Abstract
We wished to study the detailed and precise antibacterial activity of cefquinome against Actinobacillus pleuropneumoniae (APP) in vitro and ex vivo. We analyzed the relationships between kill rate and cefquinome concentration in broth and between pharmacokinetic/pharmacodynamic (PK/PD) parameters and antibacterial effect in serum and tissue cage fluid (TCF) of piglets. Cefquinome exhibited time-dependent antibacterial activity against APP according to the kill rate. The maximum kill rate was 0.48 log10 CFU/mL/h at the 0-9-h period in broth. In the ex vivo PK/PD study, the maximum concentration (Cmax), time to reach the maximum concentration (Tmax), terminal half-life (T1/2β), and area under the concentration time curve (AUCinfinity) were 5.65 μg/ml, 0.58 h, 2.24 h, and 18.48 μg·h/ml in serum and 1.13 μg/ml, 2.60 h, 12.22 h, and 20.83 μg·h/ml in TCF, respectively. The values of area under the curve during 24 h/minimum inhibitory concentration (AUC24h/MIC) for bacteriostatic, bactericidal, and bacterial eradication effects were 18.94, 246.8, and 1013.23 h in serum and 4.20, 65.81, and 391.35 h in TCF, respectively. Our findings will provide a valuable basis for optimization of dosage regimens when applying cefquinome to treat APP infection.
Highlights
Porcine contagious pleuropneumonia (PCP), caused by Actinobacillus pleuropneumoniae (APP), is a serious respiratory system diseases in pigs [1, 2]
The maximum kill rate during each period; EC50, the cefquinome concentration producing 50% of the maximum kill rate; E0, the kill rate in control tryptic soy broth (TSB); N, the Hill coefficient that describes the steepness of the curve for the kill rate and cefquinome concentration; R2, the correlation coefficient between the kill rate and cefquinome concentration
We found that the antibacterial activity of cefquinome against APP was according to time-dependent drug characteristics
Summary
Porcine contagious pleuropneumonia (PCP), caused by Actinobacillus pleuropneumoniae (APP), is a serious respiratory system diseases in pigs [1, 2]. The classical symptoms of acute PCP are hemorrhagic necrotizing pneumonia and fibrinous pneumonia with high morbidity and mortality [3, 4]. PCP has caused considerable economic losses to farmers and severely restricted the development of the pig industry. Because the serotype of A. pleuropneumoniae was more than those of 19 species and there was no effectively and commonly used vaccine to protect pigs at present [5,6,7]. Antimicrobial therapy is still a rapid and efficacious method for PCP treatment, such as cephalosporins, fluoroquinolones, and macrolides [8,9,10,11,12,13,14]
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