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

Yuka Yamagishi, Hiroshige Mikamo, Hideo Kato, Naoya Nishiyama, Nobuhiro Asai, Yusuke Koizumi, Daisuke Sakanashi, Hiroyuki Suematsu, Katsuhiko Matsuura, Mao Hagihara

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2017 Jun

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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. 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). 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. 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. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Citation

Yuka Yamagishi, Hiroshige Mikamo, Hideo Kato, Naoya Nishiyama, Nobuhiro Asai, Yusuke Koizumi, Daisuke Sakanashi, Hiroyuki Suematsu, Katsuhiko Matsuura, Mao Hagihara. Efficacy of tedizolid against methicillin-resistant Staphylococcus aureus and Peptostreptococcus anaerobius in thigh mixed-infection mouse model. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2017 Jun;23(6):368-373