Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model
IntroductionStreptococcus uberis (S. uberis) is a major pathogen that causes acute clinical mastitis and its recurrent episodes in dairy cows.MethodsIn this study, a peristaltic pump one-compartment open model was established to investigate the relationship between the pharmacokinetic and pharmacody...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1533892/full |
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| author | Chongyang Li Junli Wang Fanxi Guo Fengyichi Zhang Baochang Chen Zihan Wang Di Cao Zugong Yu |
| author_facet | Chongyang Li Junli Wang Fanxi Guo Fengyichi Zhang Baochang Chen Zihan Wang Di Cao Zugong Yu |
| author_sort | Chongyang Li |
| collection | DOAJ |
| description | IntroductionStreptococcus uberis (S. uberis) is a major pathogen that causes acute clinical mastitis and its recurrent episodes in dairy cows.MethodsIn 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.ResultsStatic 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.DiscussionIn conclusion, CFQ showed good efficacy and time-dependence. This study provides a reference for optimizing CFQ administration in S. uberis. |
| format | Article |
| id | doaj-art-02efd5887a2b439ebf9cf643d2eab6f3 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-02efd5887a2b439ebf9cf643d2eab6f32025-08-20T03:51:49ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.15338921533892Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic modelChongyang LiJunli WangFanxi GuoFengyichi ZhangBaochang ChenZihan WangDi CaoZugong YuIntroductionStreptococcus uberis (S. uberis) is a major pathogen that causes acute clinical mastitis and its recurrent episodes in dairy cows.MethodsIn 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.ResultsStatic 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.DiscussionIn conclusion, CFQ showed good efficacy and time-dependence. This study provides a reference for optimizing CFQ administration in S. uberis.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1533892/fullpharmacokineticpharmacodynamicsimulationdynamic modelsingle high dosagemultiple low-dosage |
| spellingShingle | Chongyang Li Junli Wang Fanxi Guo Fengyichi Zhang Baochang Chen Zihan Wang Di Cao Zugong Yu Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model Frontiers in Microbiology pharmacokinetic pharmacodynamic simulation dynamic model single high dosage multiple low-dosage |
| title | Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model |
| title_full | Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model |
| title_fullStr | Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model |
| title_full_unstemmed | Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model |
| title_short | Pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against Streptococcus uberis in vitro dynamic model |
| title_sort | pharmacokinetic and pharmacodynamic integration and resistance analysis of cefquinome against streptococcus uberis in vitro dynamic model |
| topic | pharmacokinetic pharmacodynamic simulation dynamic model single high dosage multiple low-dosage |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1533892/full |
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