Culture-negative Septic Arthritis Research Articles

Clinical characteristics of and risk factors for poor outcomes in children with bacterial culture-negative septic arthritis of the hip

BackgroundSeptic arthritis of the hip is a serious infection in children. However, blood and joint fluid cultures are often negative, which makes the diagnosis and treatment challenging. We analyzed the clinical features of children with septic arthritis of the hip with negative bacterial cultures and identified the risk factors for poor outcomes. MethodsThe clinical data of children with septic arthritis of the hip with negative bacterial cultures who were treated at our hospital from January 2010 to December 2020 were retrospectively analyzed. The clinical characteristics and outcomes of the culture-negative cohort were compared with those of children with positive bacterial cultures treated during the same period. Culture-negative patients were divided into a group with good outcomes and a group with poor outcomes. The differences between the two groups were compared. ResultsThirty-nine children with culture-negative septic arthritis of the hip were compared with 37 children with culture-positive sepsis. Compared with the culture-positive group, the culture-negative group had a significantly younger mean age and a significantly lower mean serum C-reactive protein concentration. Logistic regression analysis of culture-negative patients with good versus poor outcomes revealed that the independent risk factors for poor outcomes were an increased serum C-reactive protein concentration and prolonged time from onset to surgery. The cut-off values for predicting a poor outcome in the culture-negative group were a time from onset to surgery of greater than 21 days and a C-reactive protein concentration of greater than 23 mg/L. ConclusionsCulture-negative septic arthritis of the hip has similar clinical features to culture-positive septic arthritis of the hip and can result in sequelae of varying severity. Therefore, active anti-infective and hip drainage therapy should be performed when children present with clinical symptoms, inflammatory marker concentrations, and imaging findings that are clinically diagnostic for septic arthritis of the hip. Level of evidenceLevel II, retrospective study.

Three Episodes of Presumed Culture-Negative Septic Arthritis Following Intramuscular Antipsychotic Injections: A Case Report.

We present a male patient of low socioeconomic status and Māori ethnicity who experienced 3 episodes of presumed culture-negative septic arthritis of the native hip between ages 43 and 52 years. Each episode occurred within 3 weeks of intramuscular antipsychotic injection into the ipsilateral gluteal muscles. The right hip was involved in 2 presentations and the left hip in 1 presentation. No coexisting infection or underlying immune suppression was identified, and at follow-up 2 years after the last episode, he has no sequelae of septic arthritis. This report describes 3 episodes of presumed culture-negative septic arthritis after intramuscular antipsychotic injection.

223 Joint Aspirations for Suspected Native Septic Arthritis: A Retrospective Audit of the Diagnostic Accuracy of Aspirations and Clinical Factors Associated with a Diagnosis of Septic Arthritis

Abstract Aim This study aimed to determine the diagnostic accuracy of native joint aspirations for adult septic arthritis (SA), and to determine clinical factors associated with a positive diagnosis of SA. Method Retrospective review of adult patients (≥16yrs) undergoing a major joint aspiration at a single centre over a year period (2019) were identified. Patient demographics, clinical and biochemical data, joint aspiration details, post-aspiration diagnosis, management and patient outcomes were recorded. Culture negative SA was defined as Newman's Criteria C or D. Results There were 161 native joint aspirations identified. The rate of positive diagnosis of SA was 13.0%, (n=21), with 16 (9.9%) culture positive SA and five (3.1%) culture negative SA. The presence of organisms on gram stain, high synovial white cell count (WCC), history of fever, intravenous drug use (IVDU) and previous SA diagnosis were associated with a diagnosis of SA (all p<0.05). A history of crystal arthropathy made the diagnosis of SA less likely (p=0.025). C-reactive protein (CRP) was not statistically different in the SA and non-SA groups (Area Under Curve of ROC=0.63, p=0.55). Conclusion Joint aspiration is still the preferred diagnostic test when it comes to accurately diagnosing native joint SA. However, while synovial culture and gram stain are pending, a high index of suspicion for SA can be based on a combination of patient's presenting symptoms (history of fever), previous SA or IVDU, and a high synovial WCC. These factors can aid the decision as to whether an emergency surgical washout of the joint is indicated.

The impact of gender on the clinical presentation, management, and surgical outcomes of patients with native-joint septic arthritis.

