De Smet Joren, Boyen Filip, Croubels Siska, Rasschaert Geertrui, Haesebrouck Freddy, De Backer Patrick, Devreese Mathias
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Front Pharmacol. 2018 Nov 6;9:1265. doi: 10.3389/fphar.2018.01265. eCollection 2018.
Florfenicol, which is licensed for veterinary use only, proves to be a potent antimicrobial for treatment of respiratory disease. However, the subsequent exposure of the gut microbiota to florfenicol is not well described. Hence, the effect of various administration protocols on both plasma and gastro-intestinal florfenicol concentrations in pigs was evaluated. In field situations were simulated by application of different administration routes and dosages [single oral bolus at 10 or 5 mg/kg body weight (BW), medicated feed at 10 or 5 mg/kg BW and intramuscular injections at 15 or 30 mg/kg BW]. After intramuscular administration of 30 mg florfenicol/kg BW, gastro-intestinal concentrations of florfenicol, quantified 10 h after the last administration, were significantly elevated in comparison with the other treatment groups and ranging between 31.5 and 285.8 μg/g over the different gut segments. For the other treatment groups, the influence of dose and administration route was not significantly different. Bacteriological analysis of the fecal samples from the animals at the start of the experiment, demonstrated the presence of both florfenicol susceptible (with minimal inhibitory concentration (MIC) values of 2-16 μg/mL) and florfenicol resistant (MIC ≥ 256 μg/mL) isolates in all treatment groups. Following, at 10 h after the last administration the susceptible population was eradicated in all treatment groups due to the high intestinal florfenicol concentrations measured. Moreover, selection of the resistant strains during treatment occurred in all groups. This is likely related to the fact that the different treatment strategies led to high gastro-intestinal concentrations albeit not reaching the high magnitude of MIC values associated with florfenicol resistance (≥256 μg/mL). Conclusively, in our experimental setup the administration route and dose alterations studied, had no influence on monitored florfenicol resistance selection in from the microbiota.
氟苯尼考仅被许可用于兽医领域，它被证明是治疗呼吸道疾病的一种强效抗菌药物。然而，肠道微生物群随后接触氟苯尼考的情况尚未得到充分描述。因此，评估了不同给药方案对猪血浆和胃肠道中氟苯尼考浓度的影响。通过应用不同的给药途径和剂量（10或5毫克/千克体重的单次口服大剂量给药、10或5毫克/千克体重的加药饲料给药以及15或30毫克/千克体重的肌肉注射）来模拟实际情况。在肌肉注射30毫克氟苯尼考/千克体重后，在最后一次给药10小时后定量的胃肠道中氟苯尼考浓度，与其他治疗组相比显著升高，并且在不同肠道段中浓度范围为31.5至285.8微克/克。对于其他治疗组，剂量和给药途径的影响没有显著差异。在实验开始时对动物粪便样本进行的细菌学分析表明，所有治疗组中都存在对氟苯尼考敏感（最低抑菌浓度（MIC）值为2 - 16微克/毫升）和对氟苯尼考耐药（MIC≥256微克/毫升）的分离株。随后，在最后一次给药10小时后，由于测得的肠道氟苯尼考浓度较高，所有治疗组中的敏感菌群体均被根除。此外，在所有组中治疗期间都出现了耐药菌株的选择。这可能与以下事实有关，即不同的治疗策略导致胃肠道浓度较高，尽管未达到与氟苯尼考耐药性相关的高MIC值（≥256微克/毫升）。总之，在我们的实验设置中，所研究的给药途径和剂量变化对微生物群中监测到的氟苯尼考耐药性选择没有影响。
