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Background <p>Orbifloxacin is a broad-spectrum fluoroquinolone antibiotic developed for veterinary use in the treatment of skin and soft tissue infections, as well as respiratory tract infections. This study aimed to define the pharmacokinetic/pharmacodynamic (PK/PD) indices and target exposures associated with antibacterial activity, thereby providing a rational framework for the development and optimization of orbifloxacin dosing regimens in the treatment of <i>Staphylococcus aureus</i> infections.</p> Results <p>The PK profiles and PK/PD relationship of orbifloxacin against <i>S. aureus</i> were investigated using a neutropenic murine thigh infection model with multiple dosing regimens. Orbifloxacin exhibited a short-duration post-antibiotic effect (PAE; 0.12–2.45&#xa0;h) and a longer post-antibiotic sub-MIC effect (PA-SME; 2.13–5.29&#xa0;h) against <i>S. aureus</i>. The dose-response analysis indicated that the area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio over 24&#xa0;h (AUC<sub>24h</sub>/MIC) was a strong PK/PD index predictive of antibacterial efficacy (R² &gt;0.98). AUC<sub>24h</sub>/MIC targets of 33.78–37.79&#xa0;h, 53.30–61.56&#xa0;h, 88.59–98.35&#xa0;h, and 179.43–217.47&#xa0;h were required to achieve bacteriostatic, 1-log<sub>10</sub>, 2-log<sub>10</sub>, and 3-log<sub>10</sub> bacterial reductions, respectively.</p> Conclusions <p>The results confirm that AUC<sub>24h</sub>/MIC is an appropriate PK/PD index for predicting antibacterial efficacy and establish target exposure values required to achieve various levels of bacterial kill.</p>

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In vivo pharmacokinetic and pharmacodynamic profiles of orbifloxacin against Staphylococcus aureus in a neutropenic murine thigh infection model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月29日

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  • Long-Gen Zhong,
  • Si-Jia Tang,
  • Liu-Yan Liang,
  • Xin Yao,
  • Li-Wen Sun,
  • Jian Sun,
  • Xiao-Ping Liao,
  • Yu-Feng Zhou

摘要

Background

Orbifloxacin is a broad-spectrum fluoroquinolone antibiotic developed for veterinary use in the treatment of skin and soft tissue infections, as well as respiratory tract infections. This study aimed to define the pharmacokinetic/pharmacodynamic (PK/PD) indices and target exposures associated with antibacterial activity, thereby providing a rational framework for the development and optimization of orbifloxacin dosing regimens in the treatment of Staphylococcus aureus infections.

Results

The PK profiles and PK/PD relationship of orbifloxacin against S. aureus were investigated using a neutropenic murine thigh infection model with multiple dosing regimens. Orbifloxacin exhibited a short-duration post-antibiotic effect (PAE; 0.12–2.45 h) and a longer post-antibiotic sub-MIC effect (PA-SME; 2.13–5.29 h) against S. aureus. The dose-response analysis indicated that the area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio over 24 h (AUC24h/MIC) was a strong PK/PD index predictive of antibacterial efficacy (R² >0.98). AUC24h/MIC targets of 33.78–37.79 h, 53.30–61.56 h, 88.59–98.35 h, and 179.43–217.47 h were required to achieve bacteriostatic, 1-log10, 2-log10, and 3-log10 bacterial reductions, respectively.

Conclusions

The results confirm that AUC24h/MIC is an appropriate PK/PD index for predicting antibacterial efficacy and establish target exposure values required to achieve various levels of bacterial kill.