Approximately 20 000 cases of septic arthritis (SA) occur in the U.S. yearly. We examined whether gender-related differences exist in the presentation, management, and outcomes of patients with native joint septic arthritis (NJSA). This was a retrospective study of medical files of patients aged 18 years and older admitted between 1998 and 2015 to a single tertiary care hospital and diagnosed with NJSA. All study subjects had positive synovial fluid or blood cultures and each was managed surgically. Patients' charts were reviewed for demographics, comorbidities, clinical presentations, microbiology profiles, management, and outcomes. Cases of osteomyelitis, septic bursitis, prosthetic joint, and culture-negative SA were excluded. Of 324 NJSA patients, those who were female (n = 130; 40.1%) were significantly older at presentation than males (mean age: 63.6 vs 58.3; P = .006). Prior joint pathology was more common amongst females, including osteoarthritis (20.8% vs 12.9%; P = .04) and rheumatoid arthritis (10% vs 3.6%; P = .03). Female patients had a higher frequency of hip involvement (17.7% vs 10.8%; P = .05). No differences were observed in clinical presentations, culture results, medical management, or outcomes between genders. Compared to men, women with NJSA presented at an older age and had more prior joint pathology and a higher frequency of hip involvement. These differences, however, had no significant impact on the clinical presentation, medical management, or outcomes of NJSA.

Patients with surgically treated culture-negative native joint septic arthritis have less severe disease and better outcomes

Background: Patients with culture-negative septic arthritis patients are often treated surgically but might be successfully managed medically. We compared clinical characteristics and outcomes in patients with culture negative and culture positive native joint monoarticular septic arthritis.Methods: This retrospective study included all patients age ≥18 years admitted to a single, tertiary-care hospital between 1998 and 2015 with native joint monoarticular SA and treated with antibiotics and surgery.Results: Of 306 patients, 85 had negative and 221 had positive cultures. Mean C-reactive protein (p < .01) and mean percentage of peripheral polymorphonuclear cells (p = .01) were higher in culture-positive patients who had higher intensive care unit admission rates (16.7% vs. 4.7%, respectively, [p < .01]), longer length of hospital stay (11.4 vs. 7.1 days, respectively, [p < .01]) and higher mortality rates within 30 days (0% vs. 5.5%, respectively,[p = .02]). Of culture-negative patients, 28.6% received an alternative diagnosis within one year. Logistic regression models showed that culture positive patients had an adjusted odds ratio for length of stay of 4.5 (2.69, 7.51), intensive care unit admission of 5.76 (1.31, 25.22), discharge to rehabilitation of 4.7 (2.28, 9.71) and an alternative diagnosis within one year of 0.05 (0.02, 0.15) compared to culture negative patients.Conclusion: Patients with culture-negative native joint septic arthritis had less severe disease, better outcomes and higher rates of alternative diagnosis within one year than patients with positive cultures.

THE EPIDEMIOLOGY AND CLINICAL FEATURES OF SEPTIC ARTHRITIS CASES SECONDARY TO KINGELLA KINGAE IN COMPARISON TO SEPTIC ARTHRITIS FROM OTHER PATHOGENS

