Negative Synovial Fluid Culture Research Articles

Will Preoperative Synovial Fluid Antigen Testing Change Our Clinical Practice?

Commentary In their article, Toler et al. evaluated the diagnostic performance of a recently launched synovial fluid antigen test for the preoperative diagnosis of periprosthetic joint infection (PJI). The test is of great interest because identifying the causative microorganism prior to the surgical procedure is important in guiding surgical decision-making and starting targeted antimicrobial treatment as soon as possible. Toler et al. demonstrated a high concordance between synovial fluid culture and the antigen test. Moreover, in culture-negative synovial fluids, the test identified a microorganism in 49% of cases. However, from a clinical point of view, there are important limitations that should be taken into consideration. With regard to how the test will guide antibiotic treatment, the following shortcomings should be taken into account. A limited number of species (i.e., Staphylococcus, Enterococcus, and Candida species) are included in the test, as noted in the article, and it is important to keep in mind that the reference test used to calculate the diagnostic accuracy was a positive synovial fluid culture for the included species. A comparison with intraoperative tissue cultures was not performed, and, because the sensitivity of synovial culture is poor, an infection cannot be ruled out in the case of a negative antigen test. Therefore, empirical antibiotic treatment should still be administered in the case of a negative antigen test when a PJI is suspected. In the case of a positive test, it is important to realize that, in addition to the inclusion of a limited number of species that can be detected, the test only identifies species on a genus level. Because the antibiotic treatments for methicillin-sensitive staphylococci compared with methicillin-resistant staphylococci and for Enterococcus faecalis compared with Enterococcus faecium are different, their identification on a genus level cannot fully target antibiotic treatment. Other tests that overcome this limitation are available, such as the recently launched multiplex polymerase chain reaction (PCR) for bone and joint infections1. The BioFire Joint Infection PCR Panel provides a rapid diagnosis (i.e., within 1 hour), includes more genera and identifies pathogens on a species level, and detects resistance genes, which may better guide antimicrobial treatment1. Also, other microorganisms not detected by the PCR test may be involved. According to the literature, around 30% to 40% of PJIs are polymicrobial in nature, with an even higher incidence observed in early postoperative and chronic infections with a sinus tract2,3. Consequently, empirical antibiotic treatment cannot be easily narrowed in the case of a positive antigen test either. With regard to how the test will help us in surgical decision-making, some experts in the field have advocated a 2-stage exchange instead of 1-stage exchange for PJI caused by difficult-to-treat microorganisms such as enterococci and Candida4,5. Therefore, isolating these species prior to the surgical procedure may guide surgical decision-making. However, in the total cohort in the study by Toler et al., Candida species already grew on synovial fluid culture in 338 cases and Enterococcus species grew on culture in 465 cases. More rapid identification that the antigen provides is not needed in chronic infections, as one has time to wait for the final culture results. In the remaining preoperative samples with negative synovial fluid cultures, the antigen test detected Candida in an additional 142 cases and enterococci in an additional 188 cases. If these extra cases were to be considered to represent real infections, rather than false-positives as stated by Toler et al., only 0.3% of candidal infections and 0.4% of enterococcal infections from the total cohort of patients will have been missed when solely relying on preoperative cultures of synovial fluid. This low percentage of missed infections makes one wonder whether the number needed to test is really justified. Last but not least, Toler et al. analyze their results according to whether the preoperative diagnosis, according to the 2018 International Consensus Meeting, was positive or negative, but the inconclusive cases (7.5% of the total cohort) are not included in the final analysis, although these are the cases that are most clinically challenging. Based on the above-mentioned limitations and the way that the results are analyzed, it seems that the evaluated antigen test will not change our daily clinical practice in a large number of cases. Additional analyses, particularly comparisons with the final postoperative diagnosis and intraoperative culture results, are needed to define the role of this test in the diagnostic workup.

Retrospective evaluation of 103 cases of septic arthritis in dogs.

