Osteoarticular infections involving linezolid-resistant Staphylococcus epidermidis: a retrospective multicenter study in French Reference Centers

Objectives: The choice of the best probabilistic postoperative antibiotics in bone and joint infections (BJI) is challenging. Since the implementation of protocolized postoperative Linezolid in 6 French referral centers, strains of linezolid-resistant Staphylococcus epidermidis (LR-MDRSE) were isolated in patients with BJI. We aimed here to describe clinical, microbiological and molecular patterns associated with these strains. Methods: All patients with at least one intraoperative specimen of LR-MDRSE between 2015 and 2020, were included in this retrospective multicentric study. Clinical presentation, management and outcome were described. Investigation of LR-MDRSE strains included definition of MICs to linezolid and most recent anti-MRSA drugs, genetic determinants of resistance and phylogenetic analysis. Results: 46 patients were included in 5 centers, 45 had prior exposure to linezolid, 33 had foreign devices. 10 patients had colonization and 36 infection. Clinical success was achieved for 26 patients. Incidence of LR-MDRSE increased over the study period. All strains were highly resistant to oxazolidinones, and resistant to gentamicin, clindamycin, ofloxacin, rifampicin, ceftaroline and ceftobiprole, but were susceptible to cyclins, daptomycin, and dalbavancin. Susceptibility to delafloxacin was bimodal. Molecular analysis was done for 44 strains, the main mutation conferring resistance to oxazolidinones was the G2576T. All strains belonged to the ST-2 clonal complex, and phylogenetic analysis showed emergence of 5 clades corresponding geographically to centers. Conclusions: We showed the emergence of new clonal populations of highly resistant S. epidermidis in BJI. Identifying at risk patients of LR-MDRSE acquisition and propose alternatives to systematic post-operative linezolid use becomes essential.