Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF
<b>Background:</b> In order to establish the clinical breakpoint (CBP) of danofloxacin against <i>G. parasuis</i>, three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (CO<sub>PD</sub>) and clinica...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/7/808 |
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| author | Zihui Xu Anxiong Huang Xun Luo Peng Zhang Lingli Huang Xu Wang Kun Mi Shiwei Fang Xiao Huang Jun Li Zonghui Yuan Haihong Hao |
| author_facet | Zihui Xu Anxiong Huang Xun Luo Peng Zhang Lingli Huang Xu Wang Kun Mi Shiwei Fang Xiao Huang Jun Li Zonghui Yuan Haihong Hao |
| author_sort | Zihui Xu |
| collection | DOAJ |
| description | <b>Background:</b> In order to establish the clinical breakpoint (CBP) of danofloxacin against <i>G. parasuis</i>, three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (CO<sub>PD</sub>) and clinical cutoff value (CO<sub>CL</sub>), were obtained in the present study. <b>Methods:</b> The ECV was calculated using ECOFFinder base on the MIC distribution of danfloxacin against 347 <i>G. parasuis</i> collected from disease pigs. The CO<sub>PD</sub> was established based on in vivo and ex vivo PK-PD modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis. The CO<sub>CL</sub> was established based on the relationship between the possibility of cure (POC) and MIC in the clinical trials using the “WindoW” approach, nonlinear regression and CART analysis. <b>Results:</b> The MIC<sub>50</sub> and MIC<sub>90</sub> of danofloxacin against 347 <i>G. parasuis</i> were 2 μg/mL and 8 μg/mL, respectively. The ECV value was set to 8 μg/mL using ECOFFinder. Concentration-time curves of danofloxacin were fitted with a two-compartment PK model. The PK parameters of the maximum concentration (C<sub>max</sub>) and area under concentration-time curves (AUC) in PELF were 3.67 ± 0.25 μg/mL and 24.28 ± 2.70 h·μg/mL, higher than those in plasma (0.67 ± 0.01 μg/mL and 4.47 ± 0.51 h·μg/mL). The peak time (T<sub>max</sub>) in plasma was 0.23 ± 0.07 h, shorter than that in PELF (1.61 ± 0.15 h). The CO<sub>PD</sub> in plasma and PELF were 0.125 μg/mL and 0.5 μg/mL, respectively. The CO<sub>CL</sub> calculated by WindoW approach, nonlinear regression and CART analysis were 0.125–4 μg/mL, 0.428 μg/mL and 0.56 μg/mL, respectively. The 0.5 μg/mL was selected as eligible CO<sub>CL</sub>. The ECV is much higher than the CO<sub>PD</sub> and CO<sub>CL</sub>, and the clinical breakpoint based on data in plasma was largely different from that of PELF. <b>Conclusions:</b> Our study firstly established three cutoff values of danofloxacin against <i>G. parasuis.</i> It suggested that non-wild-type danofloxacin-resistant <i>G. parasuis</i> may lead to ineffective treatment by danofloxacin. |
| first_indexed | 2024-03-10T09:47:42Z |
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| language | English |
| last_indexed | 2024-03-10T09:47:42Z |
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| series | Antibiotics |
| spelling | doaj.art-2b0ae6733ddd4d34aff3a35ece5815a52023-11-22T03:03:30ZengMDPI AGAntibiotics2079-63822021-07-0110780810.3390/antibiotics10070808Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELFZihui Xu0Anxiong Huang1Xun Luo2Peng Zhang3Lingli Huang4Xu Wang5Kun Mi6Shiwei Fang7Xiao Huang8Jun Li9Zonghui Yuan10Haihong Hao11National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China<b>Background:</b> In order to establish the clinical breakpoint (CBP) of danofloxacin against <i>G. parasuis</i>, three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (CO<sub>PD</sub>) and clinical cutoff value (CO<sub>CL</sub>), were obtained in the present study. <b>Methods:</b> The ECV was calculated using ECOFFinder base on the MIC distribution of danfloxacin against 347 <i>G. parasuis</i> collected from disease pigs. The CO<sub>PD</sub> was established based on in vivo and ex vivo PK-PD modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis. The CO<sub>CL</sub> was established based on the relationship between the possibility of cure (POC) and MIC in the clinical trials using the “WindoW” approach, nonlinear regression and CART analysis. <b>Results:</b> The MIC<sub>50</sub> and MIC<sub>90</sub> of danofloxacin against 347 <i>G. parasuis</i> were 2 μg/mL and 8 μg/mL, respectively. The ECV value was set to 8 μg/mL using ECOFFinder. Concentration-time curves of danofloxacin were fitted with a two-compartment PK model. The PK parameters of the maximum concentration (C<sub>max</sub>) and area under concentration-time curves (AUC) in PELF were 3.67 ± 0.25 μg/mL and 24.28 ± 2.70 h·μg/mL, higher than those in plasma (0.67 ± 0.01 μg/mL and 4.47 ± 0.51 h·μg/mL). The peak time (T<sub>max</sub>) in plasma was 0.23 ± 0.07 h, shorter than that in PELF (1.61 ± 0.15 h). The CO<sub>PD</sub> in plasma and PELF were 0.125 μg/mL and 0.5 μg/mL, respectively. The CO<sub>CL</sub> calculated by WindoW approach, nonlinear regression and CART analysis were 0.125–4 μg/mL, 0.428 μg/mL and 0.56 μg/mL, respectively. The 0.5 μg/mL was selected as eligible CO<sub>CL</sub>. The ECV is much higher than the CO<sub>PD</sub> and CO<sub>CL</sub>, and the clinical breakpoint based on data in plasma was largely different from that of PELF. <b>Conclusions:</b> Our study firstly established three cutoff values of danofloxacin against <i>G. parasuis.</i> It suggested that non-wild-type danofloxacin-resistant <i>G. parasuis</i> may lead to ineffective treatment by danofloxacin.https://www.mdpi.com/2079-6382/10/7/808danofloxacin<i>Glaesserella parasuis</i>epidemiological cutoff valuesPK-PD cutoff valuesclinical cutoff valuesclinical breakpoint |
| spellingShingle | Zihui Xu Anxiong Huang Xun Luo Peng Zhang Lingli Huang Xu Wang Kun Mi Shiwei Fang Xiao Huang Jun Li Zonghui Yuan Haihong Hao Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF Antibiotics danofloxacin <i>Glaesserella parasuis</i> epidemiological cutoff values PK-PD cutoff values clinical cutoff values clinical breakpoint |
| title | Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF |
| title_full | Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF |
| title_fullStr | Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF |
| title_full_unstemmed | Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF |
| title_short | Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF |
| title_sort | exploration of clinical breakpoint of danofloxacin for i glaesserella parasuis i in plasma and in pelf |
| topic | danofloxacin <i>Glaesserella parasuis</i> epidemiological cutoff values PK-PD cutoff values clinical cutoff values clinical breakpoint |
| url | https://www.mdpi.com/2079-6382/10/7/808 |
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