Francisella tularensis Bone and Joint Infections: United States, 2004-2023.

Tularemia is caused by the highly infectious bacterium Francisella tularensis, which is recognized as a Tier 1 bioterrorism agent. Tularemia has a range of recognized clinical manifestations, but fewer than 20 bone or joint infections from 6 countries have been reported in the literature to date. This series includes 13 cases of F. tularensis septic arthritis or osteomyelitis in the United States during 2004-2023 and describes exposures, clinical presentation, diagnosis, and outcomes for this rare but severe form of tularemia. Clinicians should consider F. tularensis in patients with compatible exposures or a history of joint replacement or immunosuppression.

Rapid high-throughput processing of tissue samples for microbiological diagnosis of periprosthetic joint infections using bead-beating homogenization.

Enrichment of periprosthetic tissue samples in blood culture bottles (BCBs) for microbiological diagnosis of periprosthetic joint infections (PJI) is more reliable than the use of an enrichment broth. Nevertheless, the extremely time-consuming homogenization of the samples for BCB processing has so far limited its use, especially in high-throughput settings. We aimed to establish a highly scalable homogenization process of tissue samples for long-term incubation in BCBs. A protocol for homogenization of tissue samples using bead beating was established and validated. In a second step, the use of the homogenate for enrichment in BCBs was compared to the use of thioglycolate broth (TB) in terms of diagnostic accuracy using clinical tissue samples from 150 patients with suspected PJI. Among 150 analyzed samples, 35 samples met the microbiological criteria for PJI. Using BCB, 32 of 35 (91.4%) PJI were detected compared to 30 of 35 (85.7%) by TB. The use of BCB had a lower secondary contamination rate (2/115; 1.7% vs 4/115; 3.5%) but the trend was not significant due to low numbers of samples (P = 0.39). The time to process a batch of 12 samples using the established homogenization method was 23 ± 5 min (n = 10 batches). We established and validated a homogenization workflow that achieves the highest sensitivity in the microbiological diagnostic of PJI. The enrichment of the tissue homogenate in BCBs showed equally good results as the use of enrichment broth and allows semi-automated high-throughput processing while demonstrating lower contamination rates in our study.

Evaluation of Surveillance System Changes to Improve Detection of Disseminated Gonococcal Infections in Virginia, 2018 to 2021.

BACKGROUND: Disseminated gonococcal infection (DGI), a complication of untreated gonorrhea, is rarely reported through routine surveillance. We sought to improve local surveillance system capacity to estimate and monitor the incidence of DGI in Virginia. METHODS: We modified surveillance protocols to identify possible DGI cases using information extracted from gonorrhea case reports and performed provider follow-up using standardized case report forms to confirm DGI diagnosis and collect clinical information. Suspect cases included those with a laboratory report indicating sterile site of specimen collection (e.g., blood, synovial fluid) and/or intravenous (IV) treatment. We performed descriptive analyses to summarize the characteristics of suspect and confirmed DGIs and estimated incidence. RESULTS: After piloting protocols in 2018 to 2019, we identified 405 suspect DGI cases from 29,294 gonorrhea cases reported in 2020 to 2021 (1.4%). We initiated investigations for 298 (73.6%) of the suspect cases, received provider responses for 105 (25.9%), and confirmed 19 DGI cases (4.7%). Positive laboratory reports from nonmucosal sites were the most reliable predictor of confirmed DGI status, but most were not confirmed as DGI even when provider follow-up was successful. The confirmed and estimated incidence of DGI were 0.06% and 0.22%, respectively. Sixteen (84%) of the confirmed cases were older than 25 years, 3 (16%) were HIV positive, and approximately half were male and non-Hispanic Black. Most (15 [74%]) were hospitalized, and common manifestations included septic arthritis and bacteremia. CONCLUSIONS: We improved surveillance for DGI in Virginia while incurring minor programmatic costs. Additional efforts to improve the completeness and quality of surveillance data for DGI are needed.

Infective endocarditis and septic arthritis caused by Corynebacteriumstriatum.

