Efficacy of tedizolid against methicillin-resistant Staphylococcus aureus and Peptostreptococcus anaerobius in thigh mixed-infection mouse model

Abstract

Objective: The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models.

Material and method: Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog₁₀ CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h).

Results: The tedizolid and linezolid MICs for MRSA was 0.25 and 2 μg/ml. Tedizolid MIC for P. anaerobius was 0.12 μg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 μg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, when comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used.

Conclusion: In the neutropenic murine thigh infection model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobius in the treatment of cSSSI.

Keywords: Methicillin-resistant Staphylococcus aureus; Peptostreptococcus anaerobius; Tedizolid; Thigh mixed-infection mouse model.