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临床试验/NCT05169255
NCT05169255已完成3 期

Long Term Antibiotics Study

University of California, San Diego0 个研究点目标入组 60 人开始时间: 2012年12月7日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
入组人数
60
主要终点
Microbiome

研究概览

简要总结

Antibiotics are a mainstay of life-saving interventions used frequently in medical practice to combat infections. These medications not only target the pathogenic bacteria for which they are prescribed but also function against commensal bacterial communities that inhabit the gut, skin, and oropharynx. The role that these native bacterial communities play in normal host function, such as in nutrition and host immunity, is only beginning to be explored, as are the changes in the communities and their function as a result of various alterations of antibiotic use. Short courses of antibiotics have been shown to affect the diversity of native bacterial communities, and to affect the abundance of antibiotic resistance genes present. For example, use of clindamycin in human subjects for 7 days has been demonstrated to result in persistent clindamycin resistance for months or years. The impact of prolonged antibiotic therapy on the host microbiome including both those organisms present and the diversity of antibiotic genes has not been studied, and we have very little understanding of the longitudinal effects of antimicrobial therapy on the genetic repertoire present in human microbial communities. In this study, we will examine changes in the microbiota as well as frequency of antibacterial resistance genes harbored in skin, saliva, and colonic microbiomes longitudinally in subjects on prolonged antimicrobial therapy, as well as household members of the person on antibiotic therapy. Previously well patients with minimal prior antibiotic exposure will be enrolled upon diagnosis of an infection requiring long-term antibiotic therapy, such as osteomyelitis or prosthetic joint infection, prior to starting antibiotic therapy. We will examine the microbiota of the skin, saliva, and gut prior to antibiotics as well as the frequency of antibiotic resistance genes harbored within these microbial communities. We will compare microbial communities and antibiotic resistance gene frequencies before, during and after prolonged course of antibiotics in patients on antibiotics. We will also look for alterations that occur among microbiomes or antibiotic resistance genes among household members of people on antibiotics.

详细描述

Commensal flora are thought to play important roles in maintaining human health. Bacterial communities and the antibiotic resistance genes harbored within them are likely altered by selective pressure imposed by antibiotic use in clinical settings. Perturbations to the endogenous microbial communities as a result of antibiotic use may have a significant impact on the microbiome and the antibiotic resistance genes carried within. We aim to study how microbial communities are altered by prolonged antibiotic therapy using metagenomics techniques. In addition to measuring the diversity of bacterial genotypes present, we plan to characterize the repertoire of antibiotic resistance genes in human subjects exposed to prolonged courses of antibiotics. We also will measure the effect of environment on the antibiotic resistance repertoire of human microbial communities by assessing antibiotic genes present in subjects that reside in the same household compared to other subjects.

Aim 1: To improve our understanding of the effects of prolonged antibiotic courses on native bacterial communities of human skin, mouth, and colon during and after therapeutic courses of antibiotics. We will look at alterations in bacterial diversity within these communities in quantity as well as quality (how classes of bacteria are altered) using metagenomics.

Aim 2: To improve our understanding of effects of prolonged antibiotic use on the presence of antibiotic resistance genes in the human microbiome over time. We will follow presence and diversity and quantity of antibiotic resistance genes present in commensal bacterial communities longitudinally before, during, and following prolonged antibiotic courses.

Aim 3: To assess whether the bacterial communities present in members of the same household are changed as a result of environmental influences rather than direct antibiotic administration.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Basic Science
盲法
None

入排标准

年龄范围
18 Years 至 75 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Age 18-75
  • Capacity to give consent, provide samples, and follow-up at routine clinic appointments

排除标准

  • Antibiotic use (outside of 72 hour period prior to diagnosis or peri-operative short course) within the 3 months prior to enrollment
  • Unable to provide consent or samples
  • immunocompromised conditions such as HIV/AIDS, SLE, organ or bone marrow transplant recipient, on immunosuppressants for autoimmune disease, genetic disorders such as cystic fibrosis that may result in substantial alteration in colonized community.
  • inability to provide 3mL of saliva without stimulation
  • critical illness

研究组 & 干预措施

Amoxicillin

Experimental

24 participants received amoxicillin for 3 or 7 days

干预措施: Antibiotic administration (Drug)

Azithromycin

Experimental

24 participants received azithromycin for 3 or 7 days

干预措施: Antibiotic administration (Drug)

结局指标

主要结局

Microbiome

时间窗: 6 months

Individuals received 3 or 7 days of antibiotics and were followed for 6 months

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

David Pride

Associate Professor

University of California, San Diego

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