This study examines inciting causes, diagnosis, treatment and risk factors for the recurrence and outcome of septic arthritis (SA) in dogs. Medical records spanning 17 years from five referral hospitals were surveyed for presumptive and confirmed cases of SA. SA was identified in 103 cases. Spontaneous septic SA was the most common inciting cause. The most commonly affected joints were the stifle (40%) and elbow (24%). Pre-existing osteoarthritis (OA) was present in 63% of septic joints and was associated with recurrence (p=0.03). Treatment with antibiotics prior to presentation was associated with a negative synovial fluid culture (p=0.014). A successful outcome was associated with early treatment (p=0.001) and SA due to direct penetration (p=0.04) or spontaneous cause (p=0.003). Recurrence was more likely in dogs with unsuccessful outcomes (p=0.004) and bodyweights>30kg (p=0.009). SA should be considered as a differential diagnosis in large breed dogs with pre-existing OA presenting with either an acute or chronic monoarthropathy. In the majority of cases, a successful outcome was achieved regardless of treatment type. Recurrence rates were low, but associated with pre-existing OA and higher bodyweight. Although treatment should be implemented as soon as possible to maximise outcome success, synovial fluid samples should ideally be obtained before empiric antibiotic administration.

Clinical Presentation, Management, and Prognosis of Pseudogout in Joint Arthroplasty: A Retrospective Cohort Study.

Introduction: Calcium pyrophosphate deposition disease (CPPD), or pseudogout, is rare in prosthetic joints, but can mimic prosthetic joint infection (PJI) according to case reports. The purpose of this case series is to describe the demographics, presentation, management, and outcomes of a cohort of these patients seen at our academic medical center.Methods: Patients with post-implant pseudogout, who were evaluated at our medical center between January 1, 2000 and June 30, 2016, were identified from our EHR. Data pertaining to demographics, presentation, management, and outcomes were abstracted, and patients were categorized into two groups based on presence of concomitant infection along with positive CPDD findings in synovial fluid.Results: 22 patients were included. 90.9% of cases involved a TKA. The most common indication for arthroplasty was degenerative joint disease. Only four patients had a history of previous gout or pseudogout, three of which belonged to the group with no evidence of concomitant joint infection. Clinical features for patients without concomitant infection included pain (100%), swelling at the joint (88.9%), redness (33.3%), fever (22.2%), and decreased range of motion (100%). 45.5% of patients received antibiotics prior to joint aspiration (44.4% of patients with negative synovial fluid cultures, 46.2% of patients with concomitant infection).Conclusion: Our study suggests similar clinical presentation between post-implant pseudogout and PJI. Among patients with pseudogout as well as in those with PJI, the first dose of antibiotics should not be given before sampling for synovial culture. Unfortunately, many patients receive antibiotics prior to culture ascertainment, which raises concern for antibiotic overuse.

A55: Clostridium difficile Infection‐Associated Reactive Arthritis in a Pediatric Cohort

Background/Purpose:Clostridium difficile infection (CDI) has increased among children and is associated with significant morbidity and mortality. CDI‐associated reactive arthritis (CDIAReA) has been described in adults and a few pediatric case reports, but little is known about CDIAReA in pediatric patients.Methods:Children ages 2–20 with CDIAReA in 2004–2013 were identified within a multistate pediatric care network's electronic medical record. Administrative data were used to identify cases defined by: 1) a diagnosis code for arthritis and 2) the CDI diagnosis code and/or positive C. difficile test in any setting (ambulatory or inpatient). Records were reviewed to confirm presence of symptomatic CDI and acute arthritis and/or tenosynovitis that met the following inclusion criteria: 1) occurrence between 4 weeks before and 12 weeks after CDI diagnosis, 2) documentation by a physicianlevel provider or imaging, 3) no other cause identified, and 4) negative synovial fluid cultures (if obtained).Results:111 patients were identified for record review, and 13 met the inclusion criteria. Median age of confirmed cases was 13.2 years [range 3.4, 19.3], with similar sex distribution (6 females, 7 males). Approximately half (46%) of cases had chronic medical conditions, including 3 (23%) with autoimmune diseases, whose underlying condition did not explain their acute arthritis. Among subjects with CDIAReA, all CDIs were community‐associated and mild, except for 1 subject with preexisting lupus nephritis. Arthritis was most often migratory (85%) and polyarticular (54%) involving large and small joints, with a median of 6 affected joints [range 2, 15]. The most commonly involved joints were knees (69%) and ankles (69%) followed by wrists (62%) and elbows (54%). Eight patients (62%) experienced concurrent fever, and 9 (69%) had rash. Over half (62%) were hospitalized due to joint pain. Of these, 5 (38%) were suspected to have septic arthritis and 2 (15%) underwent surgical drainage procedures for presumed septic hip arthritis with purulent effusions (both culture‐negative). Median time from onset of gastrointestinal symptoms to resolution of joint symptoms was 30 days [range 8,76]. Symptoms generally resolved with treatment of underlying CDI and, in 69%, NSAID use. Three subjects (23%) without prior arthritis had subsequent recurrent episodes of migratory joint pain not associated with documented CDI. Aside from the primary physician, 85% were evaluated by emergency physicians, 69% by rheumatologists, 54% by inpatient pediatricians, and 46% by orthopedists. Of confirmed cases, 5 (38% [95% CI 14, 68%]) were never diagnosed with CDIAReA by their treating providers.Conclusion:CDIAReA is an under‐recognized pediatric condition characterized by a painful, migratory, often polyarticular arthritis of large and small joints in the setting of CDI. Though a self‐limited condition in this cohort, its acuity led to considerable morbidity and resource utilization, in some cases due to confusion with septic arthritis. Further research is needed to determine the incidence and risk factors for pediatric CDIAReA.

