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Invasive fungal disease (IFD) is a life-threatening condition, especially in immunocompromised children. The role of diagnostic imaging in children at risk for an IFD is multifactorial, including initially detecting it, evaluating for dissemination of infection beyond the primary site of disease, monitoring the response to antifungal therapy, and assessing for potential relapse. The objective of this review was to synthesize the published literature relevant to the use of various imaging modalities for the diagnosis and management of IFD in children.

Background: We aimed to evaluate the relevance of dual target real-time polymerase chain (PCR) assays targeting the rtxA and cpn60 genes of the paediatric pathogen Kingella kingae. We also studied for the first time the clinical and epidemiological features of K. kingae infections in a Danish population. Method: Children with K. kingae-positive cultures were identified from 11,477 children and 86 children younger than 16 years old from whom blood cultures and joint fluid cultures were obtained between January 2010 and November 2016. Results were then compared to microbiological results obtained from 29 joint fluids (28 children) tested by dual target K. kingae real-time PCR from September 2014 to November 2016. Epidemiological data of all children with microbiologically confirmed K. kingae infections were collected. Results: From 2010 to 2016, we diagnosed 17 children with microbiological-proven K. kingae infections. During this period, blood cultures from five children and joint fluid cultures from a single child yielded K. kingae. Dual target K. kingae real-time PCR allowed us to increase the diagnostic yield of K. kingae infections by detecting the organism in 12 of 29 (41.4%) specimens. Notably, the 12 real-time PCR-positive specimens were rtxA-positive whereas only 10 (83.3%) were cpn60-positive. PCR-positive children were significantly younger than PCR-negative children (p-value: .01). A significant seasonal variation was found for patients with proven K. kingae infection (p-value: Conclusion: Dual target-specific real-time PCR markedly improved the detection of K. kingae in clinical specimens when compared to culture methods.

Infection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast‑like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts.

Although less common as causes of musculoskeletal infection than pyogenic bacteria, both Mycobacterium tuberculosis and nontuberculous mycobacteria can infect bones and joints. Although tuberculous arthritis and osteomyelitis have been recognized for millennia, infections caused by nontuberculous mycobacteria are being identified more often, likely because of a more susceptible host population and improvements in diagnostic capabilities. Despite advances in modern medicine, mycobacterial infections of the musculoskeletal system remain particularly challenging to diagnose and manage. This article discusses clinical manifestations of musculoskeletal infections caused by Mycobacterium tuberculosis and nontuberculous mycobacteria. Pathogenesis, unique risk factors, and diagnostic and therapeutic approaches are reviewed.

This study evaluates the effect of negative pressure wound therapy with antiseptic instillation (NPWTi) in the clearance of infection and biofilm formation in an in vivo model of infected spinal implants compared to traditional treatment modalities.Five pigs underwent titanium rod implantation of their spinous processes followed by injection of 1 x 106 CFUs/100μL of methicillin-resistant Staphylococcus aureus through the fascia at each site. At 1 week postoperatively, an experimental arm of 3 pigs received NPWTi, and a control arm of 2 pigs received wet-to-dry dressings. The persistence of local infection in the experimental group was compared to the control group using tissue cultures. Biofilm development on spinal implants was evaluated using scanning electron microscopy.Mean bacterial count showed a statistical difference between the experimental and the control groups (P.05). Scanning electron microscopy revealed the presence of uniform biofilm formation across the surface of control group instrumentation, whereas the experimental group showed interrupted areas between biofilm formations.The authors concluded that NPWTi is associated with decreased bacterial load and biofilm formation compared to wet-to-dry dressings in an in vivo porcine model of infected spinal instrumentation.

Bone and joint infections (BJIs) require complex treatment strategies, including surgical procedures and prolonged antimicrobialtherapy, and are associated with significant morbidity and mortality. Multidrug-resistant micro-organisms, particularly staphylococci,represent a therapeutic challenge, with high rates of treatment failure.

The rate and severity of septic complications following joint replacement surgery and the incidence of posttraumatic infections are projected to increase at a faster pace because of a tendency to operate on high-risk patients, including older patients, patients with diabetes, and patients who are immunocompromised or have comorbidities. Musculoskeletal infections are devastating adverse events that may become life-threatening conditions. They create an additional burden on total health-care expenditures, and can lead to functional impairment, long-lasting disability, or even permanent handicap, with the inevitable social and economic burdens. The scientific community should take a more active role to draw public attention to the plight of hundreds of thousands of people across the globe who experience complications, become disabled, and, in some cases, die, and it should highlight what could be achieved if the global community takes decisive steps to improve access, early detection, and appropriate care. However, mitigating the adverse personal, clinical, and socioeconomic effects of these conditions requires increasing financial resources provided by both governments and funding organizations. Furthermore, a targeted action plan from the providers and the professional societies should be put in place so that the burden created by bone and joint infections is included in the agenda for global health-care priorities.

