Skeletal infections: microbial pathogenesis, immunity and clinical management

Masters, Elysia A.; Ricciardi, Benjamin F.; Bentley, Karen L. de Mesy; Moriarty, T. Fintan; Schwarz, Edward M.; Muthukrishnan, Gowrishankar

doi:10.1038/s41579-022-00686-0

Cited by 735Orthopedic Infections and TreatmentsAntimicrobial Resistance in StaphylococcusInfectious Diseases and Tuberculosis

Skeletal infections: microbial pathogenesis, immunity and clinical management

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Masters, Elysia A., Ricciardi, Benjamin F., Bentley, Karen L. de Mesy, Moriarty, T. Fintan, Schwarz, Edward M., Muthukrishnan, Gowrishankar·2022·Nature Reviews Microbiology

DOI 10.1038/s41579-022-00686-0PMC PMC8852989

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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. 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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Infected bone defects pose an arduous orthopedic healthcare challenge due to resilient biofilms and intracellular pathogens, an immunosuppressive microenvironment that impairs bone regeneration, and large defects that are difficult to heal following surgical debridement.
“Infected bone defects (IBDs) pose an arduous orthopedic healthcare challenge due to their complex pathophysiology: resilient biofilms and intracellular pathogens that evade conventional antibiotics, an immunosuppressive microenvironment that impairs bone regeneration, and large defects that are difficult to heal following surgical debridement [1,2].”
From Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects (2026) · cites this paper as [1]
The Biofilm formation and Intracellular infection sections describe hard-to-eradicate biofilms and intracellular S. aureus persistence; the immune-response section also describes suppression that enables bacterial persistence. The treatment discussion mentions debridement and large bone defects, but our copy does not establish that an immunosuppressive microenvironment impairs bone regeneration or that large defects are difficult to heal specifically after debridement. Page numbers were not available in the indexed passages. (LLM, conf=0.87)
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Bio‐inspired self‐renewing implant surfaces with sequential biofunctional adaptation for infectious diabetic tissue repair
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“In orthopedics, implant-centered infections pose arduous clinical challenges such as persistent inflammation and compromised osseoin-tegration, often culminating in implantation failure [1,27].”
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Utility of 99mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection
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IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes
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Osteomyelitis of the Long Bones
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SA-7 Os Humerus Amputation in Cat with Osteomyelitis
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Authors: Masters, E. A., Ricciardi, B. F., Bentley, K. L. D. M., Moriarty, T. F., Schwarz, E. M., & Muthukrishnan, G.
Affiliations: University of Rochester Medicine (US)
AO Foundation (CH)
Corresponding author: Schwarz, Edward M.
ORCID: Masters, Elysia A.
Ricciardi, Benjamin F.
Bentley, Karen L. de Mesy
Moriarty, T. Fintan
Schwarz, Edward M.
Muthukrishnan, Gowrishankar
Venue: Nature Reviews Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2022-02-15
Volume: 20
Issue: 7
Pages: 385-400
ISSN: 1740-1526 (ISSN-L)
1740-1534
DOI: 10.1038/s41579-022-00686-0
PMC: PMC8852989
OpenAlex: W4212885218
Semantic Scholar: fea546c64bde2b8b3e8f7ba8b09894e8cabde064
Cited by: 735
References: 213
Citations by year: 2026: 190 · 2025: 226 · 2024: 171 · 2023: 104 · 2022: 42 · 2016: 1
FWCI: 32.37
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Microbiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: AO Foundation
National Institutes of Health (AR069655, AR072000)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR072000, AR069655, P50AR072000, P30AR069655)
Topics: Health Sciences › Medicine › Surgery › Orthopedic Infections and Treatments
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords: osteomyelitis, skeletal infection, Staphylococcus aureus, implant-associated infection, biofilm, immune evasion, bacterial persistence, host immune response, orthopedic implants
MeSH terms: Humans, Osteomyelitis, Staphylococcal Infections, Staphylococcus aureus, Biofilms, Immune Evasion

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