Identification of silent prosthetic joint infection: preliminary report of a prospective controlled study

PurposeWe will test the hypothesis that ultrasound supported by polymerase chain reaction (PCR) could improve bacterial identification in non-infected prosthetic joint loosening. The aim was to detect bacterial species in non-infected prosthetic joint loosening using ultrasound and 16S rRNA gene sequencing.MethodsA total of 16 patients (11 women and five men) aged 46–80 years (mean age 65.7) with diagnosed knee or hip implant loosening (mean implant survival of 102.1 months) were investigated. Bacterial culture and DNA sequencing were used to detect bacteria on the surface of failed implants removed during revision arthroplasty. The results of pre- and intraoperative culture and DNA sequencing were compared. Histopathological analysis was also performed.ResultsThe number of positive cultures rises with a higher level of C-reactive protein (CRP). The results of the cultures from synovial fluid obtained through joint aspiration were consistent with sonicates from components of prostheses in 12 cases (75 %). Bacterial DNA was found in 90 % of patients with negative synovial fluid culture. PCR revealed two or more bacterial species, often of the same genus: Ralstonia pickettii, Pseudomonas spp., Brevibacterium spp., Lactobacillus spp., Propionibacterium spp. and Staphylococcus spp.These are micro-organisms present in the environment or on the human body and often associated with compromised immunity.ConclusionsThe ultrasound procedure followed by PCR and sequencing improve bacterial identification in silent prosthetic joint infection. The lack of clinical signs of infection and negative preoperative and intraoperative cultures do not exclude the presence of micro-organisms on the implants.

THU0369 Septic arthritis: Changing trends in epidemiology over two decades

BackgroundSeptic arthritis (SA) is the most rapidly destructive joint disease. The estimated incidence of septic arthritis is 2-10 cases per 100,000 per year. The incidence of septic arthritis appears to...

How to perform and analyse synovial biopsies

Although most of the rheumatologic diseases can be diagnosed based on clinical examination combined with additional laboratory and radiographic tests, histological examination of synovial tissue may lead to the correct diagnosis and adjustment of therapy when neoplastic or granulomatous disease, deposition disease or infection in spite of negative synovial fluid culture is suspected. For research purposes synovial tissue analysis is used to investigate the pathological changes of the synovium in studies aimed at elucidating the aetiology and pathogenetic mechanisms involved in arthritis. In addition, the use of synovial biomarkers has been shown to be instrumental in the developmental process of new therapeutics. In this chapter, several minimally invasive techniques for acquiring synovial tissue samples, handling of the tissue and the analysis thereof are described.