Infections of the spine have been a constant throughout history. At present there are infections in the spine fostered in part by the same advances in medicine: there are a lot of immunocompromised patients, the life expectancy of patients with chronic diseases is augmented and the increasing number of complex spinal surgeries can result in secondary infection. In this review the main types of infection of the spine and its treatment highlighting techniques in minimally invasive surgery are discussed. Spontaneous pyogenic and nonpyogenic spine infections as well as iatrogenic infections can be treated in a different manner depending on its extension, location and microorganism involved. We will review the use and the indication of percutaneous image-guided techniques, endoscopic and microsurgical techniques with or without use of tubular retractors. We conclude that techniques in minimally invasive surgery in spine infections are safe, effective and have benefits in morbidity of the approach and subsequent patient recovery.

A middle-aged man presented for evaluation of a mixed-density lesion of the left posterior mandible. This clinicopathologic correlation presents the radiographic, clinical, and histopathologic findings; differential diagnosis; and treatment plan for this case. The lesion was deemed to be of bacteriologic origin, likely a polymicrobial infection containing actinomycetes. Clinical care and follow-up for the patient are discussed.

International audience; Advantages of MALDI-TOF MS (MS) were evaluated for diagnosis of bone and joint infections after enrichment of synovial fluid (SF) or crushed osteoarticular samples (CSs). MS was performed after enrichment of SF or crushed osteoarticular samples CS (n = 108) in both aerobic and anaerobic vials. Extraction was performed on 113 vials (SF: n = 47; CS: n = 66), using the Sepsityper(®) kit prior identification by MS. The performances of MS, score and reproducibility results on bacterial colonies from blood agar and on pellets after enrichment in vials, were compared. MS analysis of the vial resulted in correct identification of bacteria at a species and genus level (80.5% and 92% of cases, respectively). The reproducibility was superior for aerobic Gram-positive bacteria (Staphylococci and Gram-positive bacilli: 100% colonies), as compared to aerobic Gram-negative bacilli (89.7%), anaerobes (83.3%) and Streptococcus/Enterococcus (58.8%). MS performance was significantly better for staphylococci than for streptococci on all identification parameters. For polymicrobial cultures, identification (score>1.5) of two species by MS was acceptable in 92.8% of cases. Use of MS on enrichment pellets of bone samples is an accurate, rapid and robust method for bacterial identification of clinical isolates from osteoarticular infections, except for streptococci, whose identification to species level remains difficult.

Hip disorders are common in children. Prompt diagnosis and treatment are important because of the potential complications. Symptoms are frequently nonspecific, and clinical examination can be difficult and unreliable, especially in smaller children. Therefore, imaging can be valuable. Radiography and ultrasound remain the initial imaging modalities of choice. Increasingly, magnetic resonance imaging is obtained for assessing the pediatric hip, although the long imaging time and need for sedation may limit its use in daily practice. Because of the exposure to ionizing radiation, the use of computed tomography and bone scintigraphy in children is limited to selected cases. Pediatric hip pathology varies depending on patient age. This article provides an overview of common hip pathologies in children including congenital and developmental pathologies, trauma, infectious processes, inflammatory disease, and neoplasm. The age of the child, history, and clinical examination are essential to narrow down the differential diagnosis and subsequent selection of the appropriate imaging modality.

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.

With the development of molecular biology and specific polymerase chain reaction, Kingella kingae has become the primary diagnosis of osteoarticular infections in young children. Clinical features of these osteoarticular infections are typically mild, and outcome is almost always favorable. We report a series of unusually severe cases of K. kingae osteoarticular infections.All patients with severe osteoarticular infections at presentation were reviewed retrospectively in 2 European pediatric centers. K. kingae was identified using real-time polymerase chain reaction in blood, fluid joint or osseous samples. Clinical, laboratory tests and radiographic data during hospitalization and follow-up were analyzed.Ten children (mean age 21 ± 12 months) with severe osteoarticular infections caused by K. kingae were identified between 2008 and 2011. Diagnostic delay averaged 13.2 ± 8 days. Only 1 patient was febrile at admission, and 50% children had normal C-reactive protein values (≤10 mg/dL) at presentation. Surgical treatment was performed in all cases. Intravenous antibiotic therapy by cephalosporins for an average of 8 ± 6 days was followed by oral treatment for 27 ± 6 days. Mean follow-up was 24.8 ± 9 months, and satisfactory outcomes were reported in all cases. Two patients (20%) developed a central epiphysiodesis of the proximal humerus during follow-up, but without significant clinical consequence for the moment.Because of their mild clinical features at onset, diagnosis of K. kingae osteoarticular infections can be delayed. Care should be taken for early detection and treatment of these infections because bony lytic lesions and potentially definitive growth cartilage damage can occur.

