Cutibacterium acnes and the shoulder microbiome.

BACKGROUND: Advances in DNA sequencing technologies have made it possible to detect microbial genome sequences (microbiomes) within tissues once thought to be sterile. We used this approach to gain insights into the likely sources of Cutibacterium acnes (formerly Propionibacterium acnes) infections within the shoulder. METHODS: Tissue samples were collected from the skin, subcutaneous fat, anterior supraspinatus tendon, middle glenohumeral ligament, and humeral head cartilage of 23 patients (14 male and 9 female patients) during primary arthroplasty surgery. Total DNA was extracted and microbial 16S ribosomal RNA sequencing was performed using an Illumina MiSeq system. Data analysis software was used to generate operational taxonomic units for quantitative and statistical analyses. RESULTS: After stringent removal of contamination, genomic DNA from various Acinetobacter species and from the Oxalobacteraceae family was identified in 74% of rotator cuff tendon tissue samples. C acnes DNA was detected in the skin of 1 male patient but not in any other shoulder tissues. CONCLUSION: Our findings indicate the presence of a low-abundance microbiome in the rotator cuff and, potentially, in other shoulder tissues. The absence of C acnes DNA in all shoulder tissues assessed other than the skin is consistent with the hypothesis that C acnes infections are derived from skin contamination during surgery and not from opportunistic expansion of a resident C acnes population in the shoulder joint.

Is overcorrection preferable for repair of degenerated articular cartilage after open-wedge high tibial osteotomy?

PURPOSE: This study was performed to determine whether the overcorrected knee could obtain a higher ratio of articular cartilage repair in the medial compartment of the femorotibial joint after open-wedge high tibial osteotomy (HTO). The hypothesis of the study was that overcorrected knees had a higher ratio of articular cartilage repair than moderately corrected knees. METHODS: A total of 71 knees that underwent arthroscopy to evaluate the articular cartilage during open-wedge HTO and second-look arthroscopy were reviewed. The articular cartilage was classified as no repair or repair according to Koshino et al. Overcorrection was defined as knees with femorotibial angle ≤166°. RESULTS: Second-look arthroscopy was performed 410 ± 64 days after HTO. Based on arthroscopic observations, 45 knees (63.4 %) showed no repair and 26 knees (36.6 %) showed repair. In terms of the ratio of cartilage repair, there was no difference between overcorrected knees with mean femorotibial angle of 165° ± 1° and moderately corrected knees with mean femorotibial angle of 170° ± 2° (n.s.). CONCLUSIONS: No significant differences were found in the ratio of cartilage repair between overcorrected and moderately corrected knees. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

S100A4 deficiency is associated with efficient bacterial clearance and protects against joint destruction during Staphylococcal infection.

BACKGROUND: Efficient host defense mechanisms are crucial for survival in sepsis and septic arthritis. S100 proteins are reported to have proinflammatory and bactericidal properties. The aim of this study was to investigate the role of S100A4 in staphylococcal arthritis. METHODS: S100A4 knockout mice (S100A4KO) and wild-type counterparts (WT) were intravenously and intra-articularly challenged with Staphylococcus aureus strain LS-1. Clinical and morphological signs of arthritis and sepsis, phagocytosis, bone mineral density (BMD), and bone metabolism were then monitored in S100A4 and WT mice. RESULTS: S100A4KO mice had a lower bacterial load in the kidneys than WT mice (P < .05) but developed more severe clinical signs of arthritis (P < .001) and had higher levels of interleukin 6 and L-selectin (P = .002). S100A4KO mice had fewer morphological signs of synovitis and cartilage/bone destruction following intra-articular instillation of bacteria. S100A4KO mice were protected from loss of BMD and had lower levels of RANKL, MMP3, and MMP9 (P < .05). S100A4 was not bactericidal in vitro. CONCLUSIONS: In staphylococcal infection, S100A4 regulates bacterial clearance as well as systemic and local inflammatory responses.

Articular aspergillosis: case report and review of the literature.

The incidence of invasive aspergillosis is increasing due to more frequent use of immunosuppressant agents in patients with autoimmune diseases, hematological malignancies, and solid organ and hematopoietic stem cell transplants. Invasive aspergillosis most commonly affects the lungs, sinuses, and brain. Aspergillosis affecting the musculoskeletal system is rare. We describe here a case of articular aspergillosis in a febrile neutropenic patient successfully treated with voriconazole and caspofungin, and briefly review the 10 cases of articular aspergillosis that have previously been described in the literature.

Tibiotalocalcaneal arthrodesis using a supracondylar femoral nail for advanced tuberculous arthritis of the ankle.

PURPOSE: To review 7 patients with advanced osteoarticular tuberculous arthritis of the ankle who underwent arthrodesis using a supracondylar femoral nail. METHODS: All patients showed gross destruction of the articular cartilage of the tibiotalar joint with severe periarticular rarefaction on radiographs. Their pre- and one-year post-operative Foot and Ankle Outcome Scores (FAOS) were compared. All patients underwent joint debridement, complete synovial excision, and arthrodesis using a supracondylar femoral nail, followed by multidrug chemotherapy for 12 months (isoniazid, rifampicin, pyrazinamide, and ethambutol for 3 months, and isoniazid and rifampicin for 9 months). RESULTS: All patients achieved fusion in a mean of 13 weeks and regained their preoperative level of independence. No patient had a relapse, major complications, or hardware failure. At postoperative year one, the mean FAOS for pain improved to 85 from 26, whereas the mean FAOS for quality of life improved to 60 from 5. CONCLUSION: Tibiotalocalcaneal arthrodesis using a supracondylar femoral nail, combined with debridement and multidrug therapy, enabled a reliable one-stage solution for advanced osteoarticular tuberculosis and early return to function.

Septic arthritis in Western and sub-Saharan African children - a review.

This article reviews what is known about the incidence, aetiology, presentation, bacteriology and management of septic arthritis in children. It compares where possible the different presentations and characteristics of this condition in the Western and sub-Saharan African regions.

Production of endogenous antibiotics in articular cartilage.

OBJECTIVE: Defensins are broad-spectrum antimicrobial peptides that are components of innate immunity. To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines. Infections caused by gram-negative pathogens occur only infrequently in association with joint surgery. The present study was undertaken to investigate whether this may be explained by intraarticular production of gram-negative-specialized antimicrobial peptides. METHODS: Healthy articular cartilage and cultured T/C-28a2 chondrocytes were assessed, by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, for expression of various antimicrobial peptides. The expression of human beta-defensin 2 (HBD-2) was studied in cultured chondrocytes after exposure to bacterial supernatants and proinflammatory cytokines and was assayed by real-time RT-PCR and immunoblot analysis. A septic arthritis mouse model was used to investigate the regulation of the murine homolog of HBD-2 in articular cartilage after bacterial inoculation. RESULTS: Healthy articular cartilage and T/C-28a2 chondrocytes were able to produce different antimicrobial peptides. After exposure to gram-negative bacteria and proinflammatory cytokines, expression of cartilage-derived HBD-2 strongly increased. Immunoblot analysis revealed up-regulation of the gram-negative-specialized HBD-2 in microbicidal doses. Immunohistochemistry analysis revealed induction of the murine homolog of HBD-2 in vivo after intraarticular injection of bacteria. CONCLUSION: This study demonstrated a previously unrecognized function of human chondrocytes. In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms. The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints.

Update: Unexplained deaths following knee surgery--Minnesota, 2001.

Since November 13, 2001, the Minnesota Department of Health (MDH), in collaboration with CDC, has been conducting an investigation of three patients who died unexpectedly within 1 week following knee surgery. Patient 1 had received a knee osteochondral allograft, and patients 2 and 3 had undergone total knee replacement surgery. Epidemiologic and microbiologic investigations have not linked the deaths of the three patients.

