Impact of Prolonged Antibiotic Therapy on Commensal Microbial Community Gene Expression.
Condition: Microbial Colonization
MeSH terms: Communicable Diseases; Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Antibiotic administration
Intervention type(s): Drug
Intervention description(s): Individuals received either azithromycin or amoxicillin for 3 or 7 days
Intervention MeSH terms: Anti-Bacterial Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two parallel groups with placebo versus antibiotics
Masking: None (Open Label)
Primary purpose: Basic Science