Introduction Cotrimoxazole (Sulfamethoxazole-Trimethoprim, SXT) has interesting characteristics for the treatment of bone and joint infection (BJI): a broad spectrum of activity with adequate bone diffusion and oral and intravenous formulations. However, its efficacy and safety in BJIs are poorly documented and its use remains limited. Methods We conducted a retrospective study in 2 reference centers for BJIs from 2013 to 2018 among patients treated with SXT for a BJI. Data were collected from patient's medical charts. Outcomes and adverse events were evaluated at day (D)7, D45 and D90. Results We analyzed 51 patients with a mean age of 60 ± 20 (SD) years of which 76% presented with an orthopedic device infection (ODI). Gram-negative bacilli (GNB) were involved in 47% of BJIs (n = 24). Moreover, they were often polymicrobial infections (41%). Doses of SXT ranged from 800/160mg bid (61%; n = 31) to 800/160mg tid (39%; n = 20). Median SXT treatment duration was 45 days (IQR 40-45). SXT was part of a dual therapy in 84% of patients (n = 43), associated mainly with fluoroquinolones (n = 17) or rifampicin (n = 14). Outcome was favorable at D7 in 98% (n = 50), at D45 in 88.2% (n = 45) and at D90 in 78.4% (n = 40). The second agent combined with SXT was not an independent factor of favorable outcome (p = 0.97). Adverse events were reported in 8% (n = 4) of patients, with a median of 21 days (IQR 20-30) from SXT initiation and led to discontinuation (n = 3). Conclusion SXT appears to be effective for treatment of BJIs as a salvage therapy, even in GNB or polymicrobial infection, including ODI. Further data are needed to confirm SXT efficacy as an alternative oral regimen in BJIs.

Fracture-related infections (FRIs) are among the most common complications following fracture fixation, and they have a huge economic and functional impact on patients. Because consensus guidelines with respect to prevention, diagnosis, and treatment of this major complication are scarce, delegates from different countries gathered in Philadelphia in July 2018 as part of the Second International Consensus Meeting (ICM) on Musculoskeletal Infection. This paper summarizes the discussion and recommendations from that consensus meeting, using the Delphi technique, with a focus on FRIs. A standardized definition that was based on diagnostic criteria was endorsed, which will hopefully improve reporting and research on FRIs in the future. Furthermore, this paper provides a grade of evidence (strong, moderate, limited, or consensus) for strategies and practices that prevent and treat infection. The grade of evidence is based on the quality of evidence as utilized by the American Academy of Orthopaedic Surgeons. The guidelines presented herein focus not only on the appropriate use of antibiotics, but also on practices for the timing of fracture fixation, soft-tissue coverage, and bone defect and hardware management. We hope that this summary as well as the full document by the International Consensus Group are utilized by those who are charged with musculoskeletal care internationally to optimize their management strategies for the prevention and treatment of FRIs.

Rationale: Spinal epidural abscess (SEA) is a rare condition that shows a high prevalence in immunocompromised patients. The clinical presentation of SEA includes the “classic triad” of pain, fever, and neurological dysfunction. However, these nonspecific features can lead to a high rate of misdiagnosis. SEA may lead to paralysis or even death; thus, prognosis of these patients remains unfavorable. Patient concerns: We report a case of a multilevel (T6–T12) SEA in a 22-year-old woman. Diagnosis: The patient was initially diagnosed with spinal tuberculosis at a local hospital based on a history of tuberculosis exposure, as well as radiography and computed tomography. Histopathological examination of the tissue resected during laminectomy confirmed the diagnosis of SEA in this patient. Interventions: The patient underwent multilevel laminectomy combined with long-term antibiotic therapy. Outcomes: Physical examination performed 16 months postoperatively revealed that superficial and deep sensation was restored to normal levels in the lower extremities with improvement in the patient's motor function (muscle strength 2/5). Lessons: This case report indicates that whole spine magnetic resonance imaging is warranted in patients with SEA and that prompt surgical intervention is important at symptom onset. Long-term antibiotic therapy is also essential postoperatively.

