Impact of Prolonged Antibiotic Therapy on Commensal Microbial Community Gene Expression.

NCT05169255 | Completed Phase 3

• 1 other identifier: 121456
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Microbial Colonization

Outcome Measures

Primary Outcomes (1)

• Microbiome

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

  6 months

Study Arms (2)

Azithromycin

EXPERIMENTAL

24 participants received azithromycin for 3 or 7 days

Drug: Antibiotic administration

Amoxicillin

EXPERIMENTAL

24 participants received amoxicillin for 3 or 7 days

Drug: Antibiotic administration

Interventions

Antibiotic administration DRUG

Individuals received either azithromycin or amoxicillin for 3 or 7 days

Amoxicillin; Azithromycin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Related Publications (3)

• 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.

  PMID: 27912785 RESULT

• 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.

  PMID: 27473422 RESULT

• Chopyk J, Cobian Guemes AG, Ramirez-Sanchez C, Attai H, Ly M, Jones MB, Liu R, Liu C, Yang K, Tu XM, Abeles SR, Nelson K, Pride DT. Common antibiotics, azithromycin and amoxicillin, affect gut metagenomics within a household. BMC Microbiol. 2023 Aug 2;23(1):206. doi: 10.1186/s12866-023-02949-z.

  PMID: 37528343 DERIVED

MeSH Terms

Conditions

Communicable Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Two parallel groups with placebo versus antibiotics

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: December 23, 2021
• Study Start: December 7, 2012
• Primary Completion: April 22, 2016
• Study Completion: April 22, 2016
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share