Pharmacokinetic/pharmacodynamic assessment of the effects of parenteral administration of a fluoroquinolone on the intestinal microbiota: Comparison of bactericidal activity at the gut versus the systemic level in a pig model
Pharmacokinetic/pharmacodynamic assessment of the effects of parenteral administration of a fluoroquinolone on the intestinal microbiota: Comparison of bactericidal activity at the gut versus the systemic level in a pig model
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DOI：
10.1016/j.ijantimicag.2013.07.008
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发表时间：
2013-11-01
影响因子：
10.8
通讯作者：
Bousquet-Melou, Alain
中科院分区：
文献类型：
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作者：
Ferran, Aude A.;Bibbal, Delphine;Bousquet-Melou, Alain
通过结合血浆浓度和最低抑菌浓度 (MIC) 进行的抗菌药物的经典药代动力学/药效学研究通常可以预测药物针对位于与循环血液密切相关的感染部位的目标病原体的活性。然而，这些研究并没有预测肠外抗菌治疗对肠道细菌的影响，肠道细菌可能是物种间或环境中耐药性传播的原因。本研究的目的是评估氟喹诺酮类药物对肺部和肠道细菌的不同抗菌活性。在肌肉注射后评估猪的血浆和肠道浓度，并建立标准肉汤和灭菌肠道内容物中马波沙星浓度与平均细菌接种物生长之间的体外关系模型。结果表明，与猪血浆相比，猪肠道中马波沙星的暴露量增加，但与肉汤相比，消化道内容物中马波沙星对大肠杆菌的活性降低，从而得到补偿。这些结果表明，用于在肺部水平靶向病原体的马波沙星剂量会类似地影响小肠中相同大小且具有相似 MIC 的细菌群。然而，研究表明，与高接种量 (10(8) CFU/mL) 相比，低接种量 (10(5) CFU/mL) 的马波沙星的杀菌活性增加了 4 至 7 倍。这一结果表明，比传统使用的剂量低得多的马波沙星剂量有可能根除低量肺部致病菌，同时对大肠道微生物群的影响最小。 (c) 2013 年 Elsevier B.V. 和国际化疗协会。版权所有。
Classical pharmacokinetic/pharmacodynamic studies of antimicrobial agents performed by combining plasma concentrations and minimum inhibitory concentrations (MICs) are often predictive of the activity of a drug against targeted pathogens located at infectious sites closely connected to circulating blood. However, these studies do not predict the impact of parenteral antimicrobial treatment on intestinal bacteria, which could be responsible for transmission of resistance between species or in the environment. The aim of this study was to assess the differential antibacterial activity of a fluoroquinolone against lung and gut bacteria. Plasma and intestinal concentrations of marbofloxacin were assessed in pigs following intramuscular administration, and the in vitro relationship between marbofloxacin concentrations and mean bacterial inoculum growth in standard broth and in sterilised intestinal contents was modelled. It was shown that the increased intestinal exposure to marbofloxacin compared with plasma in pigs was compensated by reduced marbofloxacin activity against Escherichia coli in the contents of the digestive tract compared with in broth. These results showed that marbofloxacin doses used to target pathogens at the lung level would similarly affect the bacterial population of the same size and with a similar MIC located in the small intestine. However, it was shown that the bactericidal activity of marbofloxacin was increased 4- to 7-fold with low (10(5) CFU/mL) compared with high (10(8) CFU/mL) inoculum sizes. This result suggests that much lower marbofloxacin doses than those classically used would potentially eradicate low pulmonary pathogenic inocula while having a minimal impact on the large gut microbiota. (c) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.