Healthy Patients & Effect of Antibiotics

NCT03098485 | Completed Results

• 1 other identifier: 201610071
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the impact of antimicrobial (antibiotic) exposures on the microbiome in healthy adults, specifically during and after usual courses of the antimicrobials used to treat community acquired pneumonia (CAP). Pneumonia is a lung infection, and community-acquired pneumonia is pneumonia that develops outside of a healthcare facility (i.e., in the community). A microbiome is a the community of microorganisms living in a particular location, such as the gut or the mouth. Disruptions to a person's microbiome may reduce his/her "colonization resistance" (resistance to colonization with pathogenic microorganisms) and make him/her more susceptible to multidrug resistant organism (MDRO) colonization and infection. To study changes in the microbiome, the investigators will recruit 20 healthy adult volunteers and obtain fecal, salivary, skin, and urine specimens at multiple time points before, during, and after administration of antimicrobials. Participants will be randomized to one of 4 antimicrobial regimens, all of which are FDA-approved for treatment of community-acquired pneumonia. Stool specimens will be analyzed via stool culture and genetic sequencing, and all remaining specimens will be frozen and used to create a biospecimen repository for future analysis. The rationale for using healthy volunteers (instead of patients already prescribed antibiotics by their physicians) is because the human microbiome is very complex and can be affected by a variety of medical conditions and other medications. In addition, the presence or absence of patient-specific factors means people with infections may not be prescribed the specific courses of antibiotics the investigators are trying to study. Studying the effect of antibiotics on healthy volunteers will provide baseline data that are more applicable to the population at large.

Conditions

Microbiota; Anti-bacterial Agents

Outcome Measures

Primary Outcomes (3)

• Degree of Microbial Disruption: Number of Patients With Recovery of Bacterial Species Richness at 185 Days Post-antibiotics

  The degree of microbial disruption will be defined by recovery of bacterial species richness (number of species) after antibiotics.

  Decrease from baseline (7 days prior to antibiotics) in microbial diversity at 185 days post-antibiotics

• Degree of Microbial Disruption: Number of Patients With Increase in Antibiotic Resistance Genes at 185 Days Post-antibiotics

  The degree of microbiome disruptions will be defined by an increase in the number of antibiotic resistance genes after antibiotics compared to baseline.

  Increase from baseline (7 days prior to antibiotics) in antibiotic resistance genes at 185 days post-antibiotics

• Degree of Microbial Disruption: Number of Patients With Continued Microbial Disruption at 185 Days Post-antibiotics

  The degree of microbiome disruptions will be defined by continuing microbial disruption, as measured by Bray-Curtis dissimilarity, post-antibiotics compared to baseline.

  Persistent disruption from baseline (7 days prior to antibiotics) in microbial composition at 185 days post-antibiotics

Study Arms (4)

Levofloxacin

EXPERIMENTAL

1 750mg tab of levofloxacin by mouth for 5 days

Drug: Levofloxacin

Azithromycin

EXPERIMENTAL

1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days)

Drug: Azithromycin

Cefpodoxime

EXPERIMENTAL

200mg tab by mouth twice per day for 5 days

Drug: Cefpodoxime

Azithromycin and cefpodoxime

EXPERIMENTAL

Azithromycin: 1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days) Cefpodoxime: 200mg tab by mouth twice per day for 5 days

Drug: Azithromycin; Drug: Cefpodoxime

Interventions

Levofloxacin DRUG

5 days of levofloxacin administration

Also known as: Levaquin, Quixin, Iquix

Levofloxacin

Azithromycin DRUG

5 days of azithromycin administration

Also known as: Zithromax, AzaSite, Zmax

Azithromycin; Azithromycin and cefpodoxime

Cefpodoxime DRUG

5 days of cefpodoxime administration

Also known as: Vantin

Azithromycin and cefpodoxime; Cefpodoxime

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults ages 21-60 residing in the St. Louis, Missouri, USA metropolitan area

You may not qualify if:

• History of allergic reaction to study antimicrobial(s)
• Contraindication(s) to study antimicrobial(s)
• Inability to provide regular stool samples
• Any non-topical antimicrobial exposure in previous 6 months
• Tube feeds as primary source of nutrition in previous 6 months
• Pregnant or risk of becoming pregnant during study period
• Breastfeeding during study period
• Gastroenteritis in last 3 months
• Any non-elective hospitalization in the previous 12 months
• Incontinent of stool
• Known colonization with an MDRO
• Anticipated change in diet or medications during study period
• Elective surgery during study period
• History of an intestinal disorder
• Inability to provide written, informed consent

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Interventions

Levofloxacin; Ofloxacin; Azithromycin; Cefpodoxime; Cefpodoxime Proxetil

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds

Results Point of Contact

• Title: Kimberly Reske, MPH
• Organization: Washington University in St. Louis School of Medicine

kreske@wustl.edu

3147474041

Study Officials

• Jennie H. Kwon, DO, MSCI

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: March 31, 2017
• Study Start: January 1, 2017
• Primary Completion: August 30, 2022
• Study Completion: August 30, 2022
• Last Updated: November 10, 2022
• Results First Posted: November 10, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)