Abstract BACKGROUND In Europe, Kingella kingae (Kk) is considered as a significant pathogen in osteoarticular infections (OAI) in young children. Some authors suggest that a significant portion of ‘culture negative septic arthritis’ may be secondary to the inability to isolate K. kingae using conventional methods. However, its pathogenic role and prevalence remain controversial in North America. Since 2014, in order to optimize the microbiological diagnosis of OAI, all osteo-articular specimens submitted to our laboratory for bacteriology culture were simultaneously tested with a home brew multiplex PCR assay detecting Kk, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus pneumoniae. Consequently, an important increase in Kk OAI proven cases was observed. The clinical presentation of Kk OAI comparatively to the other most common pathogens seen in paediatric OAI has yet to be described in North America. OBJECTIVES The aim of this study is to review all cases of acute septic arthritis (SA) in our institution to define the prevalence of Kk SA and to compare the clinical presentation of SA cases according to their bacterial etiology, with a deeper look at SA caused by Kk. DESIGN/METHODS We conducted a retrospective chart review of all cases of suspected SA who had a synovial fluid sample submitted for bacteriology culture and multiplex PCR analysis to our microbiology laboratory between May 2014 and May 2017. Only cases of acute SA (&lt; 1 month symptom duration prior to diagnosis) were included. Children with final diagnosis that were not of infectious origin (e.g. rheumatoid arthritis, transient synovitis, etc) were excluded. Probable SA cases were defined as cases with a clinical presentation concordant with SA without any causative bacteria identified, that have received antibiotic treatment for &gt;2 weeks. Eligible SA cases were then stratified into 4 groups according to the final microbiology diagnosis: Kk SA, S. aureus SA, “other bacteria” SA or probable SA. One-way ANOVA with Tukey’s multiple comparison test if appropriate was subsequently performed to compare demographics, clinical and biochemical data, duration of treatment and outcome between subgroups. RESULTS Of the 153 patients who submitted a synovial fluid sample, 71 met the inclusion criteria. A microorganism was found in 56 patients (79%): Kk was found in 37 cases (52%), S. aureus in 11 cases (15%), S. pyogenes in 7 patients (10%), and Salmonella in 1 patient (1%); and there were15 probable SA cases (21%). Interestingly, Kk cases were proven by PCR only in 86% (n=32/37) of cases (culture was negative). One-way ANOVA showed a significant difference in age between subgroups [F(3, 67) = 13,60, p&lt;0,0001]:patients infected by Kk were younger (M=1,50 years old, SD=0,68) than S. aureus (M=7.48, SD=4.84), “other bacteria” (M=5,86, SD=4,37) and probable SA subgroups (M=5,80, SD=4,90). The duration of fever (days) was shorter [F(3, 67) = 14,07, p=0,028] in patients with Kk (M=4,1, SD=3,3) and probable SA (M=2,9 SD=3,6) in comparison to “other bacteria” cases (M=8,8, SD=8,3). Also, maximal CRP values [F(3, 67) = 14,80, p&lt;0,0001] were lower in Kk (M=42,7, SD=38,1) and probable SA (M=36,4, SD=34,6) than in SA caused by other bacteria (M=178,5, SD=98,8). Similarly, maximal neutrophil count [F(3, 67) = 6.71, p=0,0005] was lower in Kk cases (M=5,6 SD=2,3) in comparison to those infected by other bacteria (M=11,6, SD=4,1). CONCLUSION In our institution, since the implementation of multiplex PCR testing for OA samples, Kk has become the most prevalent pathogen causing SA. Children with Kk SA appear to be younger and to have a less inflammatory clinical presentation, as shown by a shorter duration of fever, lower CRP and lower neutrophil values in comparison to cases attributable to other bacteria. Prevalence of Kk SA is probably underestimated in settings where only bacteriology culture is performed.

Clinical Features and Outcomes of Children with Culture-Negative Septic Arthritis.

Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes. We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children's Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of >50000/μL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening. We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P < .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P < .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia. The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.

Septic Arthritis of Native Joints: Are Outcomes Better with Medical or Surgical Management?

Background There is limited evidence to support medical vs. surgical management of native joint septic arthritis (SA) with no established guidelines for care. Advantages of medical (antibiotics with or without serial needle aspiration) and surgical (arthroscopic or arthrotomic drainage) treatments are unknown.Methods We conducted a single-center retrospective chart review of veterans diagnosed with SA over 10 years at the West Haven VA Hospital. Demographic, clinical, laboratory, imaging, and outcome data were extracted. Cases meeting inclusion criteria (positive culture or synovial fluid WBC >50,000) were stratified by surgical vs. medical management. Evaluated outcomes included joint recovery, time to recovery, sterilization of synovial fluid, duration of antibiotics, length of stay, recurrence of SA, and mortality. Odds ratios were calculated by multivariate analyses for correlation of outcomes to risk factors and to management approach taken.ResultsSixty-one cases of SA met inclusion criteria. Average age was 67, 95% of patients were men, 89% White, 11% Black, 43% diabetic, and 43% had preexisting joint disease. 69% (41/61) of cases were managed surgically. Average length of stay for surgical group was 20 days compared with 14 days for medical group (P = 0.28). Duration of antibiotics was longer in surgical group (60.3) than medical group (35.4), (P = 0.09). S. aureus was the most common pathogen isolated (56%), followed by Streptococcus (11%) and gram-negative organisms (8%). Six (10%) patients had culture-negative SA. Mortality rate at 1 year was 3.2%. Full recovery of joint function at 1 year was achieved equally in both groups (P = 1.0), by 15/20 medically managed (75%) and 31/41 surgically managed (76%), with no significant differences by pathogen. Full recovery at 3 months was noted in 10/20 (50%) medically managed vs. 8/41 (19.5%) surgically managed (P = 0.02). Poor outcomes were not associated with joint location, pathogen, type of joint drainage, number of days to OR, or duration of antibiotics. Blacks had increased odds of poor outcome (OR 9.5; 95% CI 1.3–65.4).Conclusion We detected no statistically significant difference in outcomes at 12 months between patients managed medically vs. surgically for native joint septic arthritis. Full recovery at 3 months was significantly higher among the medical group.Disclosures All authors: No reported disclosures.

