Culture-negative Periprosthetic Joint Infection Research Articles

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study

BackgroundThis study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI).MethodsA retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed.ResultsmNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37).ConclusionsMetagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

Culture-negative periprosthetic joint infections: Do we have an issue?

Culture-negative periprosthetic joint infection (PJI) poses a significant challenge in clinical settings. The lack of information on causative organism(s) leads to uncertainties regarding the choice of antimicrobial treatment, which can potentially adversely influence the outcome. Recent advances in molecular-based diagnostic methods have the potential to address the difficulties associated with culture-negative PJIs. These technologies offer a solution to the existing clinical dilemma by providing identification of pathogens and guiding appropriate antimicrobial treatment.In this narrative review, we provide information regarding: 1) incidence and risk factors for culture-negative PJI; 2) the optimal antimicrobial therapy and duration of treatment for culture-negative PJI; 3) outcome comparison between culture-positive and culture-negative PJI; and 4) utilization of novel molecular diagnostic methods in culture-negative PJI, including pathogen identification, and the implementation of an antibiotic stewardship program.

Mild aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL)-type reactions also present in patients with failed knee prostheses.

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses.

Commercial Synovial Antigen Testing is Inferior to Traditional Culture for the Diagnosis of Periprosthetic Joint Infection in Patients Undergoing Revision Total Knee Arthroplasty

BackgroundDespite its limitations, a culture remains the “gold standard” for pathogen identification in patients who have periprosthetic joint infection (PJI). Recently, a synovial fluid antigen test has been introduced by a commercial entity. The purpose of this multicenter study was to determine the accuracy of the antigen test in the diagnosis of PJI. MethodsThis retrospective study identified 613 patients undergoing revision total knee arthroplasty who had undergone preoperative synovial fluid analysis. A PJI was defined using the 2018 International Consensus Meeting (ICM) criteria. Patients who had an extended period (> 180 days) from aspiration to revision procedure (n = 62), those presenting within 90 days of their index arthroplasty procedure (n = 17), and patients who had an inconclusive ICM score (n = 8) were excluded. Using receiver operator characteristic curve analyses, we examined the utility of the microbial identification (MID) antigen test and any positive culture (either preoperative or intraoperative) in the diagnosis of PJI. ResultsA total of 526 patients were included. Of these, 125 (23.8%) were ICM positive and 401 (76.2%) were ICM negative. Culture demonstrated an area under the curve (AUC) of 0.864, sensitivity of 75.2%, and specificity of 97.5%. On the other hand, the MID test exhibited an AUC of 0.802, sensitivity of 61.6%, and specificity of 98.8%. The AUC of culture was significantly higher than that of the MID test (P = .037). The MID test was positive in 41.9% of culture-negative PJI cases. We also observed a high rate of discordance (29.7%) when both culture and the MID test were positive in the ICM-positive group. ConclusionsSynovial fluid antigen testing does not provide additional clinical benefit when compared to traditional cultures for the diagnosis of PJI. The antigen test had low sensitivity in the diagnosis of PJI and a relatively high rate of discordance with culture. Level of EvidenceLevel III.

What Is the Rate of Antimicrobial Resistance of a Prosthetic Joint Infection in a Major Orthopaedic Centre?

Periprosthetic joint infections (PJIs) are important factors in decreasing the success of hip and knee arthroplasties. It is a necessity to explore the epidemiological data and develop applications for rational antibiotic use, to address future infection control concerns. We aimed to investigate the microorganisms that were responsible and the related antibiograms in 121 patients with PJI, who were managed by two-stage revision surgery. Patients' data records, demographics, comorbidities, sites of arthroplasty, synovial fluid and deep tissue culture results and antibiotic treatment were summarized on a standardized case report form. There were 43 (35.5%) culture-negative PJI cases and 12 (9.9%) polymicrobial growths. The causative pathogens included Gram-positive (50.4%) and Gram-negative microorganisms (23.1%) and fungi (0.8%). Methicillin resistance was 64.3% for S. aureus and 89.5% for coagulase-negative staphylococcus (CoNS). The extended spectrum beta lactamase (ESBL) rate for Enterobacteriaceae was 68.4%. This study shows that antibiotic resistance is encountered in more than half of the cases, which is valid for all microorganisms most common in PJI. The success of treatment decreases significantly in cases where antibiotic-resistant microorganisms are isolated or in cases where the culture is negative.

