AUTHOR=Zhou Yu-Feng , Sun Zhen , Wang Rui-Ling , Li Jian-Guo , Niu Chao-Yan , Li Xian-An , Feng Yun-Yun , Sun Jian , Liu Ya-Hong , Liao Xiao-Ping 

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

JOURNAL=Frontiers in Veterinary Science

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2022.811967

DOI=10.3389/fvets.2022.811967

ISSN=2297-1769

ABSTRACT=<p>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 <italic>P. multocida</italic> and <italic>H. parasuis</italic> 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 <italic>P. multocida</italic> isolates and 263 <italic>H. parasuis</italic> 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 <italic>H. parasuis</italic>. Compared to <italic>P. multocida</italic>, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against <italic>H. parasuis</italic>. The mean area under the concentration-time curve/MIC (AUC<sub>24h</sub>/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for <italic>P. multocida</italic>, whereas they were 14.6 and 37.8, respectively, for <italic>H. parasuis</italic>. Danofloxacin AUC<sub>24h</sub>/MIC targets for the same endpoints for <italic>P. multocida</italic> were higher than those for <italic>H. parasuis</italic>. At the current dose of 2.5 mg/kg, the PK/PD cutoff (CO<sub>PD</sub>) values of danofloxacin against <italic>P. multocida</italic> and <italic>H. parasuis</italic> 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 &gt; 90% to cover the overall MIC population distributions of <italic>P. multocida</italic> and <italic>H. parasuis</italic> 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.</p>