Effect of synovial membrane infection in vitro on equine synoviocytes and chondrocytes.

OBJECTIVE: To determine the functional response of synovium to infection, and the influence of infected synovium on articular cartilage metabolism. SAMPLE POPULATION: Synovium and articular cartilage explants from the midcarpal and tarsocrural joints of adult horses. PROCEDURE: For experiment 1, synovium explants were incubated as follows: control--incubation in standard medium, infected (I)--incubation with Staphylococcus aureus, and infected-filtered (IF)--incubation with medium collected from the infected group and filtered (0.22-micron filter). Daily collected medium was assayed for interleukin 1 beta (IL-1 beta), IL-6, tumor necrosis factor, and hyaluronan (HA) concentrations. For experiment 2, cartilage explants were incubated as follows: control--incubation in standard medium, and IF--incubation in medium collected from infected synovium cultures and filtered. After 48 hours, explant proteoglycan synthesis and endogenous proteoglycan and glycosaminoglycan contents were determined. RESULTS: IL-1 beta and IL-6 values were significantly increased in synovium explants from the I and IF groups. Hyaluronan concentration was lower in I and IF groups. Proteoglycan synthesis and content, and total glycosaminoglycan and chondroitin sulfate concentrations, were significantly decreased in cartilage from the IF group. CONCLUSIONS: Bacterial infection was associated with decreased HA concentration and increased mediator release. These effects were also observed despite elimination of bacteria. Exposure to sterile but previously infected medium decreased articular cartilage matrix synthesis and composition. CLINICAL RELEVANCE: Resident synovial cells may contribute appreciably to articular damage during bacterial infection in the absence of migrant inflammatory cells. This response is prolonged despite elimination of the bacteria.

Blocking of TNF-alpha and IL-1 inhibits leukocyte infiltration at early, but not at late stage of S. aureus-induced arthritis and the concomitant cartilage destruction in rabbits.

We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the pathogenesis of heat-killed S. aureus-induced arthritis. TNF-alpha and IL-1beta peaked at 2 and 24 hr after the injection, respectively. Leukocyte infiltration within 12 hr of the inflammation was significantly inhibited (80%) by coinjection of anti-TNF-alpha mAb and IL-1 receptor antagonist (IL-1Ra) with S. aureus; however, leukocyte infiltration at 24 hr and thereafter was not inhibited by these agents. The loss of proteoglycan in S. aureus-induced arthritis was also unchanged either by anti-TNF-alpha mAb, IL-1Ra, or their combination. These results indicate that direct participation of TNF-alpha and IL-1 in the pathogenesis of S. aureus-induced arthritis may be limited to the early stage of inflammation and blocking of these cytokines did not result in diminishing the severity of inflammation. Thus, therapeutic approaches with the objective to suppress TNF-alpha and IL-1 may not be effective in the clinical treatment of gram-positive bacteria-induced arthritis.

Effects of potentiated chlorhexidine on bacteria and tarsocrural joints in ponies.

OBJECTIVES: To evaluate the bactericidal properties of chlorhexidine diacetate (CHD) after potentiation with EDTA and Tris buffer (EDTA-Tris), and to find a potentiated CHD concentration that would achieve 90 to 100% killing for all bacteria tested. ANIMALS: 6 adult ponies. PROCEDURES: Serial dilutions of CHD, CHD in EDTA-Tris and EDTA-Tris alone were evaluated for bactericidal activity against Staphylococcus aureus, Escherichia coli, and Streptococcus zooepidemicus. The tarsocrural joints of 6 ponies were lavaged with either 1 L phosphate-buffered saline solution (control) or 1 L of 0.0005% CHD in EDTA-Tris. Synovial fluid was collected before lavage and on days 1,4, and 8. Synovia, cartilage, and bone with cartilage were collected on day 8 when the ponies were euthanatized. RESULTS: In vitro results indicated that 0.0005% CHD in EDTA-Tris was 90% lethal to all bacteria tested. Results of synovial fluid analysis, glycosaminoglycan analysis, and histologic examination of the synovial membrane and articular cartilage indicated that joint lavage with 0.0005% CHD in EDTA-Tris was not detrimental to the synovium or the articular cartilage of pony tarsocrural joints. Changes observed were a result of the actual lavage process, the phosphate-buffered saline solution, and hemarthrosis. CONCLUSIONS: A concentration of 0.0005% CHD in EDTA-Tris was 90% lethal to all bacteria tested. Pony tarsocrural joint lavage with 0.0005% CHD in EDTA-Tris was not detrimental to the synovium or the articular cartilage. The efficacy of 0.0005% CHD potentiated with EDTA-Tris as a potential joint lavage fluid for treatment of infectious arthritis needs to be evaluated in clinical patients.

Yersinia enterocolitica serotype 0:3-induced arthritis in mice: microbiological and histopathological information.

Gross anatomical and histopathological changes in arthritic joints resulting from oral challenge with Yersinia enterocolitica serotype 0:3, upon pretreatment with desferrioxamine, were always more severe than those induced by intravenous infection of immunized animals. In all the acute inflammation episodes studied, live Yersiniae were isolated from the arthritic region. Invariably, a heavy mixed infiltration of synovia, joint spaces and soft tissues was observed at this stage. Concurrent fibrous thickening and vascular proliferation, along with erosion of articular cartilages and anomalous bone regeneration, were also apparent. In spite of these significant facts, the bacterium could be histopathologically identified only in bone marrow where it developed microcolonies and caused significant necrosis as well. The live bacterium was also retrieved from two- and six-month-old arthritic ankles/paws examined, but it could not be seen in histological sections of joints. By this time, no cellular infiltration was evident, but there was extensive fibrosis. Bones were at times greatly enlarged, showing a spongeous-like structure. Additionally, articular cartilages could be completely lost and were substituted by an anomalous ossification filling the joint spaces. This situation led to bone fusion, resembling articular ankylosing traits. In summary, we present the first experimental evidence that Y. enterocolitica serotype 0:3 is a causal agent of osteoarthritis and osteomyelitis, and that it may survive for prolonged periods of time in osseous structures.

Differential ability of wild-type and vaccine strains of rubella virus to replicate and persist in human joint tissue.

Natural rubella has been reported to be associated with a higher incidence of arthropathy than immunisation with rubella vaccine. In addition, the different vaccines (HPV77/DE5, RA27/3, Cendehill) have been shown to vary in their association with joint symptoms in clinical trials. To investigate possible reasons for these differences in arthritogenicity, the susceptibility of human joint tissue to five rubella virus strains (three vaccines and two wt+) has been examined. Human joint tissue in either organ or dispersed cell-culture was infected in vitro and the degree of replication and persistence of each rubella strain compared. The wt+ strains (M33 and Therien) replicated to high titre in both cell and organ cultures and persisted for over 2 months. The HPV77/DE5 strain (Meruvax I) showed a very similar pattern. In contrast, the replication of RA27/3 (Meruvax II) and Cendehill (Cendevax) was highly restricted in joint cells and both of these strains showed very limited ability to penetrate and persist in the organ cultures. These results concur with the differences in arthritogenicity observed between the strains in vivo, suggesting that local viral replication may play a role in the pathogenesis of rubella-associated arthritis.

Staphylococcal adhesion to collagen in intra-articular sepsis.

Ultrastructural studies of the cartilaginous articular surfaces of human and rabbit joints have shown that cartilage is the target substratum for adhesion by Staphylococcus aureus, leading to intra-articular sepsis. Transmission and scanning electron microscope studies demonstrated bacteria in intimate contact with acellular cartilage matrix surfaces, particularly with collagen fibres. Certain strains of Staphylococcus aureus used in these experiments reveal a high binding capacity to collagen that is derived from a cartilage matrix. These studies indicate that the pathogenesis of intra-articular sepsis is based on the ability of certain strains of staphylococci to bind preferentially to a cartilage matrix.