Periprosthetic joint infections in patients with rheumatoid arthritis are associated with higher complication and mortality rates.

Periprosthetic joint infection (PJI) remains the most devasting complication after total joint arthroplasty (TJA). There has been a significant focus on this topic in recently-published medical literature. However, relatively little has been published about PJI in patients with rheumatoid arthritis (RA), which are often physiologically frail and immunocompromised. A better understanding of PJI in this patient population is therefore crucial. The main aims of this paper are to (1) report complication and mortality rates in a cohort of PJI-RA patients; and (2) clinically characterize them. Medical and surgical records of all RA PJI patients treated surgically from 2003 to 2020 were retrospectively reviewed. Medical history, physical examination, reactive protein (CRP) level, procalcitonin, white blood cell (WBC) count, joint aspiration results, and cultures were used to determine PJI. 54PJIs, 49 of them chronic, were treated in 53RA patients. Mean patient age was 65yrs. (range = 32-88); 33females and 20 males (one bilateral hip). The overall mortality rate was 18.9%(n = 10), with five deaths directly attributed to PJI. Staphylococci accounted for 34 infections (63%), while 11(20.4%) had multiorganism infections and six culture-negative PJI. At the end of treatment 79.6%(n = 43) still had an implanted TJR, 7.4% (n = 4) had spacers, 5.6%(n = 3) had undergone resection arthroplasty, 3.7%(n = 2) arthrodesis, and one each amputation and exarticulation. Mortality and specially complication rates were (are) high in this RA patients group presenting PJI. Delays to diagnosis and treatment may explain some of these poor outcomes. A cohort level III retrospective study.

Efficacy and safety of two-stage revision for patients with culture-negative versus culture-positive periprosthetic joint infection: a single-center retrospective study

BackgroundThe safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years.MethodsData were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis.ResultsThe final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616).ConclusionThe two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Outcomes of culture-negative or -positive periprosthetic joint infections: A systematic review and meta-analysis.

This study overviewed the current database of studies on periprosthetic joint infections (PJIs) to compare outcomes and antibiotic side effects in culture-negative or culture-positive PJIs and assess treatment options for culture-negative PJIs. A systematic review and meta-analysis was undertaken using studies published before July 2022 in MEDLINE, EMBASE, and Cochrane Library. All studies comparing treatment of culture-negative or -positive PJIs were included. Afterward, the infection control rate, periprosthetic or spacer fracture, hip joint or spacer dislocation, and antibiotic side effects in different treatment methods of PJI were analyzed. Eleven studies involving 1,747 patients were included. Most studies clearly defined the infection control criteria: no pain or swelling, no wound drainage, normal serology, and normal radiographic findings. Patients were followed until treatment failure, death, or until the last clinical visit without evidence of treatment failure. The two types of PJIs did not differ significantly in infection control rates (culture-negative PJI 79.2% vs. culture-positive PJI 76.6%; odds ratio [OR]=1.20, 95% confidence interval [CI]: 0.84 to 1.70), either after all types of surgical treatment or after two-stage revision arthroplasty (OR=1.12, 95% CI: 0.72 to 1.75), single-stage revision arthroplasty (OR=0.51, 95% CI: 0.19 to 1.37), or debridement, antibiotics, and implant retention (OR=0.88, 95% CI: 0.50 to 1.54). Similarly, we did not find differences in periprosthetic or spacer fracture and hip joint or spacer dislocation. For culture-negative PJIs, the infection control rate was 85.2% after two-stage revision arthroplasty, 90.6% after single-stage revision arthroplasty, and 69.7% after debridement, antibiotics, and implant retention. Data pooled from three studies showed higher incidence of antibiotic side effects for culture-negative PJIs. The clinical outcomes of one-stage revision and two-stage revision are comparable. Therefore, both of them can be considered in surgical treatment for culture-negative PJIs. In addition, limited data showed a higher incidence of antibiotic side effects in culture-negative PJIs.

