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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Antimicrobials, Resistance and Chemotherapy

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1533892

Pharmacokinetic and Pharmacodynamic Integration and Resistance Analysis of Cefquinome Against Streptococcus uberis in vitro Dynamic Model

Provisionally accepted
Chongyang  LiChongyang LiJunli  WangJunli WangFanxi  GuoFanxi GuoFengyichi  ZhangFengyichi ZhangBaochang  ChenBaochang ChenZihan  WangZihan WangDi  CaoDi CaoZugong  YuZugong Yu*
  • Nanjing Agricultural University, Nanjing, Jiangsu Province, China

The final, formatted version of the article will be published soon.

Streptococcus uberis (S. uberis) is a major pathogen that causes acute clinical mastitis and its recurrent episodes in dairy cows. In this study, a peristaltic pump one-compartment open model was established to investigate the relationship between the pharmacokinetic and pharmacodynamic (PK/PD) indices of cefquinome (CFQ) against S. uberis. Bactericidal effects of single high-dosage versus multiple low-dosage administrations within the same drug dosage and best-fit dosage were assessed. Static time-killing curves showed that the population of S. uberis was not changed when the drug concentration was below 1 × MIC. The maximum antibacterial effect was observed at 24 h, when the concentration exceeded 2 × MIC, showing a reduction by 5.73 log10 (CFU/mL), and the maximum kill rate was 0.22 h -1 . S. uberis were cleared at 120 h when the concentration was ≥1 mg/L within single high-dosage groups, except for the 0.28 and 0.5 mg/L groups. The multiple-dose groups decreased below 2.22 log10 (CFU/mL) at 48 h and increased to 9 log10 (CFU/mL) at 120 h, but the group of 0.25 mg/L (4, q24) increased at 144 h. As the frequency of administration increased, the lag time increased following a population decline. The correlation coefficients between AUC0-72h/MBC, %T > MBC, and the antibacterial effects were 0.90% and 0.99%, respectively. %T > MBC was the best-fit PK/PD parameter of CFQ against S. uberis. The MIC of S1-S5 strains ranged from 0.0156-0.0625 μg/mL, and biofilm formation ability increased. In conclusion, CFQ showed good efficacy and time-dependence. This study provides a reference for optimizing CFQ administration in S. uberis.

Keywords: pharmacokinetic, Pharmacodynamic, simulation, dynamic model, single highdosage, multiple low-dosage

Received: 06 Dec 2024; Accepted: 11 Jul 2025.

Copyright: © 2025 Li, Wang, Guo, Zhang, Chen, Wang, Cao and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zugong Yu, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China

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