Epidemiology of Clostridium difficile Infection-Associated Reactive Arthritis in Children: An Underdiagnosed, Potentially Morbid Condition.

The incidence of Clostridium difficile infection has increased among children. The epidemiology of pediatric C difficile infection-associated reactive arthritis is poorly understood. To characterize the incidence, recognition, and distinguishing clinical features of pediatric C difficile infection-associated reactive arthritis among children with C difficile infection. In this cohort and nested case-control study using electronic health records from January 1, 2004, to December 31, 2013, across 3 geographically diverse pediatric health care networks, we screened for reactive arthritis among 148 children between ages 2 and 21 years with diagnostic or procedural codes suggesting musculoskeletal disease associated with C difficile diagnosis or positive testing. We identified 26 cases with acute arthritis or tenosynovitis within 4 weeks before to 12 weeks after confirmed C difficile infection with (1) no alternative explanation for arthritis and (2) negative synovial cultures (if obtained). Network-matched C difficile-infected controls without arthritis were randomly selected at the time of cohort member C difficile infections. Incidence of C difficile infection-associated reactive arthritis was calculated based on (1) pediatric source population and (2) children with C difficile infection. Characteristics of cases and controls were compared using conditional logistic regression. Based on the cases identified within the source population of the 3 hospital networks, we estimated that C difficile infection-associated reactive arthritis incidence was 5.0 cases per million person-years (95% CI, 3.0-7.8). Reactive arthritis affected 1.4% of children with C difficile infection yearly (95% CI 0.8%-2.3%). Joint symptoms began a median of 10.5 days after initial gastrointestinal symptoms, often accompanied by fever (n = 15 [58%]) or rash (n = 14 [54%]). Only 35% of cases of C difficile infection-associated reactive arthritis were correctly diagnosed by treating health care professionals (range across centers, 0%-64%). Five affected children (19%) were treated for presumed culture-negative septic hip arthritis despite having prior postantibiotic diarrhea and/or other involved joints. Compared with controls, cases of C difficile infection-associated reactive arthritis were less likely to have underlying chronic conditions (odds ratio [OR], 0.3; 95% CI, 0.1-0.8). Although all cases had community-onset C difficile infection and fewer comorbidities, they were more likely to be treated in emergency departments and/or hospitalized (OR, 7.1; 95% CI, 1.6-31.7). C difficile infection-associated reactive arthritis is an underdiagnosed, potentially morbid reactive arthritis associated with C difficile infection occasionally misdiagnosed as septic arthritis. Given the rising incidence of pediatric C difficile infections, better recognition of its associated reactive arthritis is needed.

Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children.

Differentiating between septic arthritis and Lyme disease of the knee in endemic areas can be challenging and has major implications for patient management. The purpose of this study was to identify a prediction rule to differentiate septic arthritis from Lyme disease in children presenting with knee pain and effusion. We retrospectively reviewed the records of patients younger than 18 years of age with knee effusions who underwent arthrocentesis at our institution from 2005 to 2013. Patients with either septic arthritis (positive joint fluid culture or synovial white blood-cell count of >60,000 white blood cells/mm(3) with negative Lyme titer) or Lyme disease (positive Lyme immunoglobulin G on Western blot analysis) were included. To avoid misclassification bias, undiagnosed knee effusions and joints with both a positive culture and positive Lyme titers were excluded. Historical, clinical, and laboratory data were compared between groups to identify variables for comparison. Binary logistic regression analysis was used to identify independent predictive variables. One hundred and eighty-nine patients were studied: 23 with culture-positive septic arthritis, 26 with culture-negative septic arthritis, and 140 with Lyme disease. Multivariate binary logistic regression identified pain with short arc motion, history of fever reported by the patient or a family member, C-reactive protein of >4 mg/L, and age younger than 2 years as independent predictive factors for septic arthritis. A simpler model was developed that showed that the risk of septic arthritis with none of these factors was 2%, with 1 of these factors was 18%, with 2 of these factors was 45%, with 3 of these factors was 84%, or with all 4 of these factors was 100%. Although septic arthritis of the knee and Lyme monoarthritis share common features that can make them difficult to distinguish clinically, the presence of pain with short arc motion, C-reactive protein of >4.0 mg/L, patient-reported history of fever, and age younger than 2 years were independent predictive factors of septic arthritis in pediatric patients. The more factors that are present, the higher the risk of having septic arthritis. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Polymerase chain reaction detection of Kingella kingae in children with culture-negative septic arthritis in eastern Ontario.

