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Differences in Pharmacokinetic/Pharmacodynamic Parameters of Tedizolid Against VRE and MRSA

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Abstract

Purpose

Vancomycin-resistant enterococci (VRE) have recently become a major cause of nosocomial infections and a global public health concern. Tedizolid exhibits powerful antibacterial activity against VRE in vitro, but its pharmacokinetic/pharmacodynamic (PK/PD) parameters remain unclear. Therefore, we aimed to determine the PK/PD indices of tedizolid action on VRE and the mechanisms underlying the PK/PD indices differences of tedizolid against VRE and methicillin-resistant Staphylococcus aureus (MRSA).

Methods

Optimal PK/PD target values of tedizolid were determined in vitro, based on time-kill curves and post-antibiotic effects (PAEs), and in vivo, using mouse models of thigh infection with VRE and MRSA strains.

Results

The tedizolid bactericidal activity on VRE and MRSA was time-dependent. Correlations were closest between fAUC24/MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 log10 kill tedizolid fAUC24/MIC in neutropenic mouse models of thigh infection with VRE and MRSA should be 14.2 and 138.5, respectively. The PAEs of tedizolid against VRE and MRSA were 2.39 and 0.99 h, respectively.

Conclusion

Tedizolid showed bactericidal effects against VRE even in neutropenic mice unlike MRSA, which could be attributed to its longer PAE against VRE. Hence, we hypothesize that tedizolid treatment against VRE infections is promising for achieving therapeutic success in clinical.

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Data Availability

The dataset generated or analyzed during the current study is available from the corresponding author up reasonable request.

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Acknowledgements

We thank Editage (www.editage.com) for the English language editing.

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Authors and Affiliations

  1. Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shiba Koen, Minato-Ku, Tokyo, 105-8512, Japan

    Xiaoxi Liu, Sho Tashiro, Yuki Igarashi, Wataru Takemura, Nana Kojima, Takumi Morita, Marina Hayashi, Yuki Enoki, Kazuaki Taguchi & Kazuaki Matsumoto

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  1. Xiaoxi Liu
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Contributions

Conceptualization: Xiaoxi Liu, Sho Tashiro, Yuki Igarashi, Wataru Takemura, Nana Kojima, Takumi Morita, Marina Hayashi, Yuki Enoki, Kazuaki Taguchi and Kazuaki Matsumoto.

Data curation: Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto.

Formal analysis: Xiaoxi Liu, Yuki Enoki.

Investigation: Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto. Methodology: Xiaoxi Liu, Sho Tashiro, Yuki Igarashi, Wataru Takemura, Nana Kojima, Takumi Morita, and Marina Hayashi.

Project administration: Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, and Kazuaki Matsumoto. Resources: Yuki Enoki, Kazuaki Taguchi, and Kazuaki Matsumoto.

Supervision: Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto.

Validation: Sho Tashiro, Yuki Igarashi, Wataru Takemura, Nana Kojima, Takumi Morita, and Marina Hayashi.

Visualization: Sho Tashiro, Yuki Igarashi, Wataru Takemura, Nana Kojima, Takumi Morita, and Marina Hayashi.

Writing-original draft: Xiaoxi Liu.

Writing-review and editing: Yuki Enoki, Kazuaki Matsumoto.

Corresponding author

Correspondence to Yuki Enoki.

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Liu, X., Tashiro, S., Igarashi, Y. et al. Differences in Pharmacokinetic/Pharmacodynamic Parameters of Tedizolid Against VRE and MRSA. Pharm Res 40, 187–196 (2023). https://doi.org/10.1007/s11095-022-03425-5

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