PDF(Pubmed)
Abstract：
UNASSIGNED: The administration of antibiotics can expose the digestive microbiota of humans and animals to sub-inhibitory concentrations, potentially favouring the selection of resistant bacteria. The minimal selective concentration (MSC) is a key indicator to understand this process. The MSC is defined as the lowest concentration of an antibiotic that promotes the growth of a resistant strain over a susceptible isogenic strain. It represents the lower limit of the sub-minimal inhibitory concentration (MIC) selective window, where resistant mutants can be selected. Previous studies focused on determining the MSC under standard culture conditions, whereas our research aimed to determine the MSC in a model that approximates in vivo conditions.
UNASSIGNED: We investigated the MSC of oxytetracycline (OTC) in Mueller-Hinton broth (MHB) and sterilised intestinal contents (SIC) from the jejunum, caecum and rectum (faeces) of pigs, using two isogenic strains of Escherichia coli (one susceptible and one resistant to OTC). Additionally, the MIC of OTC against the susceptible strain was determined to assess the upper limit of the sub-MIC selective window.
UNASSIGNED: Our study took a novel approach, and the results indicated that MIC and MSC values were lower in MHB than in SIC. In the latter, these values varied depending on the intestinal segment, with distal compartments exhibiting higher MIC and MSC values. Moreover, the sub-MIC selective window of OTC in SIC narrowed from the jejunum to the rectum, with a significantly closer MSC to MIC in faecal SIC.
UNASSIGNED: The results suggest that OTC binds to digestive contents, reducing the fraction of free OTC. However, binding alone does not fully explain our results, and interactions between bacteria and intestinal contents may play a role. Furthermore, our findings provide initial estimates of low concentrations facilitating resistance selection in the gut. Finally, this research enhances the understanding of antimicrobial resistance selection, emphasising the intricate interplay between antibiotics and intestinal content composition in assessing the risk of resistance development in the gut.
UNASSIGNED: We investigated the MSC of oxytetracycline (OTC) in Mueller-Hinton broth (MHB) and sterilised intestinal contents (SIC) from the jejunum, caecum and rectum (faeces) of pigs, using two isogenic strains of Escherichia coli (one susceptible and one resistant to OTC). Additionally, the MIC of OTC against the susceptible strain was determined to assess the upper limit of the sub-MIC selective window.
UNASSIGNED: Our study took a novel approach, and the results indicated that MIC and MSC values were lower in MHB than in SIC. In the latter, these values varied depending on the intestinal segment, with distal compartments exhibiting higher MIC and MSC values. Moreover, the sub-MIC selective window of OTC in SIC narrowed from the jejunum to the rectum, with a significantly closer MSC to MIC in faecal SIC.
UNASSIGNED: The results suggest that OTC binds to digestive contents, reducing the fraction of free OTC. However, binding alone does not fully explain our results, and interactions between bacteria and intestinal contents may play a role. Furthermore, our findings provide initial estimates of low concentrations facilitating resistance selection in the gut. Finally, this research enhances the understanding of antimicrobial resistance selection, emphasising the intricate interplay between antibiotics and intestinal content composition in assessing the risk of resistance development in the gut.
摘要：
■使用抗生素可以使人类和动物的消化微生物群暴露于亚抑制浓度，可能有利于抗性细菌的选择。最小选择性浓度(MSC)是理解该过程的关键指标。MSC定义为促进抗性菌株相对于敏感的等基因菌株生长的抗生素的最低浓度。它表示亚最小抑制浓度（MIC）选择窗口的下限，可以选择抗性突变体。以前的研究集中在标准培养条件下确定MSC，而我们的研究旨在确定接近体内条件的模型中的MSC。
■我们研究了Mueller-Hinton肉汤（MHB）中土霉素（OTC）的MSC和来自空肠的灭菌肠内容物（SIC），猪的盲肠和直肠（粪便），使用两种同基因大肠杆菌菌株（一种对OTC敏感，一种对OTC耐药）。此外,测定OTC对易感菌株的MIC,以评估亚MIC选择窗口的上限.
■我们的研究采用了一种新颖的方法，结果表明，MHB的MIC和MSC值均低于SIC。在后者中,这些值根据肠段的不同而不同，远端区室表现出较高的MIC和MSC值。此外，SIC中OTC的亚MIC选择窗口从空肠到直肠变窄，MSC与粪便SIC中的MIC明显更接近。
■结果表明，OTC与消化内容物结合，降低游离OTC的比例。然而,仅仅结合并不能完全解释我们的结果，细菌和肠道内容物之间的相互作用可能起作用。此外，我们的发现提供了低浓度促进肠道耐药性选择的初步估计.最后,这项研究增强了对抗菌素耐药性选择的理解，在评估肠道耐药性发展的风险时，强调抗生素和肠道内容物组成之间复杂的相互作用。
■我们研究了Mueller-Hinton肉汤（MHB）中土霉素（OTC）的MSC和来自空肠的灭菌肠内容物（SIC），猪的盲肠和直肠（粪便），使用两种同基因大肠杆菌菌株（一种对OTC敏感，一种对OTC耐药）。此外,测定OTC对易感菌株的MIC,以评估亚MIC选择窗口的上限.
■我们的研究采用了一种新颖的方法，结果表明，MHB的MIC和MSC值均低于SIC。在后者中,这些值根据肠段的不同而不同，远端区室表现出较高的MIC和MSC值。此外，SIC中OTC的亚MIC选择窗口从空肠到直肠变窄，MSC与粪便SIC中的MIC明显更接近。
■结果表明，OTC与消化内容物结合，降低游离OTC的比例。然而,仅仅结合并不能完全解释我们的结果，细菌和肠道内容物之间的相互作用可能起作用。此外，我们的发现提供了低浓度促进肠道耐药性选择的初步估计.最后,这项研究增强了对抗菌素耐药性选择的理解，在评估肠道耐药性发展的风险时，强调抗生素和肠道内容物组成之间复杂的相互作用。
