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.
