Irrigation and debridement for knee osteoarthritis patients with suspected infection by intra-articular injection before total knee arthroplasty: a retrospective study.

BACKGROUND: Patients suffer from knee osteoarthritis (KOA) pain may seek for intra-articular injections before total knee arthroplasty (TKA), which have a possibility of causing the joint sepsis. However, the management and clinical outcomes of these patients following TKA remain uncertain. METHODS: Patients with a history of intra-articular injection, in which a joint sepsis was suspected, were included. The patients received joint irrigation and debridement (I&D) and antibiotic treatment until serum inflammatory indicators returned to normal level before TKA. The information of joint fluid routine and culture, synovium section and culture, and serum inflammatory indicator values were collected. Range of motion, Knee Society Scores (KSS) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) were used for functional evaluations. RESULTS: A total of 17 patients with 17 knee joints were included, all with elevated C-reactive protein (CRP) levels (23.5 ± 8.7 mg/L) as well as increased number of white blood cells (WBC) in the aspiration (50.8 ± 15.3) × 109/L, but no positive cultures were found. The culture of synovium detected three positive results: two Staphylococcus epidermidis and one S. aureus. I&D treatment had no obvious effect on the functional outcomes of KOA, but alleviated the joint pain (p < 0.01). Furthermore, we found that I&D pretreatment could increase the operation time with about 10 min longer than the primary TKA (p < 0.01). With respect to TKA outcomes, I&D had a slight influence on the knee flexion (p < 0.01), but no significant difference was identified between the two groups for KSS and WOMAC (all p values > 0.05). In addition, there was no significant difference in complication rates between the two groups in the last follow-up. CONCLUSION: I&D treatment is a valuable procedure for suspected knee infection, which has a higher incidence of detecting microorganisms while does not influence the functional outcomes and complication rates of TKA. However, further larger studies are required to confirm these findings.

Association of Gut Microbiome and Vitamin D Deficiency in Knee Osteoarthritis Patients: A Pilot Study.

BACKGROUND: Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/mL). METHODS: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified, and the library was prepared and sequenced on the Illumina Miseq platform. RESULTS: The mean (±SD) age was 45.5 (±10.2) years with no defined comorbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups was observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD, while Parabacteroides, Butyricimonas and Gordonibacter were abundant in the KOA_VDD group, and Peptococcus, Intestimonas, Delftia and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labelled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. CONCLUSION: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D and knee osteoarthritis.

Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.

Rare case of Ureaplasma parvum septic arthritis in an immunocompetent patient.

Mycoplasmatacea family comprises two genera: Mycoplasma and Ureaplasma Ureaplasma parvum (previously known as U. urealyticum biovar 1) commonly colonises the urogenital tract in humans. Although Ureaplasma species have well-established pathogenicity in urogenital infections, its involvement in septic arthritis has been limited to prosthetic joint infections and immunocompromised individuals. We present a rare case of native right knee infection due to U. parvum identified using next-generation sequencing of microbial cell-free DNA testing and confirmed with PCR assays. This rare case of Ureaplasma septic arthritis was diagnosed using newer next-generation DNA sequencing diagnostic modalities and a literature review of prior cases, antibiotic coverage and antimicrobial resistance is incorporated as part of the discussion.

Characterization of native knee microorganisms using next-generation sequencing in patients undergoing primary total knee arthroplasty.

BACKGROUND: Next-generation sequencing (NGS) offers improved sensitivity compared to culture-based methods for identifying organisms from synovial joints. It remains unclear whether native microorganisms exist in a joint, and positive NGS results may be interpreted as pathologic when in fact they may represent this native microbiome. The purpose of this study was to characterize the native knee microorganism profile in patients undergoing primary total knee arthroplasty (TKA). METHODS: Forty consecutive patients with osteoarthritis undergoing primary total knee arthroplasty were enrolled prospectively. During TKA surgery but prior to arthrotomy, the native knee was aspirated and the fluid was sent for NGS analysis. Immediately after arthrotomy, four separate tissue samples were also sent for NGS analysis. All microbes identified by NGS were recorded. RESULTS: Twelve out of forty patients (30%) had at least one positive organism identified by NGS from their native knee. Of those with positive NGS results, 9/12 (75%) had more than one organism identified (range two to 11). There were no significant differences in demographics, comorbidities, or incidence of prior knee injections between the two groups. There were 48 unique organisms identified from all patients, and the average number of organisms identified by NGS was 4.6 per patient. Four sterile water controls were all negative for organisms. CONCLUSION: A proportion of patients with osteoarthritis undergoing primary total knee arthroplasty have organisms identified in their joint by NGS at the time of surgery. Organisms identified after TKA by NGS when concern for periprosthetic joint infection exists may represent the native microbiome rather than pathogenic microbes.

