# Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model

## TL;DR

This study examines how cefquinome affects Streptococcus uberis in a lab model to determine optimal dosing strategies for treating mastitis in dairy cows.

## Contribution

The study introduces a dynamic in vitro model to analyze cefquinome's pharmacokinetic/pharmacodynamic effects and resistance patterns against S. uberis.

## Key findings

- Cefquinome's maximum antibacterial effect occurs when concentration exceeds 2× MIC, reducing S. uberis by 5.73 log10 (CFU/mL).
- Multiple low-dose administrations led to bacterial regrowth at 120 hours, unlike single high-dose groups.
- %T > MBC was identified as the best PK/PD parameter for cefquinome against S. uberis.

## Abstract

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.