Rationale: Osteitis corresponds to a rare but potentially serious complication reported in pediatric population after the application of the Bacillus Calmette-Guerin (BCG) vaccine. In the present study, 3 clinical cases associated with this entity are reported. Patient concerns: The 1st case corresponds to a 1-year-old female patient who presented an increase in the volume of the right pelvic limb after BCG application. The second case is a 2-year-old male who began with an increase in volume, overactive gait and pain at the level of the left knee on walking that began after a trauma in the left low limb. The 3rd case corresponds to a 3-year-old patient who started with intense pain and limitation for ambulation. Diagnosis: Both the radiographical and histological studies presented data suggestive of infection by Mycobacterium tuberculosis complex, corroborated through biopsy and genotyping analysis with the isolation of Mycobacterium bovis as the causal agent. Interventions: The basic treatment scheme was based on Ethambutol, Rifampicin, Pyrazinamide, and Isoniazid. When M. bovis was typified, clarithromycin was added in the treatment. Outcomes: Osteitis secondary to BCG vaccine usually has a favorable evolution, especially in immunocompetent patients. Lessons: It was possible to confirm the association of BCG vaccine with the clinical picture of the patients who presented improvement after the start of antimicrobial management. Osteitis secondary to BCG vaccine usually presents a favorable evolution, especially in immunocompetent patients; however, the involvement of joint, growth discs and vertebrae increases the risk of presenting long-term sequels.

We report a case of nosocomial mediastinitis and sternal osteitis due to M. hominis after open-heart surgery in an immuno-competent patient. This infection has been diagnosed by incubating the culture media for an extended period of time, and sequencing 16S rDNA directly from the clinical samples.

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case-control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25-90), and 40 (67 %) were male. Most patients had osteomyelitis (82 %), predominantly from a contiguous source (87 %). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50 %) vs. 4 (20 %); p = 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55 %) vs. 5 (25 %); p = 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p = 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2-36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75 %) vs. 27 (68 %); p = 0.8] and 6 months [14 (70 %) vs. 23 (58 %); p = 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5 %) vs. 7 (18 %); p = 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.

Background: The surgical treatment of a fracture nonunion is complicated in the presence of infection. The purpose of the present study is to report on the utility of a standardized protocol to rule out infection in high-risk patients and to evaluate the efficacy of each component of the protocol. Methods: A single protocol of preoperative laboratory tests (white blood-cell count, C-reactive protein level, and erythrocyte sedimentation rate) and a combined white blood cell/sulfur colloid scan were performed for patients with a high risk of fracture nonunion. Infection was diagnosed on the basis of positive intraoperative cultures, evidence of gross infection at the time of the procedure, or evidence of gross infection during the immediate postoperative period. With use of infection as the end point, univariate analysis and multiple logistic regression analysis were used to compare tests. A risk stratification method was used to combine tests. Results: Ninety-three patients with ninety-five nonunions were evaluated. Thirty of the ninety-five nonunions were ultimately diagnosed as being infected. With use of a combination of elevated white blood-cell count, erythrocyte sedimentation rate, and C-reactive protein level and a positive scan, the predicted probabilities of infection associated with zero, one, two, and three positive tests were 18%, 24%, 50%, and 86%, respectively. With the elimination of the nuclear scan, the predicted probabilities for zero, one, two, and three risk factors were 20%, 19%, 56%, and 100%. Conclusions: The erythrocyte sedimentation rate and the C-reactive protein level were both independently accurate predictors of infection. Use of a risk stratification method showed that the likelihood of infection increased with each additional positive test. A combined white blood cell/sulfur colloid scan was the least predictive method of revealing infection and is not cost effective, even as part of a stratification scheme. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Summary Objective In this study we sought to assess the efficacy of a technetium-99m (Tc-99m)-labeled third-generation cephalosporin as an infection imaging agent in the accurate detection of the sites of bacterial infection in vivo. Design Ceftriaxone (CRO) was formulated into a ready-to-use single-vial cold kit with a shelf-life of over 6 months and was successfully labeled with technetium. The radiolabeled drug, Tc-99m-CRO, was subjected to the following preclinical evaluations: radiochemical purity, in vitro and in vivo stability, bacterial binding assay, and pharmacokinetic studies in animals and in human patients. Results The kit formulation exhibited excellent radiolabeling efficiency (∼99%) and high in vitro and in vivo stability. The radiolabeled drug exhibited slow blood clearance (12% at 4 h), and the high protein binding and excretion pattern of the labeled formulation mimics the reported pharmacokinetic profile of the drug alone. In the animal model, scintigraphy scans showed higher uptake of the radiopharmaceutical in infectious lesions, even at 1 h post-administration, in comparison to inflammatory lesions. The clinical evaluation of Tc-99m-labeled CRO showed a diagnostic accuracy of 83.3%, and a sensitivity and specificity of 85.2% and 77.8%, respectively. Conclusions This kit formulation has the potential for imaging bacterial infections with much higher sensitivity and specificity as compared to other Tc-99m-labeled antibiotics available as convenient ready-to-use kits in routine clinical practice.

Inflammation of the hip may be due to infectious and noninfectious causes. Furthermore, involvement is categorized based on the origin and spread to adjacent structures involving the soft tissues, the joint, and underlying bone to refine the differential diagnosis. Magnetic resonance (MR) imaging is highly effective in establishing the presence and underlying cause of inflammatory and degenerative arthropathies. This article discusses the use of MR imaging for evaluation of various inflammatory conditions of the hip, both infectious and noninfectious. The number of hip prostheses is increasing, and inflammatory conditions involving the postoperative hip is also detailed separately.

