Abstract
BackgroundActinobacillus pleuropneumoniae, formerly known as Haemophilus pleuropneumoniae, can cause pleuropneumoniae in pigs of different ages, leading to significant mortality. Ceftiofur was the first cephalosporin antibiotic used in animals that was effective against gram-negative and gram-positive bacteria. This study aimed to determine the breakpoint of ceftiofur against Actinobacillus pleuropneumoniae based on the investigation of the epidemiologic cutoff value (ECV), and pharmacodynamic-pharmacokinetic breakpoint.ResultsThe epidemiologic cutoff value was 0.125 µg/mL. The results of the pharmacodynamic study showed that the MICs of BW39 were 0.5 µg/mL and 1 µg/mL under in vitro and ex-vivo conditions, respectively, and the minimal bactericidal concentrations (MBCs) under in vitro and ex vivo conditions were both 1 µg/mL. The time-killing profiles of ceftiofur against BW39 were time-dependent. According to the inhibitory sigmoid Emax model, the AUC24 h/MIC values for the bacteriostatic, bactericidal, and elimination effects in serum were 45.73, 63.83, and 69.04 h for healthy pigs, respectively. Based on the Monte Carlo simulation, the COPD was calculated as 2 µg/mL, and the optimized dosage regimen of ceftiofur against Actinobacillus pleuropneumoniae to achieve bacteriostatic, bactericidal, and elimination effects over 24 h was 2.13, 2.97, and 3.42 mg/kg for the 50% target attainment rate (TAR) and 2.47, 3.21, and 3.70 mg/kg for the 90% TAR, respectively.ConclusionsIn this study, the epidemiologic cutoff value was 0.125 µg/mL, as calculated by ECOFFinder software. According to the PK/PD evaluation in vitro and ex vivo, the value of the pharmacodynamics cutoff was 2 µg/mL, as obtained by Monte Carlo simulation. The COPD suggested that the breakpoint could be better than the COWT value because COPD derived from PL/PD data was obtained in vitro and ex vivo, which was more significant. According to the PK/PD parameters, the single bactericidal dose was 3.21 mg/kg for the 90% target, which would be more available to cure Actinobacillus pleuropneumoniae and avoid the emergence of resistance for clinical ceftiofur use.