An in vitro evaluation of the efficacy of tedizolid: implications for the treatment of skin and soft tissue infections

Abstract

Skin and soft tissue infections (SSTI) are among the most commonly occurring infections and evidence suggests that these are increasing world-wide. The aetiology is diverse, but Staphylococcus aureus predominate and these are often resistant to antimicrobials that were previously effective. Tedizolid is a new oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI caused by Gram-positive pathogens, including S. aureus. The aim of this study was to evaluate the in vitro efficacy of tedizolid in comparison to other clinically used antibacterials against antibiotic sensitive- and resistant-staphylococci, grown in planktonic cultures and as biofilms reflecting the growth of the microorganism during episodes of SSTI. Against a panel of 66 clinical staphylococci, sensitivity testing revealed that a lower concentration of tedizolid was required to inhibit the growth of staphylococci compared to linezolid, vancomycin and daptomycin; with the tedizolid MIC₅₀ being 8-fold (S. aureus) or 4-fold (S. epidermidis) below that obtained for linezolid. In addition, cfr+ linezolid-resistant strains remained fully susceptible to tedizolid. Against S. aureus biofilms, 10×MIC tedizolid was superior or comparable with 10×MIC comparator agents in activity, and superior to 10×MIC linezolid against those formed by S. epidermidis (65 vs. 33% reduction, respectively). Under flow-conditions both oxazolidinones at 10×MIC statistically out-performed vancomycin in their ability to reduce the viable cell count within a S. aureus biofilm with fewer the 12% of cells surviving compared to 63% of cells. In conclusion, tedizolid offers a realistic lower-dose alternative agent to treat staphylococcal SSTI, including infections caused by multi-drug resistant strains.

Keywords: biofilm; linezolid; minimum inhibitory concentration; skin and soft tissue infections; staphylococcus; tedizolid.