Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study
Clostridium perfringens causes significant morbidity and mortality in swine worldwide. Avilamycin showed no cross resistance and good activity for treatment of C. perfringens. The aim of this study was to formulate optimal regimens of avilamycin treatment for C. perfringens infection based on the cl...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.769539/full |
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| author | Anxiong Huang Anxiong Huang Xun Luo Xun Luo Zihui Xu Zihui Xu Lingli Huang Lingli Huang Xu Wang Xu Wang Shuyu Xie Shuyu Xie Yuanhu Pan Yuanhu Pan Shiwei Fang Shiwei Fang Zhenli Liu Zhenli Liu Zonghui Yuan Zonghui Yuan Haihong Hao Haihong Hao |
| author_facet | Anxiong Huang Anxiong Huang Xun Luo Xun Luo Zihui Xu Zihui Xu Lingli Huang Lingli Huang Xu Wang Xu Wang Shuyu Xie Shuyu Xie Yuanhu Pan Yuanhu Pan Shiwei Fang Shiwei Fang Zhenli Liu Zhenli Liu Zonghui Yuan Zonghui Yuan Haihong Hao Haihong Hao |
| author_sort | Anxiong Huang |
| collection | DOAJ |
| description | Clostridium perfringens causes significant morbidity and mortality in swine worldwide. Avilamycin showed no cross resistance and good activity for treatment of C. perfringens. The aim of this study was to formulate optimal regimens of avilamycin treatment for C. perfringens infection based on the clinical breakpoint (CBP). The wild-type cutoff value (COWT) was defined as 0.25 μg/ml, which was developed based on the minimum inhibitory concentration (MIC) distributions of 120 C. perfringens isolates and calculated using ECOFFinder. Pharmacokinetics–pharmacodynamics (PK-PD) of avilamycin in ileal content were analyzed based on the high-performance liquid chromatography method and WinNonlin software to set up the target of PK/PD index (AUC0–24h/MIC)ex based on sigmoid Emax modeling. The PK parameters of AUC0–24h, Cmax, and Tmax in the intestinal tract were 428.62 ± 14.23 h μg/mL, 146.30 ± 13.41 μg/ml,, and 4 h, respectively. The target of (AUC0–24h/MIC)ex for bactericidal activity in intestinal content was 36.15 h. The PK-PD cutoff value (COPD) was defined as 8 μg/ml and calculated by Monte Carlo simulation. The dose regimen designed from the PK-PD study was 5.2 mg/kg mixed feeding and administrated for the treatment of C. perfringens infection. Five respective strains with different MICs were selected as the infection pathogens, and the clinical cutoff value was defined as 0.125 μg/ml based on the relationship between MIC and the possibility of cure (POC) following nonlinear regression analysis, CART, and “Window” approach. The CBP was set to be 0.25 μg/ml and selected by the integrated decision tree recommended by the Clinical Laboratory of Standard Institute. The formulation of the optimal regimens and CBP is good for clinical treatment and to control drug resistance. |
| first_indexed | 2024-12-13T13:39:27Z |
| format | Article |
| id | doaj.art-65fcd66279fa4dcdbd22896698465adf |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T13:39:27Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-65fcd66279fa4dcdbd22896698465adf2022-12-21T23:43:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.769539769539Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD StudyAnxiong Huang0Anxiong Huang1Xun Luo2Xun Luo3Zihui Xu4Zihui Xu5Lingli Huang6Lingli Huang7Xu Wang8Xu Wang9Shuyu Xie10Shuyu Xie11Yuanhu Pan12Yuanhu Pan13Shiwei Fang14Shiwei Fang15Zhenli Liu16Zhenli Liu17Zonghui Yuan18Zonghui Yuan19Haihong Hao20Haihong Hao21National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA (Ministry of Agriculture) Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, ChinaMOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, ChinaClostridium perfringens causes significant morbidity and mortality in swine worldwide. Avilamycin showed no cross resistance and good activity for treatment of C. perfringens. The aim of this study was to formulate optimal regimens of avilamycin treatment for C. perfringens infection based on the clinical breakpoint (CBP). The wild-type cutoff value (COWT) was defined as 0.25 μg/ml, which was developed based on the minimum inhibitory concentration (MIC) distributions of 120 C. perfringens isolates and calculated using ECOFFinder. Pharmacokinetics–pharmacodynamics (PK-PD) of avilamycin in ileal content were analyzed based on the high-performance liquid chromatography method and WinNonlin software to set up the target of PK/PD index (AUC0–24h/MIC)ex based on sigmoid Emax modeling. The PK parameters of AUC0–24h, Cmax, and Tmax in the intestinal tract were 428.62 ± 14.23 h μg/mL, 146.30 ± 13.41 μg/ml,, and 4 h, respectively. The target of (AUC0–24h/MIC)ex for bactericidal activity in intestinal content was 36.15 h. The PK-PD cutoff value (COPD) was defined as 8 μg/ml and calculated by Monte Carlo simulation. The dose regimen designed from the PK-PD study was 5.2 mg/kg mixed feeding and administrated for the treatment of C. perfringens infection. Five respective strains with different MICs were selected as the infection pathogens, and the clinical cutoff value was defined as 0.125 μg/ml based on the relationship between MIC and the possibility of cure (POC) following nonlinear regression analysis, CART, and “Window” approach. The CBP was set to be 0.25 μg/ml and selected by the integrated decision tree recommended by the Clinical Laboratory of Standard Institute. The formulation of the optimal regimens and CBP is good for clinical treatment and to control drug resistance.https://www.frontiersin.org/articles/10.3389/fphar.2022.769539/fullClostridium perfringensavilamycinoptimal regimensclinical breakpointPK-PD |
| spellingShingle | Anxiong Huang Anxiong Huang Xun Luo Xun Luo Zihui Xu Zihui Xu Lingli Huang Lingli Huang Xu Wang Xu Wang Shuyu Xie Shuyu Xie Yuanhu Pan Yuanhu Pan Shiwei Fang Shiwei Fang Zhenli Liu Zhenli Liu Zonghui Yuan Zonghui Yuan Haihong Hao Haihong Hao Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study Frontiers in Pharmacology Clostridium perfringens avilamycin optimal regimens clinical breakpoint PK-PD |
| title | Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study |
| title_full | Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study |
| title_fullStr | Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study |
| title_full_unstemmed | Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study |
| title_short | Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study |
| title_sort | optimal regimens and clinical breakpoint of avilamycin against clostridium perfringens in swine based on pk pd study |
| topic | Clostridium perfringens avilamycin optimal regimens clinical breakpoint PK-PD |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.769539/full |
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