The fate of acutely inflamed joints with a negative synovial fluid culture

The purpose of this study was to evaluate the management and fate of acutely inflamed joints with a negative synovial fluid culture. Between January and December 2009, all the patients who presented to our institution with an acutely inflamed joint and were subjected to microbiological assessment of their synovial fluid, were included in the study. Patients with a positive synovial fluid culture, a prosthetic joint replacement in situ and where an aspirate was obtained for a rheumatological diagnosis were excluded. This cohort was then divided into two groups depending on whether a diagnosis could be established through the course of their treatment. Group I included patients in whom a diagnosis could be established and group II included patients in whom a diagnosis could not be established. A thorough review of the patients' medical records and the hospital database was performed. Following this, a database consisting of the patient demographics, clinical features, investigations, treatment and outcome was created. A total of 144 patients met the inclusion criteria (group I: 95, group II: 49). The most commonly affected joint in both the groups was the knee. The average time to presentation was shorter in group II. Clinical findings at presentation were comparable in both groups. However, inflammatory markers were more likely to be raised in group II in comparison with group I. Eighty-two percent of group II required antibiotic treatment compared with 15% of group I. The mean duration of antibiotic treatment in group I was ten days and in group II was 26 days. Mean hospital stay differed significantly between the two groups, with group II being more than twice as long as compared with group I (p=0.001). The rate of mortality was also higher in group II (8.2%, p=0.03). Our study shows that patients presenting with an acutely inflamed joint and a negative synovial fluid culture in whom a diagnosis cannot be established during their hospital stay have a longer hospital stay and an increased rate of mortality as compared with patients in whom a diagnosis can be established.

How to perform and analyse synovial biopsies

Although most of the rheumatologic diseases can be diagnosed based on clinical examination combined with additional laboratory and radiographic tests, histological examination of synovial tissue may lead to the correct diagnosis and adjustment of therapy when neoplastic or granulomatous disease, deposition disease, or infection in spite of negative synovial fluid culture is suspected. For research purposes synovial tissue analysis is used to investigate the pathological changes of the synovium in studies aimed at elucidating the etiology and pathogenetic mechanisms involved in arthritis. In addition, the use of synovial biomarkers has been shown to be instrumental in the developmental process of new therapeutics. In this chapter, several minimally invasive techniques for acquiring synovial tissue samples, handling of the tissue, and the analysis thereof are described.

Recurrent episcleritis associated with brucellosis.

To document the clinical course and the treatment of episcleritis associated with brucellosis. Three consecutive cases of patients with recurrent episcleritis associated with brucellosis were evaluated through clinical and laboratory data including serology (tube agglutination), blood culture, and synovial fluid culture. All the patients had ingested contaminated milk and/or fresh cheese. The diagnosis of brucellosis was confirmed by high antibody titer, positive blood culture, negative synovial fluid culture and unresponsive condition to the previous nonspecific therapy for episcleritis and reactive arthritis. The patients responded well to the therapy with doxycycline and rifampicin. We proposed that recurrent episcleritis had a co-occurence with reactive arthritis in the course of the brucellosis, and that it responded well to the antibrucellar antibiotics rather than to steroids. This also implies that brucellosis as a rule is an underlying triggering infection associated with reactive arthritis.

Culture-Negative Septic Arthritis in Children

To compare the incidence, characteristics, treatment course, and clinical outcome of children with culture-negative versus culture-positive septic arthritis, we reviewed all 105 children treated for septic arthritis at our institution from 1990 to 1997. Seventy-six children had a clinical presentation consistent with an isolated joint infection. All underwent a joint aspiration with fluid analysis including culture. All were followed up until resolution of their symptoms. Culture of the synovial aspirates identified an etiologic organism in only 30% of cases. No significant differences existed between the culture-positive and culture-negative groups in most clinical and laboratory criteria. No other diagnoses were demonstrated. All patients underwent joint drainage, received comparable antibiotic therapy, and had complete resolution of their infections. The current literature reports deceptively low rates of 18-48% for culture-negative septic arthritis. Seventy percent of children with clinical findings of septic arthritis had negative synovial fluid cultures. As the two culture groups were comparable and no other diagnoses were demonstrated, the culture-negative cases were likely infections. Thus we recommend the same aggressive treatment in those cases with and without identification of a causative organism.