not be assessed. Despite these limitations, the prospective design, strict microbiologic confirmation, and inclusion of multiple comparator biomarkers strengthen the internal validity and allow meaningful comparison with published cohorts. Nevertheless, the convergence of findings across Europe, Asia, and North America provides strong external validity.

In this prospective evaluation of acute native joint effusions, synovial lactate and interleukin-6 (IL-6) emerged as the most powerful rapid biomarkers for septic arthritis. • A synovial lactate ≥ 10 mmol/L demonstrated the highest diagnostic accuracy (AUC ≈ 0.90) with sensitivity ≈ 76 %, specificity ≈ 88 %, and a positive likelihood ratio of >6, confirming and extending the performance reported by Berthoud 2020 (AUC 0.859) and Lenski 2014 (AUC 0.864). • Synovial IL-6 ≥ 7 000 pg/mL achieved an AUC of ≈ 0.87, sensitivity ≈ 79 %, and specificity ≈ 85 %, consistent with prior native and periprosthetic studies showing AUCs of 0.80–0.96 (13,15). • Synovial WBC counts, while valuable (AUC ≈ 0.80), offered lower discriminatory power than lactate or IL-6, echoing large multicenter findings (14,16). Across our cohort, the microbial spectrum mirrored global epidemiology, dominated by Staphylococcus aureus (≈ 38 %), coagulase-negative staphylococci (≈ 17 %), and β-hemolytic streptococci (≈ 14 %), with Gram-negative bacilli accounting for ≈ 21 %, paralleling observations in Europe and Asia (11,16,18). Clinical implications: Rapid measurement of synovial lactate and IL-6 provides clinicians with actionable data within hours—well before culture results—to confidently rule in infection when elevated and substantially lower post-test probability when normal. Incorporating these assays into routine synovial fluid analysis can shorten time to diagnosis, guide early antimicrobial therapy, and reduce joint destruction. Future multicenter studies should validate these thresholds across diverse settings and evaluate integration with novel markers such as d-lactate, α-defensin, pentraxin-3, and presepsin to further refine diagnostic algorithms for both native and periprosthetic joint infections.

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