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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03098485
Other study ID # 201610071
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date January 2017
Est. completion date August 30, 2022

Study information

Verified date October 2022
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Each year, antimicrobial resistance causes over two million infections and 23,000 deaths in the US alone, representing a critical global public health issue. Some of the most feared multidrug resistant organisms (MDROs) include Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL), MDRO Acinetobacter, and MDRO Pseudomonas aeruginosa; there are few antimicrobials effective against these MDROs, and available antimicrobials often have rate-limiting toxicities. The major risk factor for MDRO colonization and subsequent MDRO infections is exposure to antimicrobials. The use of antimicrobials has been associated with an altered and often less diverse composition of the fecal microbiome, and expansion of the resistome. A "healthy" microbiome provides "colonization resistance" against potentially pathogenic bacteria; antimicrobials disrupt this protective community, providing selective pressure that favors MDRO colonization, persistence, and transmission to others. Methods to proactively prevent MDRO colonization, rather than reliance on reactive approaches to this problem, are urgently needed. Antimicrobial stewardship is a key component of MDRO prevention efforts; however, there is no method to determine which antimicrobials cause the greatest degree of microbiome disruption. A better understanding of exactly how antimicrobials alter the microbiome is necessary to optimally guide future MDRO prevention efforts and antimicrobial stewardship. The development of microbiome disruption indices (MDIs) would help characterize the risk associated with specific antimicrobials, and can be used during antimicrobial development, patient monitoring while on antimicrobials, and to facilitate infection prevention efforts to contain MDRO spread. Additionally, MDIs can be used as an alert when microbiome disruptions reach a critical level and MDRO colonization is imminent. At that point, interventions to restore the microbiome could be implemented. Community-acquired pneumonia (CAP) is one of the leading causes of death in the United States, with an estimated >900,000 cases each year in adults age 65 and older. Large amounts of antimicrobials are used in treating patients with CAP because the disease is relatively common. A better understanding of the effect of CAP antimicrobial treatment on the microbiome could result in improved treatment options for patients with CAP and protect CAP patients from colonization or infection with MDROs.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date August 30, 2022
Est. primary completion date August 30, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 21 Years to 60 Years
Eligibility Inclusion Criteria: - Healthy adults ages 21-60 residing in the St. Louis, Missouri, USA metropolitan area Exclusion Criteria: - 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Levofloxacin
5 days of levofloxacin administration
Azithromycin
5 days of azithromycin administration
Cefpodoxime
5 days of cefpodoxime administration

Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (1)

Lead Sponsor Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
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