Identification of Cartilage Microbial DNA Signatures and Associations With Knee and Hip Osteoarthritis.

OBJECTIVE: Alterations of the gut microbiota have been implicated in many forms of arthritis, but an examination of cartilage microbial patterns has not been performed. This study was undertaken to characterize the microbial DNA profile of articular cartilage and determine changes associated with osteoarthritis (OA). METHODS: We performed 16S ribosomal RNA gene deep sequencing on eroded and intact cartilage samples from knee OA patients (n = 21 eroded and 21 intact samples) and hip OA patients (n = 34 eroded and 33 intact samples) and cadaver controls (n = 10 knee samples and 10 hip samples). Microbial DNA diversity was assessed, groups were compared, and metagenomic profiles were reconstructed. Confirmation was performed in an independent cohort by clade-specific quantitative polymerase chain reaction. Findings in human cartilage were compared to those in cartilage from OA-susceptible C57BL/6 (B6) mice and OA-resistant MRL/MpJ (MRL) mice. Germ-free B6 mouse cartilage was analyzed as a methodologic control. RESULTS: Alpha diversity was reduced in human OA versus control samples (P < 0.0001), and in hip versus knee samples (P < 0.0001). Numerous clades were different in human OA versus control samples, and similar findings were noted in comparisons of murine B6 versus MRL mice. Hip samples were microbiologically distinct from knee samples. OA microbial DNA demonstrated increased gram-negative constituents (P = 0.02). Functional analysis demonstrated increases in lipopolysaccharide production (P = 9.9 × 10-3 ), phosphatidylinositol signaling (P = 4.2 × 10-4 ), and nitrogen metabolism (P = 8 × 10-3 ) and decreases in sphingolipid metabolism (P = 7.7 × 10-4 ) associated with OA. CONCLUSION: Our study reveals a microbial DNA signature in human and mouse cartilage. Alterations in this signature, including increases in gram-negative constituents, occur during the development and progression of human OA. Furthermore, our findings indicate that strain-specific signatures exist within mouse cartilage that mirror human patterns. Further study of the establishment and potential pathogenic role of these DNA signatures is needed.

Knee septic arthritis caused by α-hemolytic Streptococcus in a patient with a recent history of knee arthroscopy: a case report.

BACKGROUND: Arthroscopic partial meniscectomy is a common procedure in orthopedic practice. Infections are uncommon complications of this procedure with an incidence rate of 0,01% - 3,4%. Staphylococcus spp are the predominant causative agents in such cases. We present a case of knee septic arthritis caused by α-hemolytic Streptococcus. CASE PRESENTATION: A 22-year-old woman diagnosed with obesity (body mass index [BMI] 35 kg/m2) but with no other major comorbidities underwent an arthroscopic selective meniscectomy with administration of intravenous cefazolin for antibiotic prophylaxis. After an uneventful period of 2 months, the patient returned with pain, fever and a discharging sinus at the site of anterolateral arthroscopic portal. Blood tests and magnetic resonance imaging revealed osteomyelitis involving the tibial plate. Cultures of synovial fluid obtained from the knee and a pharyngeal swab yielded α-hemolytic Streptococcus. Five days later, the patient underwent arthroscopic debridement with partial synovectomy. Intraoperative specimens yielded α-hemolytic Streptococcus. The patient received intravenous piperacillin/tazobactam, followed by an associative regimen of amoxicillin and clindamycin with clinical, laboratory and instrumental evidence of symptom resolution. CONCLUSION: The incidence of knee septic arthritis after arthroscopic partial meniscectomy is 0.01-3.4%. This infection is usually caused by Staphylococcus spp. and in rare cases by commensal bacteria, such as α-hemolytic streptococci, secondary to transient bacteremia. Screening of the colonized area is important to prevent possible transient bacteremia. Diagnosis is based on isolation of the causative organisms from synovial fluid cultures, and treatment comprises arthroscopic debridement with individualized systemic antibiotic therapy based on the results of an antibiogram.

Intestinal microbiome composition and its relation to joint pain and inflammation.

Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain.

Outcomes and predictors of treatment failure following two-stage total joint arthroplasty with articulating spacers for evolutive septic arthritis.