Corticosteroids have a pleiotropic mechanism of action and influence a great number of cellular functions. This does not only result in a broad therapeutic effect, but in a large number of adverse events as well. It has been shown that about 60 % of all patients with rheumatoid arthritis in Germany are receiving corticosteroids and about every fifth of them more than the equivalence of 7.5 mg prednisone per day. Already small doses increase the risk f. e. for osteoporosis or cataract, as well as for severe infections. The benefit of a treatment with low dose corticosteroids in inhibiting the radiological erosivity of the disease is low and does not outweigh the risks.

Supplemental Digital Content is available in the text, Because Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) could be an interesting tool in this context. We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone 18F-FDG PET/CT between 2009 and 2015. When positive 18F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection. One hundred sixty-seven patients benefited from 18F-FDG PET/CT. The most frequent clinical subgroup before 18F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive 18F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty-two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations. We confirmed that18F-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using 18F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis.

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 107colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects.

Bone and joint infections remain a clinical challenge with potentially serious consequences. Nevertheless there is a lack of studies with strict criteria for diagnosis and etiology. The primary aim of this study was to determine the causative agents in orthopaedic infections using strict diagnostic criteria for infection and etiology. The secondary aim was to assess the timing of post-operative infections in relation to pathogens and to compare causative bacteria in different parts of the body.A retrospective registry study of 363 consecutive cases of bone and joint infections was performed. Microbiological data on sampling and culture results were registered.Staphylococcus aureus dominated in both operated (45%) and non-operated (44%) patients, followed in frequency by coagulase-negative staphylococci (CoNS) in operated patients (11%) and beta-haemolytic streptococci in non-operated patients (16%) (p 0.001). There were no polymicrobial infections in non-surgical cases (p 0.001). For operated patients, Gram-negative bacilli were observed in 6%, almost exclusively isolated from the lower extremity. Propionibacterium spp. was the most common finding after spinal surgery. In 90/363 (25%), the agent responsible for the infection could not be defined according to the strict criteria used.S. aureus dominated as etiological agent in all bone and joint infections, including operated patient given peri-operative prophylaxis. Improved timing of antibiotic prophylaxis seen after the introduction of the Swedish national project PRISS may have changed this. The number of infections with uncertain etiology was high, stressing the importance of more studies on diagnostics, as well as strict diagnostic algorithms.

International audience; Osteoarticular iatrogenic infections may be serious and justify suitable and optimised preventive measures depending on each risk, as much in terms of mortality as of morbidity. Its appreciation has been the subject of more and more studies, which allow the importance of the problem to be better evaluated. The level of iatrogenic infections after arthroscopy is evaluated at 1 to 5‰ on a recent series of knee operations, but they may be much higher for the elbow [1] and [2]. In practice, this examination is no longer used for diagnosis as it was 10 years ago, the progress in imagery means this invasive act is no longer necessary...

International audience; The rapid identification of bacterial species involved in bone and joint infections (BJI) is an important element to optimize the diagnosis and care of patients. The aim of this study was to evaluate the usefulness of matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) for the rapid diagnosis of bone infections, directly on synovial fluid (SF) or on crushed osteoarticular samples (CS). From January to October 2013, we prospectively analyzed 111 osteoarticular samples (bone and joint samples, BJS) from 78 patients in care at the University Hospital of Rennes, France. The diagnosis procedure leading to the sample collection was linked to a suspicion of infection, inflammatory disease, arthritis, or for any bone or joint abnormalities. Standard bacteriological diagnosis and molecular biology analysis [16S rRNA polymerase chain reaction (PCR) and sequencing] were conducted. In addition, analysis by MALDI-TOF MS was performed directly on the osteoarticular samples, as soon as the amount allowed. Culture, which remains the gold standard for the diagnosis of BJI, has the highest sensitivity (85.9 %) and remains necessary to test antimicrobial susceptibility. The 16S rDNA PCR results were positive in the group with positive BJI (28.6 %) and negative in the group without infection. Direct examination remains insensitive (31.7 %) but more effective than MALDI-TOF MS directly on the sample (6.3 %). The specificity was 100 % in all cases, except for culture (74.5 %). Bacterial culture remains the gold standard, especially enrichment in blood bottles. Direct analysis of bone samples with MALDI-TOF MS is not useful, possibly due to the low inoculum of BJS

We report a case of 63-year-old male, who presented with pathological fracture of left distal humerus 3 weeks previously. The radiographic findings showed an ill-defined permeative osteolytic lesion of the left distal humerus. Incisional biopsy and debridement was done; pathological examination revealed a folded cestode larva with calcareous corpuscles in the bone and soft tissue, and increased eosinophils. IgG antibody tests for sparganosis were positive. The patient refused to have surgery for internal fixation and placement of an endoprosthesis.

