Methods: The current study evaluates the effects of subinhibitory concentrations of tedizolid on transcription and translation of staphylococcal exotoxins in both methicillin-resistant and methicillin-sensitive S. aureus. At 0, 3, 6, 9, 12, and 24 hours following treatment with subinhibitory concentrations of tedizolid, toxin transcript expression and protein production were quantified using real-time PCR and toxin-specific assays, respectively, and compared to samples treated with linezolid or nafcillin.
Results: Subinhibitory levels of tedizolid and linezolid effectively reduce the expression of Alpha-hemolysin, PVL and TSST-1 toxin during S. aureus growth. In contrast, subinhibitory concentrations of nafcillin only reduce toxin production when bacterial growth is severely impaired. The subinhibitory level of tedizolid, or linezolid, required to inhibit toxin production is strain-dependent and coincides with the quantity of toxin produced.
Conclusion: Tedizolid and linezolid are comparable in their ability to inhibit toxin production at similar MIC doses; however, tedizolid inhibits S. aureus growth at a concentration 4- to 8-fold lower than linezolid allowing tedizolid to more potently inhibit toxin production at a lower overall drug concentration.
Merck & Co.:
A. Bryant, Merck & Co.: Grant Investigator , Research grant
D. Stevens, None