The bacterium Kingella kingae may be an under-recognized cause of septic arthritis in Canadian children because it is difficult to grow in culture and best detected using molecular methods. To determine whether K kingae is present in culture-negative joint fluid specimens from children in eastern Ontario using polymerase chain reaction (PCR) detection methods. K kingae PCR testing was performed using residual bacterial culture-negative joint fluid collected from 2010 to 2013 at a children's hospital in Ottawa, Ontario. The clinical features of children with infections caused by K kingae were compared with those of children with infections caused by the 'typical' septic arthritis bacteria, Staphylococcus aureus and Streptococcus pyogenes. A total of 50 joint fluid specimens were submitted over the study period. Ten were culture-positive, eight for S aureus and two for S pyogenes. Residual joint fluid was available for 27 of the 40 culture-negative specimens and K kingae was detected using PCR in seven (25.93%) of these samples. Children with K kingae were significantly younger (median age 1.7 versus 11.3 years; P=0.01) and had lower C-reactive protein levels (median 23.8 mg/L versus 117.6. mg/L; P=0.01) than those infected with other bacteria. K kingae was frequently detected using PCR in culture-negative joint fluid specimens from children in eastern Ontario. K kingae PCR testing of culture-negative joint samples in children appears to be warranted.

The Clinical Usefulness of Polymerase Chain Reaction as a Supplemental Diagnostic Tool in the Evaluation and the Treatment of Children With Septic Arthritis.

Culture-negative septic arthritis occurs frequently in children. The supplemental use of polymerase chain reaction (PCR) techniques improves the detection of bacteria in the joint fluid. This study evaluates the clinical utility of PCR at a tertiary pediatric medical center. Children with septic arthritis were studied prospectively from 2012 to 2014. Culture results and clinical infection parameters were recorded. PCR was performed whenever sufficient fluid was available from the joint aspiration. A statistical comparison was made for the rates of identification of the causative organism by these methods. A subgroup analysis was performed to assess the correspondence of clinical and laboratory parameters with the results of joint fluid culture and PCR. Ninety-nine children with septic arthritis were enrolled consecutively. A broad range of parameter results was identified among these children with an average of 3.6 of 6 parameters per child that met thresholds of infection. Joint fluid cultures were positive in 34 of 97 (35.1%) children from whom they were sent. Among the 68 children from whom the material was sent for PCR, the result was positive in 32 (47.1%). The combination of blood culture, joint fluid culture, and PCR resulted in bacterial detection in 49 of 97 (50.5%) children. PCR improved the rate of detection of Kingella kingae markedly when compared with joint fluid culture. PCR results were available at an average of 14.6 days after the acquisition of joint fluid. 16S PCR results were reported at an average of 17.5 days, whereas Kingella PCR took 5.1 days. PCR provides supplemental information for diagnostic confirmation through an increased rate of detection of bacteria. The timing of results and the inability to provide antibiotic sensitivity are factors that limit its clinical usefulness currently.