What's New in Musculoskeletal Infection.

What's New in Musculoskeletal Infection.

Direct detection and identification of periprosthetic joint infection pathogens by metagenomic next-generation sequencing

This study assessed the application of metagenomic next-generation sequencing in pathogen detection of periprosthetic joint infections. A total of 95 cases who previously had undergone hip and knee replacement undergoing revision from January 2018 to January 2021 were included in this study. Specimens of synovial fluid and deep-tissue were collected for culture and metagenomic next-generation sequencing, and patients were retrospectively categorized as infected or aseptic using the Musculoskeletal Infection Society criteria after revision surgery. The sensitivity, specificity, positive and negative predictive values were compared. A total of 36 cases had positive culture results and 59 cases had positive metagenomic next-generation sequencing results. Culture was positive in 34 infected cases (58.6%) and 2 aseptic cases (5.4%). Metagenomic next-generation sequencing was positive in 55 infected cases (94.8%) and 4 aseptic cases (10.8%). Five cases diagnosed with infection had other potential pathogens detected by metagenomic next-generation sequencing. Among the 24 culture-negative periprosthetic joint infections, metagenomic next-generation sequencing was able to identify potential pathogens in 21 cases (87.5%). From sampling to reporting, the average time needed for culture was 5.2 (95% CI 3.1–7.3) days, while that for metagenomic next-generation sequencing was 1.3 (95% CI 0.9–1.7) days. Metagenomic next-generation sequencing is more advantageous in pathogen detection of periprosthetic joint infection after total joint replacement, especially in patients with multiple infections or negative culture results.

Cultures in periprosthetic joint infections, the imperfect gold standard?

Culture-negative periprosthetic joint infections (PJI) are commonly described in the literature. By implementing a routine diagnostic workup and by optimizing tissue sampling and processing, the culture-negative rate can easily be reduced. When faced with a culture-negative PJI, several serological and molecular techniques are available that may aid in finding the causative microorganism. Clinical clues may guide the treating physician towards more atypical and rare microorganisms. A multidisciplinary team consisting of orthopaedic surgeons, microbiologists and infectious disease specialist are warranted in tailoring diagnostic testing and deciding on the surgical and antibiotic treatment approach.

Utility of Diagnostic Markers in Late Periprosthetic Joint Infection Workup for Total Knee Arthroplasty Patients Who Received Antibiotics 48 Hours Before Aspiration

BackgroundDiagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI. MethodsPatients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group. ResultsThe immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82). ConclusionAntibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients. Level of EvidenceLevel III, retrospective comparative study.

Synovial fluid neutrophil extracellular traps could improve the diagnosis of periprosthetic joint infection.

This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly.Cite this article: Bone Joint Res2023;12(2):113-120.

Nationwide Results of Microorganism Antigen Testing as a Component of Preoperative Synovial Fluid Analysis.

