The pharmacokinetics and pharmacodynamics of cefquinome against Streptococcus agalactiae in a murine mastitis model

PLoS One. 2023 Jan 25;18(1):e0278306. doi: 10.1371/journal.pone.0278306. eCollection 2023.

Abstract

Cefquinome is a new generation cephalosporin that is effective in the treatment of mastitis in animals. In this study, we evaluated the associations between the specific pharmacokinetics and pharmacodynamics (PK/PD) of cefquinome and its antibacterial activity against Streptococcus agalactiae in a mouse model of mastitis. After a single intramammary dose of cefquinome (30, 60, 120, and 240 μg/mammary gland), the concentration of cefquinome in plasma was analysed by liquid chromatography with tandem mass spectrometry (HPLC/MS-MS). The PK parameters were calculated using a one-compartment first-order absorption model. Antibacterial activity was defined as the maximum change in the S. agalactiae population after each dose. An inhibitory sigmoid Emax model was used to evaluate the relationships between the PK/PD index values and antibacterial effects. The duration for which the concentration of the antibiotic (%T) remained above the minimum inhibitory concentration (MIC) was defined as the optimal PK/PD index for assessing antibacterial activity. The values of %T > MIC to reach 0.5-log10CFU/MG, 1-log10 CFU/MG and 2-log10 CFU/MG reductions were 31, 47, and 81%, respectively. When the PK/PD index %T > MIC of cefquinome was >81% in vivo, the density of the Streptococcus agalactiae was reduced by 2-log10. These findings provide a valuable understanding to optimise the dose regimens of cefquinome in the treatment of S. agalactiae infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Female
  • Humans
  • Mastitis* / drug therapy
  • Mastitis* / microbiology
  • Mice
  • Microbial Sensitivity Tests
  • Streptococcus agalactiae*

Substances

  • cefquinome
  • Cephalosporins
  • Anti-Bacterial Agents

Grants and funding

This study was sponsored by Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX1210), the Educational Reform Project of Chongqing Municipal Education Commission (Z213122), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202203511) and .Self prepared project of Animal Husbandry and Veterinary Branch of Heilongjiang Academy of Agricultural Sciences (ZNKT-202207). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.