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International Journal of Infectious... Apr 2019Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several... (Review)
Review
Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.
Topics: Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Humans; Joints; Osteomyelitis
PubMed: 30772469
DOI: 10.1016/j.ijid.2019.02.005 -
Frontiers in Immunology 2022Chronic recurrent and multifocal osteomyelitis (CRMO) is a nonsporadic autoinflammatory disorder. Currently, it is diagnosed based on clinical, radiologic, pathological,... (Review)
Review
Chronic recurrent and multifocal osteomyelitis (CRMO) is a nonsporadic autoinflammatory disorder. Currently, it is diagnosed based on clinical, radiologic, pathological, and longitudinal data. Numerous aspects should be highlighted due to increased knowledge in imaging and immunology. We emphasize the use of whole-body MRI, which is a non-invasive diagnostic strategy. A literature review was carried out on longitudinal studies. Commonly, the mean age at diagnosis is 11 years, ranging between 3 and 17. The most common sites are the long bone metaphysis, particularly femoral and tibial metaphysis. In addition, the pelvis, spine, clavicle, and mandible may be involved. In long bones, the radiologic appearance can show typical structure, mixed lytic and sclerotic, sclerotic or lytic. It is frequently metaphyseal or juxta-physeal, with hyperostosis or periosteal thickening. The involvement of the vertebral skeleton is often multifocal. Therefore, whole-body MRI is essential in identifying subclinical lesions. CRMO is a polymorphic disorder in which whole-body MRI is beneficial to demonstrate subclinical edema. Vertebral collapse requires long-term monitoring.
Topics: Bone and Bones; Child; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Osteomyelitis
PubMed: 36072576
DOI: 10.3389/fimmu.2022.959575 -
Nature Communications Nov 2021Clinically, it is difficult to endow implants with excellent osteogenic ability and antibacterial activity simultaneously. Herein, the self-activating implants modified...
Clinically, it is difficult to endow implants with excellent osteogenic ability and antibacterial activity simultaneously. Herein, the self-activating implants modified with hydroxyapatite (HA)/MoS coating are designed to prevent Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infections and accelerate bone regeneration simultaneously. The electron transfer between bacteria and HA/MoS is triggered when bacteria contacted with the material. RNA sequencing data reveals that the expression level of anaerobic respiration-related genes is up-regulated and the expression level of aerobic respiration-related genes is down-regulated when bacteria adhere to the implants. HA/MoS presents a highly effective antibacterial efficacy against both S. aureus and E. coli because of bacterial respiration-activated metabolic pathway changes. Meanwhile, this coating promotes the osteoblastic differentiation of mesenchymal stem cells by altering the potentials of cell membrane and mitochondrial membrane. The proposed strategy exhibits great potential to endow implants with self-activating anti-infection performance and osteogenic ability simultaneously.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bone Regeneration; Bone and Bones; Cell Differentiation; Cell Membrane; Cell Proliferation; Cell Respiration; Communicable Diseases; Disease Models, Animal; Drug Implants; Durapatite; Electron Transport; Escherichia coli; Escherichia coli Infections; Male; Mesenchymal Stem Cells; Osteogenesis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Staphylococcus aureus; Up-Regulation
PubMed: 34824260
DOI: 10.1038/s41467-021-27217-4 -
Toxicologic Pathology Oct 2017Osteoporosis increases fracture risk, a cause of crippling morbidity and mortality. The immunoskeletal interface (ISI) is a centralization of cell and cytokine effectors... (Review)
Review
Osteoporosis increases fracture risk, a cause of crippling morbidity and mortality. The immunoskeletal interface (ISI) is a centralization of cell and cytokine effectors shared between skeletal and immune systems. Consequently, the immune system mediates powerful effects on bone turnover. Physiologically, B cells secrete osteoprotegerin (OPG), a potent anti-osteoclastogenic factor that preserves bone mass. However, activated T cells and B cells secrete pro-osteoclastogenic factors including receptor activator of Nuclear factor-kappaB (NF-kB) ligand (RANKL), Interleukin (IL)-17A, and tumor necrosis factor (TNF)-α promoting bone loss in inflammatory states such as rheumatoid arthritis. Recently, ISI disruption has been linked to osteoporosis in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), where elevated B cell RANKL and diminished OPG drive bone resorption. HIV-antiretroviral therapy paradoxically intensifies bone loss during disease reversal, as immune reconstitution produces osteoclastogenic cytokines. Interestingly, in estrogen deficiency, activated T cells secrete RANKL, TNF, and IL-17A that amplify bone resorption and contribute to postmenopausal osteoporosis. T cell-produced TNF and IL-17A further contribute to bone loss in hyperparathyroidism, while T cell production of the anabolic Wingless integration site (Wnt) ligand, Wnt10b, promotes bone formation in response to anabolic parathyroid hormone and the immunomodulatory costimulation inhibitor cytotoxic T lymphocyte-associated protein-4-IgG (abatacept). These findings provide a window into the workings of the ISI and suggest novel targets for future therapeutic interventions to reduce fracture risk.
