Impact of Prolonged Antibiotic Therapy on Commensal Microbial Community Gene Expression.
Primary Purpose
Microbial Colonization
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Antibiotic administration
Sponsored by
About this trial
This is an interventional basic science trial for Microbial Colonization
Eligibility Criteria
Inclusion Criteria:
- Age 18-75
- Capacity to give consent, provide samples, and follow-up at routine clinic appointments
Exclusion Criteria:
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Azithromycin
Amoxicillin
Arm Description
24 participants received azithromycin for 3 or 7 days
24 participants received amoxicillin for 3 or 7 days
Outcomes
Primary Outcome Measures
Microbiome
Individuals received 3 or 7 days of antibiotics and were followed for 6 months
Secondary Outcome Measures
Full Information
NCT ID
NCT05169255
First Posted
December 9, 2021
Last Updated
December 9, 2021
Sponsor
University of California, San Diego
1. Study Identification
Unique Protocol Identification Number
NCT05169255
Brief Title
Impact of Prolonged Antibiotic Therapy on Commensal Microbial Community Gene Expression.
Official Title
Long Term Antibiotics Study
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
December 7, 2012 (Actual)
Primary Completion Date
April 22, 2016 (Actual)
Study Completion Date
April 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Microbial Colonization
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two parallel groups with placebo versus antibiotics
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Azithromycin
Arm Type
Experimental
Arm Description
24 participants received azithromycin for 3 or 7 days
Arm Title
Amoxicillin
Arm Type
Experimental
Arm Description
24 participants received amoxicillin for 3 or 7 days
Intervention Type
Drug
Intervention Name(s)
Antibiotic administration
Intervention Description
Individuals received either azithromycin or amoxicillin for 3 or 7 days
Primary Outcome Measure Information:
Title
Microbiome
Description
Individuals received 3 or 7 days of antibiotics and were followed for 6 months
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18-75
Capacity to give consent, provide samples, and follow-up at routine clinic appointments
Exclusion Criteria:
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
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27912785
Citation
Ly M, Jones MB, Abeles SR, Santiago-Rodriguez TM, Gao J, Chan IC, Ghose C, Pride DT. Transmission of viruses via our microbiomes. Microbiome. 2016 Dec 2;4(1):64. doi: 10.1186/s40168-016-0212-z.
Results Reference
result
PubMed Identifier
27473422
Citation
Abeles SR, Jones MB, Santiago-Rodriguez TM, Ly M, Klitgord N, Yooseph S, Nelson KE, Pride DT. Microbial diversity in individuals and their household contacts following typical antibiotic courses. Microbiome. 2016 Jul 30;4(1):39. doi: 10.1186/s40168-016-0187-9.
Results Reference
result
Learn more about this trial
Impact of Prolonged Antibiotic Therapy on Commensal Microbial Community Gene Expression.
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