Corynebacterium striatum occasionally causes nosocomial infections, such as catheter-related bloodstream infection and pneumonia; however, C. striatum-related infective endocarditis or septic arthritis is uncommon. We present the case of an 85-year-old woman with infective endocarditis at the native valve and septic arthritis at the native shoulder joint caused by C. striatum. The patient was admitted for a 10-day history of fever and right shoulder pain. She had no history of artificial device implantation, injury, arthrocentesis, or hospitalization. A physical examination revealed conjunctival petechiae, a systolic heart murmur, and right shoulder joint swelling. C. striatum was observed in two blood culture sets. Transesophageal echocardiography revealed vegetation in the right aortic coronary cusp. Arthrocentesis at the right shoulder aspirated pyogenic fluid and C. striatum was detected in the culture. The patient was diagnosed with infective endocarditis and septic arthritis caused by C. striatum, and ampicillin was administered based on antimicrobial susceptibility test results. The patient's condition was initially stable; however, she developed pulmonary congestion on day 56 and eventually died. An autopsy demonstrated perforation of the aortic left coronary cusp with vegetation. C. striatum may cause native valve endocarditis and native joint septic arthritis.

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. QUESTIONS/PURPOSES: (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? METHODS: Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. RESULTS: Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. CONCLUSION: Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. LEVEL OF EVIDENCE: Level II, diagnostic study.

Arthroscopic Treatment Is a Safe and Effective Alternative to Open Treatment for Acute Septic Arthritis of the Native Knee: A Systematic Review.

PURPOSE: To compare complication rates, reoperation rates, and subjective outcomes after arthroscopic and open irrigation and debridement for treatment of native knee septic arthritis. METHODS: Following The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review of the Embase, Cochrane, and PubMed databases was performed. Comparative studies reporting clinical outcomes after arthroscopic versus open treatment for septic arthritis of the native knee in human adults were included. Excluded were case series with <10 patients, inclusion of patients <18 years old, studies on non-native joints, abstract-only publications, and studies without stratification of the involved joint. Two reviewers in duplicate independently performed search and data extraction. The quality of the included studies was assessed with the Methodological Index for Non-Randomized Studies instrument. The mean score among the included studies was 18.2 (range 16-23). RESULTS: Eleven studies were included, comprising 2,343 knees treated arthroscopically, and 1,595 treated with arthrotomy. Studies reported no differences in erythrocyte sedimentation rate, C-reactive protein, peripheral white blood cells, or symptom chronicity between groups. Nine studies (81.8%) attempted to control for potentially confounding variables in their analyses, and 4 studies (36.4%) reported significant differences in patient characteristics. Reoperation rates ranged from 0% to 50% for arthroscopy and 6% to 71% for arthrotomy. Complication rates ranged from 0% to 39.4% arthroscopically and 0% to 49% for arthrotomy. Superior patient-reported outcomes were achieved after arthroscopy in 2 studies that analyzed subjective outcomes. CONCLUSIONS: Arthroscopic management of native knee septic arthritis is a safe and effective alternative to open treatment and is associated with comparable complication rates, reoperation rates, hospitalization lengths, readmission rates, and superior patient-reported outcomes compared with open irrigation and debridement. LEVEL OF EVIDENCE: Level IV, systematic review of Level I, III, and IV studies.

Consensus on the definition and criteria for failure of surgical treatment in bacterial arthritis of a native joint: An international Delphi study.

PURPOSE: The literature presents a wide range of success rates for a single surgical intervention of bacterial-septic-arthritis, and there is a lack of clear criteria for identifying treatment failure and making decisions about reintervention. This Delphi study aims to establish a consensus among an international panel of experts regarding the definition of treatment failure and the criteria for reintervention in case of bacterial arthritis. METHODS: The conducting and reporting Delphi studies (CREDES) criteria were used. Data from a systematic review was provided as the basis for the study. A list of 100 potential experts were identified. The study was designed and conducted as follows: (I) identification and invitation of an expert panel, (II) informing the participating expert panel on the research question and subject, and (III) conducting two or three Delphi rounds to reach consensus on explicit research items. Potential criteria were rated on a five-point Likert scale. RESULTS: Sixty orthopaedic experts from nine countries participated in this Delphi study, with 55 completing all three rounds. The mean experience as an orthopaedic surgeon was 15 years (SD ± 9). Strong (96%) consensus was reached on the definition of treatment failure: the persistence of physical signs of arthritis (e.g., pain and swelling) and/or systemic inflammation (e.g., fever and no improvement in CRP) despite surgical and antibiotic treatment. Furthermore, consensus (>80%) was reached on six criteria influencing the decision for reintervention; pain (81%), sepsis (98%), fever (88%), serum CRP (93%), blood culture (82%), and synovial fluid culture (84%). CONCLUSION: The definition of treatment failure for bacterial arthritis after a single surgical intervention was established through a three-round Delphi study. Additionally, consensus was reached on six criteria that are helpful for determining the need for reintervention. This definition and these criteria may help in the development of clinical guidelines, and will empower physicians to make more precise and consistent decisions regarding reintervention for patients, ultimately aiming to reduce over- and undertreatment and improve patient outcomes. LEVEL OF EVIDENCE: Level V.

Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. METHODS: We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. RESULTS: Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, P < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, P < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, P < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, P < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, P < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. CONCLUSION: In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI.

Can the Current Thresholds for Synovial Cell Count and Neutrophil Percentage to Diagnose Prosthetic Joint Infection be Applied to Metal-on-Metal Rotating Hinge Total Knee Arthroplasty?

BACKGROUND: Synovial leukocyte count analysis is an important tool in the diagnosis of PJI. However, results can be poor if metallosis is present. The issue of metallosis was established for some rotating hinge knee arthroplasty designs. METHODS: This was a retrospective single-center analysis that included 108 patients who had a single-design metal-on-metal rotating hinge knee arthroplasty who underwent revision surgery and had prior synovial fluid analysis performed. The diagnostic accuracy of leukocyte count and the percentage of polymorphonuclear neutrophiles (% PMN) were investigated. RESULTS: Patients who had a PJI had a higher median leukocyte count and % PMN compared to aseptic revisions (7,905/µL (interquartile range (IQR) 2,419 to 37,400) and 85% (IQR 70.3 to 93.8) versus 450 (IQR 167 to 1,215) and 46% (IQR 28.5 to 67.4%), P < .001). The respective areas under the curves were 0.916 (95% confidence interval 0.862 to 0.970) for leukocyte count and 0.821 (95% confidence interval 0.739 to 0.902) for % PMN. We calculated an optimal cut-off value of 1,200 leukocytes/µL (Sensitivity 94.5%/specificity 75.5%) and 63% PMN (Sensitivity 85.5%/specificity 73.6%) to define PJI. Established thresholds were less sensitive, but more specific. The "infection likely" scenario of the European Bone and Joint Infection Society (EBJIS) definition was closest to the calculated thresholds. CONCLUSION: Currently used thresholds for leukocyte cell count and %PMN to define PJI were less sensitive and specific in the diagnosis of PJI in metal-on-metal RHK knees. Surgeons must consider lower cut-off values when evaluating such implants for PJI.

Utility of Synovial Fluid Biomarkers for Culture-Positive Septic Arthritis in a Lyme Disease-Endemic Region.

OBJECTIVE: To evaluate the performance of synovial fluid biomarkers to identify children with culture-positive septic arthritis. METHODS: We identified children 6 months to 18 years old presenting to a single emergency department between 2007 and 2022 undergoing evaluation for septic arthritis defined by having a synovial fluid culture obtained. Our primary outcome was septic arthritis defined by a positive synovial fluid culture. We evaluated the ability of synovial fluid biomarkers to identify children with septic arthritis using area under the receiver operating characteristic curve (AUC) analyses. We measured the sensitivity and specificity of commonly used synovial fluid biomarkers. RESULTS: We included 796 children, of whom 79 (10%) had septic arthritis. Compared with synovial white blood cell count (AUC, 0.72; 95% confidence interval [CI], 0.65-0.78), absolute neutrophil count (AUC, 0.72; 95% CI, 0.66-0.79; P = 0.09), percent neutrophils (AUC, 0.66; 95% CI, 0.60-0.71; P = 0.12), and glucose (AUC, 0.78; 95% CI, 0.67-0.90; P = 0.33) performed similarly, whereas protein (AUC, 0.52; 95% CI, 0.40-0.63, P = 0.04) had lower diagnostic accuracy. Synovial fluid white blood cell count ≥50,000 cells/µL had a sensitivity of 62.0% (95% CI, 50.4%-72.7%) and a specificity of 67.0% (95% CI, 63.4%-70.4%), whereas a positive synovial fluid Gram stain had a sensitivity of 48.1% (95% CI, 36.5%-59.7%) and specificity of 99.1% (95% CI, 98.1%-99.7%) for septic arthritis. CONCLUSIONS: None of the routinely available synovial fluid biomarkers had sufficient accuracy to be used in isolation in the identification of children with septic arthritis. New approaches including multivariate clinical prediction rules and novel biomarkers are needed.

Efficacy and Accuracy of Diagnosing Septic Arthritis: How Effective are Current Methods for Timely Diagnosis of Septic Arthritis?