Role of Newman’s classification in predicting outcomes in patients with crystal arthritis

The aim of the study was to evaluate the utility of Newman's classification in predicting outcomes in patients presenting with crystal arthritis. Between January and December 2009, all patients who presented to our institution with acute crystal arthritis and were investigated with microbiological assessment of their synovial fluid were included in the study. Patients were divided into two groups depending on the fulfilment of Newman's criteria for culture-negative septic arthritis. Group 1 included patients that fulfilled Newman's B criteria. Group 2 included patients that fulfilled Newman's C criteria. A database looking at the demographics, mode of presentation, investigations, treatment and outcomes was then established and the results compared between the two groups. A total of 58 patients were identified (group 1: n = 13; group 2: n = 45). The average age was 71years (range 33-96). The joint most commonly involved was the knee followed by the wrist. Clinical findings at presentation were comparable in both groups; however, WBC and C-reactive protein (CRP) were more likely to be raised in group 1. Although most patients in group 1 were treated with antibiotics (62%) there was still a higher rate of morbidity, greater use of supportive therapy and a longer hospital stay (22.3days, SD 17.4) in comparison with group 2, where most patients were treated by observation only (76%, mean hospital stay 3.5days, SD ± 4.4). The difference in length of hospital stay was statistically significant (p < 0.0001). Newman's criteria are a good indicator for prognosis in patients with crystal arthritis. However, the presence of crystals in an acutely inflamed joint does not exclude the need for supportive therapy and long hospital stay even in the absence of positive synovial fluid culture.

Mycoplasma pneumoniae Periprosthetic Joint Infection Identified by 16S Ribosomal RNA Gene Amplification and Sequencing

Chronic, culture-negative septic arthritis represents a major clinical dilemma. It often results in prolonged courses of antimicrobial therapy, which may or may not have activity against the organism responsible for the infection. It is not possible to cultivate all types of pathogens in vitro with use of traditional laboratory testing methods, but emerging techniques can be helpful to define the etiology of these infections in some cases. We describe a case of a periprosthetic joint infection in a thirty-year-old woman with juvenile rheumatoid arthritis (JRA) and hypogammaglobulinemia, who developed septic arthritis after prolonged pneumonia. She received multiple courses of antimicrobial therapy without improvement of the joint symptoms. The microbiologic diagnosis was made with use of 16S ribosomal RNA (rRNA) gene amplification and sequencing from synovial fluid and tissue. The patient gave permission for this information to be submitted for publication. A thirty-year-old woman with JRA and hypogammaglobulinemia was referred for evaluation of an infection at the site of a total knee arthroplasty. Her JRA had been managed with multiple courses of corticosteroids, infliximab, and, more recently, rituximab. She had undergone bilateral shoulder and knee synovectomy, and right elbow synovectomy, and finally had required left total knee arthroplasty in 2006. In the fall of 2009, the patient was hospitalized because of pneumonia, which had a prolonged course, with several hospitalizations due to recurrences over two months. Chest radiographs confirmed right upper lobe pneumonia, which later progressed to bilateral pneumonia. She was treated with azithromycin and ceftriaxone and initially showed improvement, but she then had a relapse with recurrent symptoms. During the multiple relapses, she was treated with vancomycin and cefepime followed by ertapenem. She had five bronchoscopy procedures. The bronchoscopies all showed purulent secretions, but all cultures were negative, including fungal and mycobacterial cultures. Polymerase chain reaction (PCR) for Mycoplasma pneumoniae …

Rat bite fever as a presenting illness in a patient with AIDS

The etiology of culture-negative septic arthritis is poorly characterised in persons infected with human immunodeficiency virus (HIV). New molecular methods may assist in the investigation of culture-negative infections of sterile sites, including septic arthritis. We describe the first case of septic arthritis due to the cause of rat bite fever (RBF), Streptobacillus moniliformis, confirmed by 16S rRNA sequence analysis, in a patient with newly diagnosed HIV infection.

Safety, Tolerability, and Clinical Outcomes after Intraarticular Injection of a Recombinant Adeno-associated Vector Containing a Tumor Necrosis Factor Antagonist Gene: Results of a Phase 1/2 Study

To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. In this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 x 10(11), 1 x 10(12), or 1 x 10(13) DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12-30 weeks later, depending on when the target joint met predetermined criteria for reinjection. 127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14). IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.

Chronic sternal osteomyelitis complicating primary manubriosternal septic arthritis

We present a 40-year-old woman complaining of worsening chest pain. She was previously treated with a prolonged course of antibiotics for suspected sternal osteomyelitis. Radiological investigations were suggestive of ongoing inflammation within the manubriosternal joint. Formal surgical debridement yielded evidence corroborating the diagnosis although microbiological samples were negative. Prolonged empirical treatment with intravenous antibiotics leads to a complete resolution of symptoms. Primary culture-negative manubriosternal septic arthritis is rare, and suboptimal treatment, particularly if confused with other conditions such as synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome, compounds its considerable morbidity.

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.