This study aimed to summarize clinical experience with Kingella kingae-associated pediatric osteoarticular infections (OAIs). We reviewed 566 cases in the English literature from 2000 to June 2014. More than 80% of the patients were diagnosed between 4 months and 4 years of age, and the male to female ratio was 1.14:1. The most frequent preceding illness was upper respiratory tract infections (82%). The top 3 OAIs types were septic arthritis (73.1%), osteomyelitis (15.7%), and spondylodiscitis (5.4%), and the most affected sites of these types were knee (46%), calcaneus (20%), and L4/5 disc (70%). All cases where polymerase chain reaction (PCR) technique was used were PCR positive, no reported cases of positive cultures for K kingae with negative PCR. The duration of antibiotics use ranged from 2 to 4 weeks. Beta-lactam antibiotics were the most frequently used intravenously and orally. The clinical efficacy was favorable.

Here we present the case of a young patient with one-sided winged scapula and lyme borreliosis. This disease can be very delimitating in daily life. If non-operative treatment fails, dynamic or static stabilization of the scapula can be a therapeutic option.

Staphylococcus aureus (S. aureus) colonizing the nares, is the leading cause of hospital as well as community acquired infections. The aim of this study was to identify the S. aureus from skin, soft tissue and bone related infections and typing them on the basis of antimicrobial susceptibility profile.Clinical samples were collected from patients with skin, soft tissue and bone related infections from January to October 2013 at Chitwan Medical College Teaching Hospital, Bharatpur. The S. aureus, small colony variants and methicillin resistant strains were identified by standard microbiological methods recommended by American Society for Microbiology. Antimicrobial susceptibility testing was performed by modified Kirby-Bauer disk diffusion method.Among 333 samples processed, there was positive growth of S. aureus in 66 (19.8%) samples. Among the isolated S. aureus, 10 isolates were small colony variants of S. aureus and all the strains recovered were thymidine independent in this study. Amikacin, vancomycin and teicoplanin were found to be the most effective antibiotics. Methicillin resistance was found in 34.8% isolates of S. aureus.It can be concluded that, S. aureus is one of the causative agent of pyogenic infections and the trend of antibiotic resistant is alarmingly high and also the rate of methicillin resistant S. aureus is comparably high in this study.

International audience; Biofilms are complex communities of microorganisms embedded in an extracellular matrix and adherent to a surface. The development was described as a four-stage process leading to the formation of a mature biofilm which was resistant to immune system and antibiotic actions. In bone and joint infections (BJIs), the formation of biofilms is a leading cause of treatment failure. Here we study the capacity of 11 antibiotics commonly used in the treatment of BJIs to inhibit the biofilm formation on 29 clinical Staphylococcus aureus isolates by a new test called Antibiofilmogram(\textregistered) The minimal inhibitory concentration (MIC) and biofilm MIC (bMIC) were determined in vitro and showed similar values for clindamycin, fusidic acid, linezolid and rifampin. Reversely, daptomycin, fosfomycin, gentamicin and ofloxacin showed a bMIC distribution different from MIC with bMIC above breakpoint. Finally, cloxacillin, teicoplanin and vancomycin revealed an intermediate bMIC distribution with a strain-dependent pattern. A murine in vivo model of catheter-associated S. aureus infection was made and showed a significant reduction, but not total prevention, of catheter colonization with cloxacillin at bMIC, and no or limited reduction with cloxacillin at MIC. Antibiofilmogram(\textregistered) could be of great interest after surgical operations on contaminated prostheses and after bacteremia in order to prevent the colonization of the device.

S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (10(3), 10(5), 10(8) colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 10(3) group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 10(5) and 10(8) groups showed severe signs of osteomyelitis and a non-union rate of 83-100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical infections in orthopaedic and trauma surgery and to test specifically designed diagnostic, prevention and therapeutic strategies.

Objectives The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI).Patients and methods A retrospective, single-centre cohort study (2001-11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs).Results One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5-52.6) mg/kg/day for 9.3 (1.4-20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P=0.049). After a follow-up of 76.4 (29.6-146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P=0.006), particularly when the implant was retained (OR, 4.217; P=0.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome.Conclusions Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected.