The diagnosis of septic arthritis requires a reliance on ancillary tests, including synovial fluid white blood cell count (jWBC), percentage of polymorphonuclear leukocytes (%PMN), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). This study evaluated these tests to determine their diagnostic utility in suspected septic arthritis. A retrospective chart review was performed on patients admitted to an urban hospital who underwent arthrocentesis. The authors evaluated the jWBC, %PMN, ESR, and CRP with receiver operating characteristic (ROC) curve analyses. Two hundred sixty-five patients met inclusion criteria. Sixty-three had a culture-positive aspirate. ROC curve analysis resulted in an area under the curve (AUC) of 0.80 for jWBC with cutoff point of 22,563 cells/mm3 and an AUC of 0.71 for %PMN with cutoff point of 90.5%. CRP and ESR had AUC values of 0.62 and 0.61, respectively. The culture-positive cohort had higher elevations in all assessed diagnostic tests. However, AUC data for ESR and CRP showed little diagnostic utility. Additionally, sensitivities and specificities of jWBC and %PMN were too low. Associated cutoff points would result in excessive unnecessary operative intervention. Further studies should incorporate synovial fluid biomarkers into the workup of a suspected septic joint. (Journal of Surgical Orthopaedic Advances 33(2):108-111, 2024).

Executive Summary: Periprosthetic Joint Infection-Current Clinical Challenges.

Over the last several decades, periprosthetic joint infection (PJI) has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of PJI, focusing on frequent clinical challenges and collaborative interdisciplinary care. The more detailed review including diagnosis, surgical considerations, and a detailed antimicrobial discussion is presented in the online version.

Periprosthetic Joint Infection: Current Clinical Challenges.

Over the last several decades, periprosthetic joint infection has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of periprosthetic joint infection, focusing on frequent clinical challenges and collaborative interdisciplinary care.

Next-Generation Sequencing Supports Targeted Antibiotic Treatment for Culture Negative Orthopedic Infections.

The isolation of an infective pathogen can be challenging in some patients with active, clinically apparent infectious diseases. Despite efforts in the microbiology lab to improve the sensitivity of culture in orthopedic implant-associated infections, the clinically relevant information often falls short of expectations. The management of peri-prosthetic joint infections (PJI) provides an excellent example of the use and benefits of newer diagnostic technologies to supplement the often-inadequate yield of traditional culture methods as a substantial percentage of orthopedic infections are culture-negative. Next-generation sequencing (NGS) has the potential to improve upon this yield. Bringing molecular diagnostics into practice can provide critical information about the nature of the infective organisms and allow targeted therapy in these otherwise challenging situations. This review article describes the current state of knowledge related to the use and potential of NGS to diagnose infections, particularly in the setting of PJIs.

Targeted Versus Shotgun Metagenomic Sequencing-based Detection of Microorganisms in Sonicate Fluid for Periprosthetic Joint Infection Diagnosis.

BACKGROUND: Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly. Here, 16S ribosomal RNA (rRNA) gene-based targeted metagenomic sequencing (tNGS) was compared to sNGS of sonicate fluid for microbial detection and identification in patients with total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure. METHODS: A convenience sample of sonicate fluids derived from patients who had undergone THA or TKA removal, enriched with culture negative PJI cases, was tested. Samples had been previously tested by sNGS. For tNGS, samples were extracted, amplified by polymerase chain reaction targeting the V1 to V3 regions of the 16S rRNA gene, and sequenced on an Illumina MiSeq. RESULTS: A total of 395 sonicate fluids, including 208 from subjects with PJI, were studied. Compared with sonicate fluid culture, tNGS had higher positive percent agreement (72.1 vs 52.9%, P < .001), detecting potential pathogens in 48.0% of culture-negative PJIs. There was no difference between the positive percent agreement of tNGS (72.1%) and sNGS (73.1%, P = .83). CONCLUSIONS: 16S rRNA gene-based tNGS is a potential diagnostic tool for PJI pathogen identification in sonicate fluid from failed THAs and TKAs in culture-negative cases, with similar performance characteristics to sNGS.

Automatic Detection of Two Synovial Fluid Periprosthetic Joint Infection Biomarkers on an Integrated Microfluidic System.

Post-arthroplasty periprosthetic joint infection (PJI) is a serious ailment that can be difficult to diagnose. Herein, we developed a novel integrated microfluidic system (IMS) capable of detecting two common PJI biomarkers, alpha defensin human neutrophil peptide 1 (HNP-1) and C-reactive protein (CRP), from synovial fluid (SF). A magnetic bead-based one-aptamer-one-antibody assay was carried out automatically within 45 min on a single chip for simultaneous detection of both biomarkers at concentration ranges of 0.01-50 (HNP-1) and 1-100 (CRP) mg/L. It is the first report for utilizing these two biomarkers as targets to establish the new one-aptamer-one-antibody assay to detect PJI on-chip, and the aptamers demonstrated high specificity to their SF targets. As 20 clinical samples were correctly diagnosed with our IMS (verified by a common gold standard kit), it could serve as a promising tool for PJI diagnostics.