Topics: Animals; Antiretroviral Therapy, Highly Active; Bone Remodeling; Bone Resorption; Bone and Bones; Cytokines; Estrogens; HIV Infections; Humans; Immune System; Lymphocytes; NF-kappa B; Osteoclasts; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Tumor Necrosis Factor-alpha
PubMed: 29046115
DOI: 10.1177/0192623317735316 -
Clinical Microbiology and Infection :... Jul 2020Little guidance is currently available for standardized diagnostic protocols and therapeutic recommendations for bone and joint infections (BJIs) of the hand. (Review)
Review
BACKGROUND
Little guidance is currently available for standardized diagnostic protocols and therapeutic recommendations for bone and joint infections (BJIs) of the hand.
OBJECTIVES
To summarize the available data in the scientific English-language literature on the diagnosis and treatment of native BJIs of the hand. To illustrate these concepts from a narrative point of view in areas where there is lack of evidence.
SOURCES
We performed a systematic PubMed and Internet search of studies that investigated hand BJIs in adult patients.
CONTENT
Few studies have systematically investigated and validated diagnostic concepts, classifications or surgical treatment protocols. Most concepts derive from traditional intra-institutional experience, expert opinions and extrapolations from infections in large joints and long bones. Similarly, there is no uniformly accepted infection definition of BJIs of the hand. The best-documented literature is available for microbiological findings and antibiotic treatment duration in uncomplicated native joint arthritis of the fingers. Retrospective studies and one prospective randomized trial suggest that post-surgical targeted antibiotic therapy of 2 weeks results in a microbiological cure rate of ≥88%.
IMPLICATIONS
Studies on diagnostic workup and infection definition and classification are urgently needed to compare inter-institutional outcome results and generate guidelines for the best patient care. For uncomplicated pyogenic arthritis of native joints, current evidence suggests that a 2-week course of antibiotic therapy following surgery cures the infection.
Topics: Anti-Bacterial Agents; Arthritis, Infectious; Combined Modality Therapy; Early Diagnosis; Female; Hand Bones; Hand Joints; Humans; Male; Osteomyelitis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Standard of Care
PubMed: 31917233
DOI: 10.1016/j.cmi.2019.12.007 -
Journal of Ultrasound Sep 2020The assessment of bone mainly relies on standard radiographs, CT, MRI, and bone scintigraphy depending on the anatomic region complexity and clinical scenario.... (Review)
Review
The assessment of bone mainly relies on standard radiographs, CT, MRI, and bone scintigraphy depending on the anatomic region complexity and clinical scenario. Ultrasound (US), due to different acoustic impedance between soft tissues and the bone cortex, only allows the evaluation of the bone surfaces. Nevertheless, US can be useful in the evaluation of several bone disorders affecting the limbs as a result of its tomographic capabilities and high definition. This pictorial review article summarises our clinical experience in adults and reviews the literature on US bone examination. We first present the US appearance of normal bone and the main congenital anatomic variations, after which we illustrate the US findings of a variety of bone disorders. Although US has limits in bone assessment, its analysis must be a part of every musculoskeletal US examination.