BACKGROUND: The treatment strategy for evolutive septic arthritis (SA) with coexistent degenerative joint disease is not well established. The purposes of this study were to 1) investigate treatment outcome and potential risk factors of treatment failure in patients with evolutive SA following two-stage procedure, including insertion of an antibiotic-loaded spacer at the first stage and subsequent implantation of a new prosthesis; and 2) determine the performance of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Interleukin-6 (IL-6) in predicting persisting infection at second-stage procedure. METHODS: We retrospectively reviewed 74 patients with evolutive SA of hips and knees who underwent a two-stage TJA between 2008 and 2015. The treatment success was defined according to the modified Delphi criteria and Kaplan-Meier survivorship curves were constructed to determine treatment success. A Cox regression model was performed to identify risk factors for treatment failure. Receiver operating characteristic (ROC) curves were generated to determine the prognostic value of ESR, CRP, and IL-6 in predicting persistent infection before second-stage prostheses implantation. RESULTS: Overall, the treatment success rate was 93% for hips and 100% for knees after the first-stage surgery. The treatment success rate was 89% for hips and 84% for knees after second-stage prosthesis implantation with a mean follow-up of 4.7 (range, 2.2 to 10.8) years. Older age (Hazard ratio [HR] [per 10-year increase], 1.20; 95% confidential interval [CI], 1.11 to 1.62), higher preoperative CRP level (HR [per 1-mg/dL increase], 1.15; 95% CI, 1.04 to 1.28) and resistant organism (HR, 13.96; 95% CI, 3.29 to 19.20) were associated with an increased risk of treatment failure. All serologic tests presented limited values in predicting persisting infection, with the area under ROC curve of ESR, CRP, IL-6 and combination of the three markers was 57.8, 61.6, 60.3, and 62.1%, respectively. CONCLUSIONS: Two-stage TJA is an adequate management of infection control in patients with evolutive SA. The three potential risk factors (old age, high preoperative CRP, and resistant organism profile) may predict treatment failure following a two-stage procedure for evolutive SA. Additionally, serum ESR, CRP, and IL-6 had no benefit in predicting persisting infection before second-stage prostheses implantation. These findings may be useful when treating patients with evolutive SA.

Antibiotic-impregnated articulating cement spacer maintained for 7 years in situ for two-stage primary total knee arthroplasty: a case report.

BACKGROUND: Antibiotic-impregnated articulating cement spacers can maintain interim joint motion with the potential to enhance functional status and improve patient satisfaction. Articular surfaces with cement against cement have raised concerns regarding mechanical complications and cement debris during knee motion. However, long-term clinical conditions regarding these concerns are not well addressed. CASE PRESENTATION: We report a case in which articulating cement spacers were maintained in situ for 7 years. The patient had severe left knee pain with an ankylosing knee and severe tricompartmental arthritis due to tuberculous infection. We planned to perform one- or two-stage primary total knee arthroplasty (TKA), depending on the presence of infection. Persistent osteomyelitis was found intraoperatively. The second-stage TKA was delayed on the patient's request. As the patient was satisfied with the improved knee function and pain relief after using articulating cement spacers. No symptom or sign that suggested recurrent infection or systemic toxicity was found during the 7-year follow-up. However, it seemed that the bone loss progressed insidiously. At the 7-year follow-up, a broken articulating cement spacer and medial femoral condylar fracture were found. The second-stage TKA was performed, and a considerable amount of bone loss surrounded by dense granulation tissue was observed intraoperatively. Excisional biopsy of the tissue revealed chronic foreign body reaction with infiltration of giant cells and macrophages. CONCLUSION: Although the articular spacers were maintained for 7 years without major complications, regular observation of the development and progress of bone loss was required. Surgeons should take considerable bone loss into account during conversion TKA in patients with a prolonged retention of articulating cement spacers.

Polymerase Chain Reaction-Electrospray-Time-of-Flight Mass Spectrometry Versus Culture for Bacterial Detection in Septic Arthritis and Osteoarthritis.