Performance and Hypothetical Impact on Joint Infection Management of the BioFire Joint Infection Panel: a Retrospective Analysis.

Pathogen identification is key in septic arthritis. Culture-based techniques are challenging, especially when patients have been pretreated with antibiotics or when difficult-to-culture bacteria are encountered. The BioFire joint infection assay (BJA) is a multiplex PCR panel which detects 31 of the most prevalent bacterial and fungal pathogens causing septic arthritis. Here, 123 cryoconserved contemporary synovial fluid samples from 120 patients underwent BJA analysis. Results were compared to those of culture-based diagnostics (standard of care [SOC]). Clinical data were collected, and the possible impact of the molecular diagnostic application on patient management was evaluated. Fifteen of 123 synovial fluid cultures grew bacterial pathogens. All on-panel pathogens (9/15) were correctly identified by the BJA. The BJA identified four additional bacterial pathogens in four SOC-negative cases. BJA sensitivity and specificity were 100% (95% confidence interval [CI], 69.2% to 100%) and 100% (95% CI, 96.8% to 100%), respectively. Compared to the SOC, the BJA would have resulted in faster provision of species identification and molecular susceptibility data by 49 h and 99 h, respectively. Clinical data analysis indicates that in BJA-positive cases, faster species ID could have led to timelier optimization of antibiotic therapy. This retrospective study demonstrates high sensitivity and specificity of the BJA to detect on-panel organisms in bacterial arthritis. The usefulness of the BJA in prosthetic-joint infections is limited, as important pathogens (i.e., coagulase negative staphylococci and Cutibacterium acnes) are not covered. Evidence from patient data analysis suggests that the assay might prove valuable for optimizing patient management in acute arthritis related to fastidious organisms or for patients who received antibiotics prior to specimen collection.

Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.

Rapid Diagnostics of Joint Infections Using IS-Pro.

Diagnosis of bone and joint infections (BJI) relies on microbiological culture which has a long turnaround time and is challenging for certain bacterial species. Rapid molecular methods may alleviate these obstacles. Here, we investigate the diagnostic performance of IS-pro, a broad-scope molecular technique that can detect and identify most bacteria to the species level. IS-pro additionally informs on the amount of human DNA present in a sample, as a measure of leukocyte levels. This test can be performed in 4 h with standard laboratory equipment. Residual material of 591 synovial fluid samples derived from native and prosthetic joints from patients suspected of joint infections that were sent for routine diagnostics was collected and subjected to the IS-pro test. Bacterial species identification as well as bacterial load and human DNA load outcomes of IS-pro were compared to those of culture. At sample level, percent positive agreement (PPA) between IS-pro and culture was 90.6% (95% CI 85.7- to 94%) and negative percent agreement (NPA) was 87.7% (95% CI 84.1 to 90.6%). At species level PPA was 80% (95% CI 74.3 to 84.7%). IS-pro yielded 83 extra bacterial detections over culture for which we found supporting evidence for true positivity in 40% of the extra detections. Missed detections by IS-pro were mostly related to common skin species in low abundance. Bacterial and human DNA signals measured by IS-pro were comparable to bacterial loads and leukocyte counts reported by routine diagnostics. We conclude that IS-pro showed an excellent performance for fast diagnostics of bacterial BJI.

Multicenter evaluation of BioFire JI panel related to improved microbiological diagnostics on acute osteoarticular infections.

Microbiological diagnosis of osteoarticular infections (OI) is crucial for a successful treatment. A prospective multicenter study including 262 synovial fluids with suspicion of acute OI was performed between July 2021 and October of 2022. BioFire Joint Infection Panel multiplex-PCR test was performed and results were compared with conventional cultures of synovial fluid specimens. In total, 136 microorganisms were detected, and fourteen samples were positive for more than one microorganism. In monomicrobial infections (n = 87) agreement with culture was 69%. In 26 samples, the multiplex PCR yield an additional positive result when culture result was negative. It helped in the detection of fastidious microorganisms as K. kingae and N. gonorrhoeae. This multiplex PCR has proven to be a useful technique that can be used for patients with high suspicion of acute OI in a rapid and automated manner.