Antigen immunoassays to detect synovial fluid (SF) microorganisms have recently been made available for clinical use. The purpose of this study was to determine the sensitivity and specificity of an SF microorganism antigen immunoassay detection (MID) panel, evaluate the panel's capability to detect microorganisms in the setting of culture-negative periprosthetic joint infection (PJI), and determine diagnostic predictive values of the MID panel for PJI. This study included 67,441 SF samples obtained from a hip or knee arthroplasty, from 2,365 institutions across the United States, submitted to 1 laboratory for diagnostic testing. All data were prospectively compiled and then were analyzed retrospectively. Preoperative SF data were used to classify each specimen by the International Consensus Meeting (2018 ICM) definition of PJI: 49,991 were not infected, 5,071 were inconclusive, and 12,379 were infected. The MID panel, including immunoassay tests to detect Staphylococcus, Candida, and Enterococcus, was evaluated to determine its diagnostic performance. The MID panel demonstrated a sensitivity of 94.2% for infected samples that yielded positive cultures for target microorganisms (Staphylococcus, Candida, or Enterococcus). Among infected samples yielding positive cultures for their respective microorganism, individual immunoassay test sensitivity was 93.0% for Staphylococcus, 92.3% for Candida, and 97.2% for Enterococcus. The specificity of the MID panel for samples that were not infected was 98.4%, yielding a false-positive rate of 1.6%. The MID panel detected microorganisms among 49.3% of SF culture-negative infected samples. For PJI as a diagnosis, the positive predictive value of the MID panel was 91.7% and the negative predictive value was 93.8%. Among MID-positive PJIs, 16.2% yielded a discordant cultured organism instead of that detected by the antigen test. SF microorganism antigen testing provides a timely adjunct method to detect microorganisms in the preoperative SF aspirate, yielding a low false-positive rate and enabling the detection of a microorganism in nearly one-half of SF culture-negative PJIs. Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Successful eradication rate following one-stage septic knee and hip exchange in selected pre-operative culture-negative periprosthetic joint infections.

The main requirement for performing the one-stage septic exchange is the pre-operative identification of the pathogen and its susceptibility. The purpose of this study is to evaluate the success rate with special focus on reinfection in a cohort of patients who underwent one-stage septic knee or hip revision for pre-operative culture-negative PJI. We retrospectively analyzed 640 patients treated by one-stage revision for chronic knee or hip PJI between January 1, 2016, and December 31, 2018. Only cases with pre-operative culture-negative PJI, with culture-negative synovial aspirations and one negative open biopsy, were analyzed. We evaluated the septic and aseptic complication and the rate of complication-free survival defined as the time from the date of first operation and the date of complication events. A total of 22 patients fulfilled the inclusion and were enrolled. The mean age of the group was 73.2 ± 9.8years, with a median ASA score of 3 (range 3-4). After mean follow-up of 3.6 ± 2.6years, 86.4% (19 out of 22) of patients reported no complications. Two patients (9.1%) after one-stage hip required revision arthroplasty due to septic failure, while one patient (4.5%) with one-stage knee had revision for femoral component aseptic loosening. Our analysis suggests that the absence of pre-operative pathogen detection may not be contraindication to the one-stage revision in selected patients. The one-stage exchange might be considered in patients with pre-operative negative cultures in presence of ASA > 3 and multiple comorbidities that are not able to tolerate multiple surgeries.

Decreased serum superoxide dismutase concentration has a high value for the diagnosis of periprosthetic joint infection—a single-center, retrospective study

PurposeAs the most serious complication of total knee arthroplasty (TKA), periprosthetic joint infection (PJI) often leads to disastrous consequences. An accurate preoperative diagnosis plays a significant role in saving prostheses and optimizing treatment outcomes. Through this retrospective case–control study, we aimed to investigate the potential of superoxide dismutase (SOD) as a novel serum biomarker in the diagnosis of PJI.MethodsWe conducted a retrospective review of all patients who underwent TKA and received adequate follow-ups in our hospital from June 2015 to December 2021. A total of 50 patients were enrolled in the PJI group based on the 2018 International Consensus Meeting (ICM) criteria. Besides that, we enrolled 100 patients who underwent TKA in the same period and had a good postoperative course in the control group. Patient characteristics, comorbidities, laboratory results (serum, synovial, and microbial), and intraoperative findings (purulence and histopathology) were documented and compared by univariate analysis. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity, specificity, and diagnostic performance.ResultsThe median serum SOD level in the PJI and control group was 135.95 ± 24.47 U/ml (IQR, 111.85–158.30 U/ml) and 173.83 ± 13.9 U/ml (IQR,162.83–183.5 U/ml) (p < 0.05), respectively. With the calculated cutoff of SOD at 149.5U/L, the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were 0.919, 0.72, 0.97, 0.923, and 0.874, respectively. In subgroup analysis, the specificity of SOD in diagnosing culture-negative PJI remained extremely high (0.98). Combined diagnosis of serum SOD and C-reactive protein (CRP) made AUC increase to 0.972.ConclusionSerum SOD showed great potential in the diagnosis of PJI.

