Healthy Patients & Effect of Antibiotics

NCT ID: NCT03098485

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2022-08-30

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.

Detailed 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.

Conditions

Microbiota; Anti-bacterial Agents

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Levofloxacin

1 750mg tab of levofloxacin by mouth for 5 days

Group Type: EXPERIMENTAL

Levofloxacin

Intervention Type: DRUG

5 days of levofloxacin administration

Azithromycin

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

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

5 days of azithromycin administration

Cefpodoxime

200mg tab by mouth twice per day for 5 days

Group Type: EXPERIMENTAL

Cefpodoxime

Intervention Type: DRUG

5 days of cefpodoxime administration

Azithromycin and cefpodoxime

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

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

5 days of azithromycin administration

Cefpodoxime

Intervention Type: DRUG

5 days of cefpodoxime administration

Interventions

Levofloxacin

5 days of levofloxacin administration

Intervention Type: DRUG

Azithromycin

5 days of azithromycin administration

Intervention Type: DRUG

Cefpodoxime

5 days of cefpodoxime administration

Intervention Type: DRUG

Other Intervention Names

Levaquin, Quixin, Iquix; Zithromax, AzaSite, Zmax; Vantin

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennie H. Kwon, DO, MSCI

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201610071

Identifier Type: -

Identifier Source: org_study_id