Impact of Mupirocin Decolonization on the Nasal Microbiome

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by VA Eastern Colorado Health Care System
Sponsor:
Information provided by (Responsible Party):
VA Eastern Colorado Health Care System
ClinicalTrials.gov Identifier:
NCT02045329
First received: January 22, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

The normal bacteria that inhabit the human nose, also known as the nasal microbiome, may serve as a host defense mechanism against colonization and infection by Staphylococcus aureus, including methicillin resistant S. aureus (MRSA). Mupirocin is a topical antibacterial agent that may be used to clear nasal colonization with S. aureus, and reduce risk of S. aureus infection. The impact of mupirocin on the normal nasal microbiome is not known. We hypothesize that the nasal microbiome is changed by mupirocin. Our study aims to define the nasal microbiome before and after decolonization therapy with mupirocin.


Condition
Nasal Colonization With Staph Aureus

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Impact of Mupirocin Decolonization on the Nasal Microbiome

Resource links provided by NLM:


Further study details as provided by VA Eastern Colorado Health Care System:

Primary Outcome Measures:
  • Nasal microbiome changes with mupirocin [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    This is a descriptive study. We will define the nasal microbiota before and after decolonization therapy with mupirocin.


Secondary Outcome Measures:
  • Recurrence of S. aureus colonization [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    We will look at differences in the nasal microbiome of subjects who realpse with colonization and those who remain free of S. aureus colonization.


Biospecimen Retention:   Samples With DNA

Nasal swabs


Estimated Enrollment: 60
Study Start Date: October 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Staphylococcus aureus nasal carriers
Patients who are treated with mupirocin to clear nasal colonization with Staphylococcus aureus

Detailed Description:

A. Outcome Measures: This is essentially a descriptive study. We will define the nasal microbiota before and after decolonization therapy with mupirocin.

B. Description of Population to be Enrolled: Patients at VA-Denver who are starting a course of nasal mupirocin therapy for S. aureus decolonization will be enrolled. The common indications for decolonization therapy are preparation for joint replacement surgery and to facilitate removing patient from isolation for a prolonged stay on the rehabilitation service. Written informed consent will be obtained.

C. Study design and research methods: A nasal swab will be obtained just prior to initiation of mupirocin therapy, within 48 hours of the completion of mupirocin therapy, one week, two weeks, four weeks, eight weeks, and 16 weeks following the completion of mupirocin therapy. The swab will be inserted into one nare and rotated for 3 seconds. The procedure will be repeated on the other nare. The two heads will be refrigerated immediately, and held at 2-5o C until they can be placed into sterile micro tubes for storage at -80o C. A separate swab will be passed through the mouth and rubbed over the tonsils and posterior oropharynx , and stored in the same fashion.

Broad-Range PCR and High throughput DNA Sequencing PCR amplification and sequencing of rRNA genes will follow our previously published protocol (13). In brief, DNA lysates are subjected to PCR with pan-bacterial 16S rDNA rDNA primers, which yields libraries of PCR amplicons representative of all bacteria or fungi in a specimen (14). Triplicate PCR reactions will be performed and amplicons pooled for each sample. Poisoning controls spiked with bacterial (e.g. Bacillus subtilis) genomic DNA will be assayed to detect the presence of PCR inhibitors in template DNA preparations; although not typically a problem with nasal swabs, inhibitory samples will be purified by ethanol precipitation and then resubmitted for PCR. PCR amplicon libraries will be sequenced using the high-throughput Illumina MiSeq personal sequencing platform. which is available through the University of Colorado's Division of Infectious Diseases. This platform can generate 5-20x106 DNA sequences in a single instrument run with mean read lengths ~450 nts. The primers used for broad-range PCR include unique barcoded sequences in order to simultaneously sequence multiple amplicon libraries in a single instrument run (15). We will construct and sequence libraries from 100 specimens (50 persistent MRSA carriers [cases] and 50 non-carriers [controls]) to a depth of >50,000 high-quality sequencing reads per specimen. Our preliminary study indicates that this depth of coverage will represent a complete survey of the nares microbiota for each specimen.

Sequence Analysis Microbes present in specimens will be identified through use of the Naïve Bayesian Classifier Tool (16) of the Ribosomal Database Project (17). To reduce the overall complexity of the datasets, similar rDNA sequences will be clustered into operational taxonomic units (OTUs) by clustering sequences based on taxonomic assignments. Data matrices are then assembled that tabulate the frequency of each OTU in a sample. Sampling coverage for each amplicon library will be estimated (18-20) and additional sequences screened if coverage is less than 95%. All sequences will be deposited into GenBank for public use.

Validation of candidate microorganisms Microbes identified through broad-range rDNA analysis as potentially impacting S. aureus colonization will be further evaluated based on targeted QPCR measurements. Based on our preliminary results and previously published studies that suggest their interference with S. aureus growth, both S. epidermidis, (femA) and Corynebacterium spp., (rpoB PCR) will be enumerated by Q-PCR (Table, below). Primer sets for Q-PCR assays of novel microbial groups will be designed for detection of rDNA operons (i.e. 16S-ITS-23S genes) through the ARB software package (21). In the case of previously recognized microbial groups and/or species, PCR primer sets may be identified by literature search.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who are treated with mupirocin to clear nasal colonization with Staphylococcus aureus

Criteria

Inclusion Criteria: - Patients at VA-ECHCS who are starting a course of nasal mupirocin therapy for S. aureus decolonization

Exclusion Criteria:

Age < 18 years Pregnant women Prisoners Decisionally challenged subjects

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02045329

Contacts
Contact: Mary T Bessesen, MD 303-393-2837 mary.bessesen@va.gov
Contact: Jill C Adams, BSN 303-399-8020 ext 6862 Jill.Adams@va.gov

Locations
United States, Colorado
Veterans Affairs Eastern Colorado Healthcare System Recruiting
Denver, Colorado, United States, 80220
Contact: Mary T Bessesen, MD    303-393-2837    Mary.Bessesen@va.gov   
Contact: Jill C Adams, BSN    303-399-8020 ext 6862    Jill.Adams@va.gov   
Principal Investigator: Mary T Bessesen, MD         
Sponsors and Collaborators
VA Eastern Colorado Health Care System
Investigators
Principal Investigator: Mary T Bessesen, MD Veterans Affairs Eastern Colorado Healthcare System
  More Information

Publications:
Responsible Party: VA Eastern Colorado Health Care System
ClinicalTrials.gov Identifier: NCT02045329     History of Changes
Other Study ID Numbers: COMIRB 13-1513, Grant funding
Study First Received: January 22, 2014
Last Updated: January 22, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by VA Eastern Colorado Health Care System:
Staphylococcus aureus, mupirocin, decolonization

Additional relevant MeSH terms:
Mupirocin
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014