Skeletal infections: microbial pathogenesis, immunity and clinical management
Elysia A Masters1,2, Benjamin F Ricciardi1,3, Karen L de Mesy Bentley1,3,4
1Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
Abstract:
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.
Insights
Osteomyelitis, a severe bone infection often caused by Staphylococcus aureus, persists despite new insights into bacterial mechanisms. Current treatments offer limited progress, necessitating novel interventions for effective eradication.
Area of Science:
- Orthopaedic Surgery
- Infectious Diseases
- Microbiology
Background:
- Osteomyelitis poses a significant risk in orthopaedic surgery, with Staphylococcus aureus being the primary pathogen.
- Despite understanding S. aureus pathogenesis (biofilms, abscesses, osteocyte invasion), clinical treatment of skeletal infections has seen minimal advancement.
- Host immune responses are insufficient for eradicating bacterial bone infections.
Purpose of the Study:
- To review mechanisms of S. aureus persistence and immune evasion in osteomyelitis.
- To discuss other pathogens involved in bone infections and host failure in eradication.
- To explore novel interventions and current clinical management strategies for skeletal infections.
Main Methods:
- Literature review of S. aureus pathogenesis in bone.
- Analysis of host immune response failures in skeletal infections.
- Discussion of current and emerging clinical management strategies.
Main Results:
- S. aureus employs complex mechanisms for persistence within bone, including biofilms and invasion of the osteocyte network.
- Host immune systems struggle to clear bacterial bone infections effectively.
- Limited clinical progress has been made in preventing and eradicating osteomyelitis over the past 50 years.
Conclusions:
- Understanding pathogen persistence and host immune evasion is crucial for developing new osteomyelitis treatments.
- Novel interventions targeting bacterial mechanisms and enhancing host immunity are needed.
- Advancements in clinical management and emerging technologies hold promise for future skeletal infection treatment.
Related Concept Videos
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Microorganisms in Medicine and Therapeutics
Infection
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
Skin Diseases and Disorders
Gram-positive Staphylococcus spp. and Streptococcus spp. are responsible for many of the most common skin infections. However, many...
Fungal Phylum Microsporidia