Topics: Bone Diseases; Bone and Bones; Humans; Ultrasonography
PubMed: 32419074
DOI: 10.1007/s40477-020-00477-4 -
BMC Bioinformatics 2012This work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection (mostly Staphylococcus aureus). The infection alters the...
BACKGROUND
This work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection (mostly Staphylococcus aureus). The infection alters the RANK/RANKL/OPG signalling dynamics that regulates osteoblasts and osteoclasts behaviour in bone remodelling, i.e. the resorption and mineralization activity. The infection rapidly leads to severe bone loss, necrosis of the affected portion, and it may even spread to other parts of the body. On the other hand, osteoporosis is not a bacterial infection but similarly is a defective bone pathology arising due to imbalances in the RANK/RANKL/OPG molecular pathway, and due to the progressive weakening of bone structure.
RESULTS
Since both osteoporosis and osteomyelitis cause loss of bone mass, we focused on comparing the dynamics of these diseases by means of computational models. Firstly, we performed meta-analysis on a gene expression data of normal, osteoporotic and osteomyelitis bone conditions. We mainly focused on RANKL/OPG signalling, the TNF and TNF receptor superfamilies and the NF-kB pathway. Using information from the gene expression data we estimated parameters for a novel model of osteoporosis and of osteomyelitis. Our models could be seen as a hybrid ODE and probabilistic verification modelling framework which aims at investigating the dynamics of the effects of the infection in bone remodelling. Finally we discuss different diagnostic estimators defined by formal verification techniques, in order to assess different bone pathologies (osteopenia, osteoporosis and osteomyelitis) in an effective way.
CONCLUSIONS
We present a modeling framework able to reproduce aspects of the different bone remodeling defective dynamics of osteomyelitis and osteoporosis. We report that the verification-based estimators are meaningful in the light of a feed forward between computational medicine and clinical bioinformatics.
Topics: Bone Density; Bone Remodeling; Bone and Bones; Humans; Models, Biological; NF-kappa B; Osteomyelitis; Osteoporosis; Receptors, Tumor Necrosis Factor; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Transcriptome
PubMed: 23095605
DOI: 10.1186/1471-2105-13-S14-S12 -
Microbiology Spectrum Aug 2016The use of paleomicrobiological techniques in leprosy has the potential to assist paleopathologists in many important aspects of their studies on the bones of victims,... (Review)
Review
The use of paleomicrobiological techniques in leprosy has the potential to assist paleopathologists in many important aspects of their studies on the bones of victims, solving at times diagnostic problems. With Mycobacterium leprae, because of the unique nature of the organism, these techniques can help solve problems of differential diagnosis. In cases of co-infection with Mycobacterium tuberculosis, they can also suggest a cause of death and possibly even trace the migratory patterns of people in antiquity, as well as explain changes in the rates and level of infection within populations in antiquity.
Topics: Bacteriological Techniques; Bone and Bones; Coinfection; Fossils; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Leprosy; Mycobacterium leprae; Mycobacterium tuberculosis; Paleopathology
PubMed: 27726813
DOI: 10.1128/microbiolspec.PoH-0009-2015 -
Discovery Medicine May 2011The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone... (Review)
Review
The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the "immuno-skeletal interface." Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART.
Topics: Acquired Immunodeficiency Syndrome; Aging; Antiretroviral Therapy, Highly Active; Bone Diseases, Metabolic; Bone and Bones; HIV; Humans
PubMed: 21616037
DOI: No ID Found -
Chinese Journal of Traumatology =... Dec 2020In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections.... (Review)
Review
In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Topics: Anti-Bacterial Agents; Bone and Bones; Cellular Microenvironment; Humans; Immune System; Lymphocyte Subsets; Osteitis; Osteoblasts; Osteoclasts; Staphylococcal Infections
PubMed: 32847694
DOI: 10.1016/j.cjtee.2020.05.009