BACKGROUND: Preliminary studies have identified known bacterial pathogens in the knees of patients with osteoarthritis (OA) before arthroplasty. AIMS: The current study was designed to determine the incidence and types of bacteria present in the synovial fluid of native knee joints from adult patients with diagnoses of septic arthritis and OA. PATIENTS AND METHODS: Patients were enrolled between October 2010 and January 2013. Synovial fluid samples from the affected knee were collected and evaluated with both traditional microbial culture and polymerase chain reaction-electrospray ionization-time-of-flight mass spectrometry (molecular diagnostics [MDx]) to prospectively characterize the microbial content. Patients were grouped by diagnosis into one of two cohorts, those with clinical suspicion of septic arthritis (n = 44) and those undergoing primary arthroplasty of the knee for OA (n = 21). In all cases where discrepant culture and MDx results were obtained, we performed species-specific 16S rRNA fluorescence in situ hybridization (FISH) as a confirmatory test. RESULTS: MDx testing identified bacteria in 50% of the suspected septic arthritis cases and 29% of the arthroplasty cases, whereas culture detected bacteria in only 16% of the former and 0% of the latter group. The overall difference in detection rates for culture and MDx was very highly significant, p-value = 2.384 × 10-7. All of the culture-positive cases were typed as Staphylococcus aureus. Two of the septic arthritis cases were polymicrobial as was one of the OA cases by MDx. FISH testing of the specimens with discordant results supported the MDx findings in 91% (19/21) of the cases, including one case where culture detected S. aureus and MDx detected Streptococcus agalactiae. CONCLUSIONS: MDx were more sensitive than culture, as confirmed by FISH. FISH only identifies bacteria that are embedded or infiltrated within the tissue and is thus not susceptible to contamination. Not all suspected cases of septic arthritis contain bacteria, but a significant percent of patients with OA, and no signs of infection, have FISH-confirmed bacterial biofilms present in the knee.

Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians.

BACKGROUND: Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable. CASE PRESENTATION: We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe. CONCLUSIONS: Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.

A case of brucellar monoarthritis and review of the literature.

Brucellosis is a systemic infectious disease, which constitutes a public health problem in Turkey. Brucellosis has a broad spectrum of clinical manifestations. Osteoarthicular manifestations are often seen in brucellosis but most of the brucellar monoarthritis cases are reactive rather than being septic. We report a case of brucellar (septic) monoarthritis of the knee in a 74-year-old cattleman and review of the literature.

Glucosamine sulfate--environmental antibacterial activity.

We have recently showed antibacterial activity against E. coli in vitro of a trademark Mega-Gluflex-containing glucosamine sulfate (GS) and chondroitin sulfate (CS). The purpose of this study was to examine the antibacterial activity of GS as a new trademark Arthryl (Manufacturer Rottapharm Ltd, Ireland; Distributor in Israel Rafa Laboratories Ltd) in vitro. We used cabbage and chicken broths and milk (every media of 20 ml) left opened for 1 week with and without Arthryl supplements 1,500 mg, the content of one package of the medication. A similar volume (20 ml) is ingested in taking the medication. Experiments with three repeatable results were taken for consideration. Arthryl inhibited environmental bacterial colonies' growth in every media but fungi growth was not impaired. Milk stayed liquid for the whole week with supplement of the Arthryl compared with sour milk transformation without Arthryl. Sample B showed inhibitory properties of the bacterial colonies on the fungi growth. The sample with Arthryl showed progressive growth of fungi without bacterial growth after 10 days of follow up compared with bacterial growth on media without Arthryl. Glucosamine sulfate as a new trademark Arthryl has environmental antibacterial properties but does not inhibit growth of fungal colonies.

MR imaging of infectious processes of the knee.

Infectious processes about the knee can result from the hematogenous spread of infection, spread from a contiguous source, direct implantation of pathogens, and prior surgery. Soft tissues, joints, and bones can be infected by bacteria, fungi, parasites, or viruses. MR imaging is useful in identifying cellulitis, abscess, septic arthritis, and osteomyelitis. The inherent tissue contrast provided by MR imaging allows for the delineation of soft-tissue infection and osteomyelitis. Therefore, MR imaging is a useful tool in evaluating the extent of infection, and in facilitating adequate debridement and drainage. MR imaging is particularly useful in the setting of chronic posttraumatic osteomyelitis and in prior surgical procedures, such as arthroscopy, anterior cruciate ligament reconstruction, and amputation.

Invasive Streptococcus agalactiae septic arthritis as an initial presentation of tonsillar carcinoma.

Invasive group B streptococcus (GBS) infection causes substantial morbidity and mortality among adults, but only in the last three decades has the role of GBS as a serious pathogen in the nonpregnant adult been better defined. It has been found that one or more serious underlying medical conditions predisposing to infection can be identified in almost all adults with invasive GBS disease. We report a 64-year-old man who had tonsillar carcinoma presenting with right knee GBS septic arthritis. In view of the rarity of invasive GBS infections in healthy non-pregnant adults, and its association with serious underlying conditions, high case fatality rates, and the need for higher doses of penicillin used in treatment, clinicians need to exercise vigilance when dealing with this disease.