The Nobel Prize in physiology or medicine

Osteomyelitis is a devastating disease caused by microbial infection of bone While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone In contrast, S aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis There have also been major advances in our understanding of the immune proteome against S aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease Here, we review these recent advances and highlight translational opportunities towards a cure

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Evolving concepts in bone infection: redefining "biofilm", "acute vs. chronic osteomyelitis", "the immune proteome" and "local antibiotic therapy".

Forty-three patients having 49 treatment protocols for periprosthetic total joint infections were staged prospectively, using an osteomyelitis classification system designed to stratify treatment selection according to patient risk factors. Implant salvage was possible in 66% of the infections treated within 30 days of the surgical procedure or within 14 days of symptom onset after a late, septic event. After debridement and implant removal, 88% of the patients with long-standing, refractory infections now have infection-free, functional reconstructions; 64% of these patients have a new, total joint replacement at the original site of treatment. All of the treatment failures, deaths, and amputations occurred in the high-risk patient cohorts prospectively identified within the staging system. Infection duration and the condition of the host are the two most important variables in predicting outcomes in patients with periprosthetic infections.

Periprosthetic total joint infections: Staging, treatment, and outcomes : Orthopaedic infections

Antimicrobial peptides - Advances in development of therapeutic applications.

Osteomyelitis remains one of the greatest risks in orthopaedic surgery. Although many organisms are linked to skeletal infections, Staphylococcus aureus remains the most prevalent and devastating causative pathogen. Important discoveries have uncovered novel mechanisms of S. aureus pathogenesis and persistence within bone tissue, including implant-associated biofilms, abscesses and invasion of the osteocyte lacuno-canalicular network. However, little clinical progress has been made in the prevention and eradication of skeletal infection as treatment algorithms and outcomes have only incrementally changed over the past half century. In this Review, we discuss the mechanisms of persistence and immune evasion in S. aureus infection of the skeletal system as well as features of other osteomyelitis-causing pathogens in implant-associated and native bone infections. We also describe how the host fails to eradicate bacterial bone infections, and how this new information may lead to the development of novel interventions. Finally, we discuss the clinical management of skeletal infection, including osteomyelitis classification and strategies to treat skeletal infections with emerging technologies that could translate to the clinic in the future. Osteomyelitis is an infection of bone that arises when a pathogen colonizes bone tissue owing to injury or surgery. In this Review, Masters and colleagues explore the microbial pathogenesis, immunity and clinical management of bone infections. 

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Skeletal infections: microbial pathogenesis, immunity and clinical management

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.24293

Sommer Hammound

Papers

2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions