Exploration of Clinical Breakpoint of Danofloxacin for Glaesserella parasuis in Plasma and in PELF

Xu, Zihui; Huang, Anxiong; Luo, Xuan; Zhang, Peng; Huang, Lingli; Wang, Xu; Mi, Kun; Fang, Shiwei; Huang, Xiao; Li, Jun; Zhang, Yuan; Hao, Haihong

doi:10.3390/antibiotics10070808

Cited by 7 publications

(7 citation statements)

References 55 publications

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“…Previous studies showed that there was a gap existing in CO WT and CO CL . It was reported that CO CL of danofloxacin against Glaesserella parasuis was 0.5 µg/mL, but the CO WT of danofloxacin against Glaesserella parasuis was 8 µg/mL [28]. In our result, the CO CL of APR against Salmonella was 8 µg/mL, but the CO WT of APR against Salmonella was 32 µg/mL.…”

Section: Discussionsupporting

confidence: 41%

Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora

Dai

Guo

et al. 2022

IJMS

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The purpose of this study was to establish the clinical breakpoint (CBP) of apramycin (APR) against Salmonella in swine and evaluate its effect on intestinal microbiota. The CBP was established based on three cutoff values of wild-type cutoff value (COWT), pharmacokinetic-pharmadynamic (PK/PD) cutoff value (COPD) and clinical cutoff value (COCL). The effect of the optimized dose regimen based on ex vivo PK/PD study. The evolution of the ileum flora was determined by the 16rRNA gene sequencing and bioinformatics. This study firstly established the COWT, COPD in ileum, and COCL of APR against swine Salmonella, the value of these cutoffs were 32 µg/mL, 32 µg/mL and 8 µg/mL, respectively. According to the guiding principle of the Clinical Laboratory Standards Institute (CLSI), the final CBP in ileum was 32 µg/mL. Our results revealed the main evolution route in the composition of ileum microbiota of diarrheic piglets treated by APR. The change of the abundances of Bacteroidetes and Euryarchaeota was the most obvious during the evolution process. Methanobrevibacter, Prevotella, S24-7 and Ruminococcaceae were obtained as the highest abundance genus. The abundance of Methanobrevibacter increased significantly when APR treatment carried and decreased in cure and withdrawal period groups. The abundance of Prevotella in the tested groups was significantly lower than that in the healthy group. A decreased of abundance in S24-7 was observed after Salmonella infection and increased slightly after cure. Ruminococcaceae increased significantly after Salmonella infection and decreased significantly after APR treatment. In addition, the genera of Methanobrevibacter and Prevotella were defined as the key node. Valine, leucine and isoleucine biosynthesis, D-Glutamine and D-glutamate metabolism, D-Alanine metabolism, Peptidoglycan and amino acids biosynthesis were the top five Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the ileum microbiota of piglets during the Salmonella infection and APR treatment process. Our study extended the understanding of dynamic shift of gut microbes during diarrheic piglets treated by APR.

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Section: Discussionsupporting

confidence: 41%

Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora

Dai

Guo

et al. 2022

IJMS

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“…Similar to other fluoroquinolones, danofloxacin have good penetration into pulmonary epithelial lining fluid (ELF). A previous bronchopulmonary PK study with danofloxacin demonstrated higher peak concentration in ELF compared to plasma in pigs, with a mean ELF/plasma AUC ratio of 5.4 (9). Of note, the pharmacokinetic profiles of danofloxacin were linear and proportional in piglets as described by the result of linear regression analysis (R 2 = 0.951 for AUC 24h ) (36).…”

Section: Discussionmentioning

confidence: 86%

“…Fluoroquinolones, such as danofloxacin, possess excellent PK characteristics that may contribute to clinical success of treating SRD. Such advantages include high peak concentrations in plasma, extensive distribution to most tissues in animal body and deep penetration into lung fluids (8,9). Despite these findings from previous studies, the precise pharmacokinetic/pharmacodynamic (PK/PD) targets and cutoff values of danofloxacin in pigs for SRD pathogens, especially for P. multocida have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Comparison of PK/PD Targets and Cutoff Values for Danofloxacin Against Pasteurella multocida and Haemophilus parasuis in Piglets

et al. 2022

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Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis. Compared to P. multocida, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis. The mean area under the concentration-time curve/MIC (AUC24h/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida, whereas they were 14.6 and 37.8, respectively, for H. parasuis. Danofloxacin AUC24h/MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis. At the current dose of 2.5 mg/kg, the PK/PD cutoff (COPD) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of > 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.

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“…Judging from the results, the results obtained by different algorithms were similar, indicating that different methods have the same goal under the condition of good experimental data. However, under the conditions of different results, the CO CL that meets all the conditions should be selected ( Xu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prudent Use of Tylosin for Treatment of Mycoplasma gallisepticum Based on Its Clinical Breakpoint and Lung Microbiota Shift

et al. 2021

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The aim of this study was to explore the prudent use of tylosin for the treatment of chronic respiratory infectious diseases in chickens caused by Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and its effect on lung microbiota. The CBP was established based on the wild-type/epidemiological cutoff value (COWT/ECV), pharmacokinetics-pharmacodynamics (PK-PD) cutoff value (COPD), and clinical cutoff value (COCL) of tylosin against MG. The minimum inhibitory concentration (MIC) of tylosin against 111 MG isolates was analyzed and the COWT was 2 μg/ml. M17 with MIC of 2 μg/ml was selected as a representative strain for the PK-PD study. The COPD of tylosin against MG was 1 μg/ml. The dosage regimen formulated by the PK-PD study was 3 days administration of tylosin at a dose of 45.88 mg/kg b.w. with a 24-h interval. Five different MIC MGs were selected for clinical trial, and the COCL of tylosin against MG was 0.5 μg/ml. According to the CLSI decision tree, the CBP of tylosin against MG was set up as 2 μg/ml. The effect of tylosin on lung microbiota of MG-infected chickens was analyzed by 16S rRNA gene sequencing. Significant change of the lung microbiota was observed in the infection group and treatment group based on the principal coordinate analysis and the Venn diagrams of the core and unique OTU. The phyla Firmicutes and Proteobacteria showed difference after MG infection and treatment. This study established the CBP of tylosin against MG. It also provided scientific data for the prudent use of tylosin based on the evaluation of MG infection and tylosin treatment on the lung microbiota.

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Exploration of Clinical Breakpoint of Danofloxacin for Glaesserella parasuis in Plasma and in PELF

Cited by 7 publications

References 55 publications

Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora

Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora

Comparison of PK/PD Targets and Cutoff Values for Danofloxacin Against Pasteurella multocida and Haemophilus parasuis in Piglets

Prudent Use of Tylosin for Treatment of Mycoplasma gallisepticum Based on Its Clinical Breakpoint and Lung Microbiota Shift

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