Introduction Bone, native joint and soft tissue infections are frequently referred to orthopaedic units although their volume as a proportion of the total emergency workload has not been reported previously. Geographic and socioeconomic variation may influence their presentation. The aim of this study was to quantify the burden of such infections on the orthopaedic department in an inner city hospital, determine patient demographics and associated risk factors, and review our current utilisation of specialist services. Methods All cases involving bone, native joint and soft tissue infections admitted under or referred to the orthopaedic team throughout 2012 were reviewed retrospectively. Prosthetic joint infections were excluded. Results Almost 15% of emergency admissions and referrals were associated with bone, native joint or soft tissue infection or suspected infection. The cohort consisted of 169 patients with a mean age of 43 years (range: 1–91 years). The most common diagnosis was cellulitis/other soft tissue infection and the mean length of stay was 13 days. Two-thirds of patients (n=112, 66%) underwent an operation. Fifteen per cent of patients were carrying at least one blood borne virus, eleven per cent were alcohol dependent, fifteen per cent were using or had been using intravenous drugs and nine per cent were homeless or vulnerably housed. Conclusions This study has shown that a significant number of patients are admitted for orthopaedic care as a result of infection. These patients are relatively young, with multiple complex medical and social co-morbidities, and a long length of stay.

Total hip arthroplasty (THA) is one of the most commonly performed orthopedic surgery worldwide. Current research and development had improved the designs of modern total hip prosthesis. Although long femoral stems are widely used, short stems are thought to preserve more native host bone and optimize proximal load transfer utilized with the advent of less invasive surgery. Modular short femoral stems in THA may have versatile applicability by virtue of their unique geometry, mechanism of fixation, and modularity. In this report, we present two unique case scenarios where the use of short stems has given successful results.

Background. Despite the increasing recognition of Kingella kingae as an important pathogen of early childhood, the relative frequency and invasiveness of different strains of the organism has not been investigated. A study was conducted to determine the association of K. kingae genotypes with specific clinical syndromes and the temporal and geographic distribution of invasive clones. Methods. A collection of 181 invasive K. kingae strains, isolated between 1991 and 2012 from Israeli patients with bacteremia, skeletal system infections, or endocarditis, were typed by pulsed-field gel electrophoresis (PFGE). In addition, the correspondence between PFGE, multilocus sequence types (MLSTs), and rtxA gene sequencing results was also examined for organisms belonging to the predominant PFGE clones isolated from asymptomatic carriers and patients with invasive infections. Results. A total of 32 different K. kingae clones were identified by PFGE, of which 5 (B, H, K, N, and P) caused 72.9% of all invasive infections, and were recovered during the 21-year period from different regions of the country. Clone K was significantly associated with bacteremia, clone N with skeletal system infections, and clone P with bacterial endocarditis. Strains belonging to the same PFGE clone, either carried asymptomatically or causing different invasive infections, shared MLST complexes and exhibited identical or closely related rtxA alleles. Conclusions. Although K. kingae exhibits noteworthy genetic heterogeneity, a limited number of distinct clones cause the majority of invasive infections in Israel, exhibiting genetic stability, long-term persistence, and wide geographic dispersal. K. kingae strains also show significant association with specific clinical syndromes.

Large calvarial defects in the setting of chronic infection and limited autologous donor sites present challenging problems for the reconstructive surgeon. We report on a novel osteogenic implant as a potential calvarial reconstruction solution. Two patients with an extensive history of severe traumatic brain injury and multiple cranial operations desired delayed calvarial reconstruction subsequent to removal of infected acrylic and titanium implants. These patients underwent harvesting of cancellous femoral bone and bone marrow, which was placed between 2 layers of recombinant bone morphogenic protein 2 impregnated in acellular collagen sponges and an outer layer of sturdily pliable Vicryl mesh to create a moldable osteogenic implant construct. The construct was molded into the shape of the defect and secured with sutures to the skull surrounding the defect. The osteogenic implant showed evidence of bone formation and maintained coverage over the original calvarial defect at 26 months postoperatively as well as subjective satisfaction by both patients and the senior surgeon. This technically straightforward technique with acceptable functional and aesthetic outcomes may be useful to reconstructing selected calvarial defects.

v a Actinomyces are gram-positive, nonacid-fast, branching filamentous prokaryotic microorganisms with anaerobic or microaerophilic requirements. Actinoyces species are part of the normal flora of the ropharyngeal cavity, specifically concentrated in he tonsillar crypts, the surface of carious teeth, and he gingival pocket. Actinomycosis is rarely a athologic concern because of the organism’s low irulence and does not appear to be an opportunistic isease because there is no specific predisposition oward immunocompromised individuals. Diect trauma, tooth extraction, root canal therapy, and eriodontal or periapical abscesses compromise the ntegrity of the oral mucosa and are believed to be the ost common mechanisms of pathogenesis. The principal bacteria in humans is Actinomyces israelii, a normal inhabitant of the oral cavity. Other members of the Actinomycetaceae family that are involved in human pathogenesis include A viscosus (40%), A naeslundii (5%), A odontolyticus (2%), and A meyeri (1%). Cervicofacial actinomycosis presnts as a chronic suppurative infection that typically gnores traditional fascial planes and is associated ith multiple fistulae tracts. The granulation-type leions harbor colonies of actinomyces and other baceria and promote a significant inflammatory response n the surrounding tissues. If the disease follows a ong-term course, the inflammation leads to fibrosis nd scar tissue formation, which in turn decreases xygen perfusion and creates an anaerobic environ