Culture-negative Peri-prosthetic Joint Infection after Total Hip Arthroplasty Treatment Protocol and Outcomes in Acute and Chronic Cases.

The treatment of culture-negative periprosthetic joint infections (CN PJI) of the hip represents complex entities. We, as a result of this, report on 12 cases. Irrigation and debridement (I&D) with implant retention were performed in acute cases and two-stage revisions in chronic infections. Combined antibiotic therapy was administered in all cases for 12 weeks. Infection control was achieved in all patients with an infection-free rate of 100% at 7.5 years of average follow-up.

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

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. 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. 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). 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.

Limited value of coagulation parameters in diagnosing periprosthetic joint infection.

Exploring biomarkers for easy and reliable diagnosis of periprosthetic joint infection (PJI) has attracted an increasingattention. Coagulation parameters have been found to be associated with infections, but their role in diagnosing PJI is not well understood. The aim of this study was to explore the diagnostic value of coagulation parameters in PJI. We retrospectively recruited patients who underwent revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) from January 2014 to December 2020. Patients were grouped into PJIs or non-PJIs, and PJIs were further divided into culture positive and culture negative groups. The diagnostic value of coagulation parameters including fibrin degradation product (FDP), D-dimer, platelet count (PC), and platelet count to mean platelet volume ratio (PVR) was evaluated by using receiver operating characteristic curve, in comparison with traditional biomarkers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A total of 186 patients including 136 THA and 50 TKA were studied. There were 105 PJI and 81 non-PJI patients. The coagulation parameters showed an inferior performance to CRP and ESR, with the area under the curve (AUC) of FDP, D-dimer, PC, PVR, CRP, and ESR being 0.805, 0.571, 0.703, 0.704, 0.882, and 0.824, respectively. The diagnostic performance of those coagulation parameters was similar in THA and TKA PJIs and was not superior to ESR or CRP in either culture-positive or culture-negative PJIs. Coagulation parameters FDP, D-dimer, PC, and PVR are of limited value for the diagnosis of periprosthetic joint infection in both THA and TKA patients.

An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing: A Multicenter Study.

The challenges of culture-negative periprosthetic joint infection (PJI) have led to the emergence of molecular methods of pathogen identification, including next-generation sequencing (NGS). While its increased sensitivity compared with traditional culture techniques is well documented, it is not fully known which organisms could be expected to be detected with use of NGS. The aim of this study was to describe the NGS profile of culture-negative PJI. Patients undergoing revision hip or knee arthroplasty from June 2016 to August 2020 at 14 institutions were prospectively recruited. Patients meeting International Consensus Meeting (ICM) criteria for PJI were included in this study. Intraoperative samples were obtained and concurrently sent for both routine culture and NGS. Patients for whom NGS was positive and standard culture was negative were included in our analysis. The overall cohort included 301 patients who met the ICM criteria for PJI. Of these patients, 85 (28.2%) were culture-negative. A pathogen could be identified by NGS in 56 (65.9%) of these culture-negative patients. Seventeen species were identified as common based on a study-wide incidence threshold of 5%. NGS revealed a polymicrobial infection in 91.1% of culture-negative PJI cases, with the set of common species contributing to 82.4% of polymicrobial profiles. Escherichia coli, Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus ranked highest in terms of incidence and study-wide mean relative abundance and were most frequently the dominant organism when occurring in polymicrobial infections. NGS provides a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture. Examining the profile of PJI in a multicenter cohort using NGS, this study demonstrated that approximately two-thirds of culture-negative PJIs had identifiable opportunistically pathogenic organisms, and furthermore, the majority of infections were polymicrobial. Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.