Bone and Joint Infection Involving Corynebacterium spp.: From Clinical Features to Pathophysiological Pathways

Pierre Chauvelot; Tristan Ferry; Virginie Tafani; Alan Diot; Jason Tasse; Anne Conrad; Christian Chidiac; Evelyne Braun; Sébastien Lustig; Frédéric Laurent; Florent Valour

doi:10.3389/fmed.2020.539501

Bone and Joint Infection Involving Corynebacterium spp.: From Clinical Features to Pathophysiological Pathways

Front Med (Lausanne). 2021 Jan 21:7:539501. doi: 10.3389/fmed.2020.539501. eCollection 2020.

Authors

Pierre Chauvelot^{1

2

3}, Tristan Ferry^{1

2

3}, Virginie Tafani³, Alan Diot³, Jason Tasse^{3

4}, Anne Conrad^{1

2

3}, Christian Chidiac^{1

2

3}, Evelyne Braun^{1

2}, Sébastien Lustig^{2

5}, Frédéric Laurent^{2

3

6}, Florent Valour^{1

2

3}

Affiliations

¹ Departement of Infectious Diseases, Hospices Civils de Lyon, Lyon, France.
² French Regional Reference Center for Complex Bone and Joint Infection (CRIOAc), Hospices Civils de Lyon, Lyon, France.
³ International Centre for Research in Infectiology, INSERM U1111, Claude Bernard Lyon 1 University, Lyon, France.
⁴ BioFilm Control, Saint-Beauzire, France.
⁵ Orthopedic Surgery Unit, Hospices Civils de Lyon, Lyon, France.
⁶ Laboratory of bacteriology, French National Reference Centre for Staphylococci, Hospices Civils de Lyon, Lyon, France.

Abstract

Introduction: Corynebacteria represent often-neglected etiological agents of post-traumatic and/or post-operative bone and joint infection (BJI). We describe here clinical characteristics and bacteriological determinants of this condition. Methods: A retrospective cohort study described characteristics, outcome and determinants of treatment failure of all patients with proven Corynebacterium spp. BJI (i.e., ≥2 culture-positive gold-standard samples). Available strains were further characterized regarding their antibiotic susceptibilies, abilities to form early (BioFilm Ring Test®) and mature (crystal violet staining method) biofilms and to invade osteoblasts (gentamicin protection assay). Results: The 51 included BJI were mostly chronic (88.2%), orthopedic device-related (74.5%) and polymicrobial (78.4%). After a follow-up of 60.7 weeks (IQR, 30.1-115.1), 20 (39.2%) treatment failures were observed, including 4 Corynebacterium-documented relapses, mostly associated with non-optimal surgical management (OR 7.291; p = 0.039). Internalization rate within MG63 human osteoblasts was higher for strains isolated from delayed (>3 months) BJI (p < 0.001). Infection of murine osteoblasts deleted for the β1-integrin resulted in a drastic reduction in the internalization rate. No difference was observed regarding biofilm formation. Conclusions: Surgical management plays a crucial role in outcome of BJI involving corynebacteria, as often chronic and device-associated infections. Sanctuarisation within osteoblasts, implicating the β1 cellular integrin, may represent a pivotal virulence factor associated with BJI chronicity.

Keywords: Corynebacterium; biofilm; bone and joint infection; intracellular; osteoblasts.