We report a 47 year-old man from the State of Mato Grosso do Sul, Brazil, with unifocal tibial paracoccidioidomycosis. A radiograph showed an osteolytic lesion on the tibial middle third diaphysis. The diagnosis was confirmed by histopathologic analysis, and treatment with sulfamethoxazole and trimethoprim was started. After three months, the patient showed significant clinical improvement. Ten months after treatment, the patient showed lesion bone healing. This case describes the rare occurrence of an osteolytic lesion caused by endemic Paracoccidioides brasiliensis in Latin America.

Spinal infections represent a difficult challenge to treating clinicians. Infections in the presence of implants are even more so. In this review the literature appears to reflect a change of practice in which the aim is to retain implants if possible. The newer spinal procedures such as disc replacements pose different problems largely due to the more difficult access. The situation in the spine is more difficult than in general orthopaedics when dealing with infection due to the requirement for stability and to protect neurological function. The main thrust of management, therefore, is early diagnosis and a high index of suspicion followed by adequate if not radical management in a multidisciplinary setting. In the event prevention is better than cure and therefore consideration of the various mechanisms to avoid infection must be taken. There are some 'novel' considerations for the avoidance of infection alongside the tried and tested techniques. There are also new procedures for wound closure and the elimination of dead space.

Background Bone and joint infection in adults arises most commonly as a complication of joint replacement surgery, fracture fixation and diabetic foot infection. The associated morbidity can be devastating to patients and costs the National Health Service an estimated £20,000 to £40,000 per patient. Current standard of care in most UK centres includes a prolonged course (4–6 weeks) of intravenous antibiotics supported, if available, by an outpatient parenteral antibiotic therapy service. Intravenous therapy carries with it substantial risks and inconvenience to patients, and the antibiotic-related costs are approximately ten times that of oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes. We hypothesise that, by selecting oral agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, key outcomes in patients managed primarily with oral therapy are non-inferior to those in patients treated by intravenous therapy. Methods The OVIVA trial is a parallel group, randomised (1:1), un-blinded, non-inferiority trial conducted in thirty hospitals across the UK. Eligible participants are adults (>18 years) with a clinical syndrome consistent with a bone, joint or metalware-associated infection who have received ≤7 days of intravenous antibiotic therapy from the date of definitive surgery (or the start of planned curative therapy in patients treated without surgical intervention). Participants are randomised to receive either oral or intravenous antibiotics, selected by a specialist infection physician, for the first 6 weeks of therapy. The primary outcome measure is definite treatment failure within one year of randomisation, as assessed by a blinded endpoint committee, according to pre-defined microbiological, histological and clinical criteria. Enrolling 1,050 subjects will provide 90 % power to demonstrate non-inferiority, defined as less than 7.5 % absolute increase in treatment failure rate in patients randomised to oral therapy as compared to intravenous therapy (one-sided alpha of 0.05). Discussion If our results demonstrate non-inferiority of orally administered antibiotic therapy, this trial is likely to facilitate a dramatically improved patient experience and alleviate a substantial financial burden on healthcare services. Trial registration ISRCTN91566927 - 14/02/2013 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1098-y) contains supplementary material, which is available to authorized users.

Ancient skeletal remains can harbor unique information about past civilizations at both the morphological and molecular levels. For instance, a number of diseases manifest in bone, some of which have been confirmed through DNA analysis, verifying their presence in ancient populations. In this study, anthropological analysis of skeletal remains from the ancient Albanian city of Butrint identified individuals with severe circular lytic lesions on their thoracic and lumbar vertebrae. Differential diagnosis suggested that the lesions resulted from pathologies known to affect these skeletal regions, such as tuberculosis (TB) or brucellosis. Relevant bones of two adolescent males from the 10th to 13th century AD that displayed the lesions, along with unaffected individuals, were collected in the field. Genetic screening of the skeletal samples for TB was repeatedly negative, thus additional testing for Brucella spp.-bacteria of livestock and the causative agent of brucellosis in humans-was conducted. Two Brucella DNA markers, the IS6501 insertion element and Bcsp31 gene, amplified from the affected vertebrae and/or ribs, whereas all unaffected individuals and control samples were negative. Subsequent DNA sequencing confirmed the presence of the brucellar IS6501 insertion element. On the basis of the skeletal lesions, negative tests for TB, and positive Brucella findings, we report a confirmed occurrence of brucellosis in archaeologically recovered human bone. These findings suggest that brucellosis has been endemic to the area since at least the Middle Ages.