Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose.
- 作者列表："Nikolaou E","Kamilari E","Savkov D","Sergeev A","Zakharova I","Vogazianos P","Tomazou M","Antoniades A","Shammas C
BACKGROUND:Next-generation sequencing has revolutionized our perspective on the gut microbiome composition, revealing the true extent of the adverse effects of antibiotics. The impact of antibiotic treatment on gut microbiota must be considered and researched to provide grounds for establishing new treatment strategies that are less devastating on commensal bacteria. This study investigates the impact on gut microbiome when a commonly used antibiotic, azithromycin is administered, as well as uncovers the benefits induced when it is used in combination with lactulose, a prebiotic known to enhance the proliferation of commensal microbes. METHODS:16S rRNA gene sequencing analysis of stool samples obtained from 87 children treated with azithromycin in combination with or without lactulose have been determined. Children's gut microbial profile was established at the pre- and post-treatment stage. RESULTS:Azithromycin caused an increase in the relative abundance of opportunistic pathogens such as Streptococcus that was evident 60 days after treatment. While few days after treatment, children who also received lactulose started to show a higher relative abundance of saccharolytic bacteria such as Lactobacillus, Enterococcus, Anaerostipes, Blautia and Roseburia, providing a protective role against opportunistic pathogens. In addition, azithromycin-prebiotic combination was able to provide a phylogenetic profile more similar to the pre-treatment stage. CONCLUSION:It is suggested that during azithromycin treatment, lactulose is able to reinstate the microbiome equilibrium much faster as it promotes saccharolytic microbes and provides a homeostatic effect that minimizes the opportunistic pathogen colonization.
背景: 新一代测序彻底改变了我们对肠道微生物组组成的观点，揭示了抗生素不良反应的真实程度。必须考虑和研究抗生素治疗对肠道菌群的影响，为建立对共生菌破坏性较小的新治疗策略提供依据。这项研究调查了当使用一种常用抗生素阿奇霉素时对肠道菌群的影响，以及揭示了当它与乳果糖联合使用时所带来的益处,一种已知可增强共生微生物增殖的益生元。 方法: 对 87 例接受阿奇霉素联合或不联合乳果糖治疗的儿童粪便样本进行 16S rRNA 基因测序分析。在治疗前和治疗后阶段建立了儿童肠道微生物谱。 结果: 阿奇霉素可引起链球菌等条件致病菌的相对丰度增加，治疗后 60 d 明显。虽然在治疗后几天，也接受乳果糖的儿童开始表现出更高的相对丰度的糖分解细菌，如乳酸杆菌，肠球菌，厌氧菌，布洛蒂亚和罗斯布里亚,提供对条件致病菌的保护作用。此外，阿奇霉素-益生元组合能够提供与治疗前阶段更相似的系统发育特征。 结论: 提示在阿奇霉素治疗期间，乳果糖能够更快地恢复微生物组平衡，因为它促进糖化微生物，并提供稳态作用，使条件致病菌定植最小化。
METHODS:OBJECTIVES:To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN:A multicenter randomized sham-controlled clinical trial. SETTING:Twelve ICUs in Canada. PATIENTS:We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS:Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS:The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS:Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
METHODS:RATIONALE:The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared to a lesser amount of calories are unknown. OBJECTIVES:Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality of life scores, return to work and key life activities and reduce death and disability six months later. METHODS:We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition. MEASUREMENTS AND MAIN RESULTS:Participants assigned energy-dense nutrition received more calories (% recommended energy intake, mean (SD) (energy-dense: 103% (28) vs. usual: 69% (18)). Mortality at day-180 was similar (560/1895 (29.6%) vs. 539/1920 (28.1%); relative risk 1.05 (95%CI, 0.95 to 1.16)). At a median [IQR] of 185 [182, 193] days after randomization, 2492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality of life questionnaire visual analogue scale, median [IQR]: 75 [60-85]; group difference: 0 (95%CI, 0 to 0)). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n=818). There was no observed difference in disability (n=1208) or participation in key life activities (n=705). CONCLUSIONS:The delivery of approximately 100% compared to 70% of recommended calorie intake during critical illness does not improve quality of life, or functional outcomes, or increase the number of survivors six months later. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02306746.
METHODS:BACKGROUND:Provision of enteral nutrition with jejunal feeding in upper gastrointestinal obstruction is highly recommended. Access to jejunum can be obtained surgically, percutaneously, or endoscopically. Our institution routinely and preferentially utilizes a silicone nasojejunal tube that is inserted past the obstruction endoscopically. We use a custom dual channel tube that allows feeding at the distal tip and another channel 40 cm from the tip that enables decompression proximally. This is a report of our experience with this custom nasojejunal tube. METHODS:This is a prospective observational study of 201 patients who underwent endoscopic nasojejunal wire-guided feeding tube insertions for obstruction of either the esophagus or the stomach including both benign and malignant pathologies between January 2015 to June 2018 in Hospital Sungai Buloh and Hospital Sultanah Aminah, Malaysia. The indications for tube insertion, insertion technique, and tube-related problems were described. RESULTS:The nasojejunal tube was used to establish enteral feeding in patients with obstructing tumors of the distal esophagus in 65 patients (32.3%) and gastric outlet obstruction in 72 patients (35.8%). There were 54 patients (26.9%) who required reinsertion. The most common reason for reinsertion was unintentional dislodgement, where 32 patients (15.9%) followed by tube blockage 20 patients (10.0%). Using our method of advancement under direct vision, we had only 2 cases of malposition due to severely deformed anatomy. We had no incidence of aspiration in this group of patients and overall, the patients tolerated the tube well. CONCLUSIONS:The novel nasojejunal feeding tube with gastric decompression function is a safe and effective method of delivery of enteral nutrition in patients with upper gastrointestinal obstruction. These tubes if inserted properly are well tolerated with almost no risk of malposition and are tolerated well even for prolonged periods of time until definitive surgery could be performed.