Using Microbial Genomics to Elucidate the Source of Central-line Associated Bloodstream Infections

Central line-associated bloodstream infections (CLABSIs) are the most common healthcare-associated infection in children and are associated with morbidity and mortality. This study will attempt to identify the source of bloodstream infections (BSIs) in children with CLABSI because we hypothesize that many of the BSIs that are currently classified as CLABSIs are actually laboratory-confirmed bloodstream infections (LCBI) that may be a result of mucosal barrier injury (MBI), also known as MBI-LCBI. In order to study this, we will isolate bacteria from multiple body sites of children that have BSI in order to compare these bacteria to the strain growing in their blood using whole-genome DNA sequencing. We will also evaluate biomarkers of MBI of the respiratory tract and GI tract.

Study Overview

• Status: Recruiting
• Conditions: Laboratory-confirmed Bloodstream Infection; Central Line-associated Bloodstream Infections; Mucosal Barrier Injury

Detailed Description

This is a prospective cohort pilot study at Boston Children's Hospital (BCH) that will explore the source of presumed CLABSI, which we believe may actually have multiple possible sources including MBI. We plan to enroll all inpatient children at BCH who meet the Centers for Disease Control and Prevention (CDC) definition of MBI-LCBI as well as children who meet the criteria for CLABSI without MBI. For all enrolled patients, we will collect samples from the oral cavity, respiratory tract, skin, and stool. These samples will be cultured in order to see if the same microbial species and strain(s) growing from the blood also grow from these other sites. Cultures will then have isolated colonies selected for whole-genome DNA sequencing to allow assessment of genomic diversity between body sites. Stool and blood samples will be tested for markers of MBI. All patient enrollment and sample collection will be done at BCH.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Rachel Bernier, MPH; Phone Number: 857-218-5348; Email: rachel.bernier@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Gregory Priebe, MD; Phone Number: 617-355-7327; Email: Gregory.Priebe@childrens.harvard.edu
      • Contact: Thomas Sandora, MD,MPH; Phone Number: 617-355-3858; Email: Thomas.Sandora@childrens.harvard.edu
      • Principal Investigator: Gregory Priebe, MD
      • Sub-Investigator: Thomas Sandora, MD, PhD
      • Sub-Investigator: Jennifer Blumenthal, MD
      • Sub-Investigator: Alexander McAdam, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with CLABSI

Description

Inclusion Criteria:

• Hospitalized at Boston Children's Hospital
• Central venous catheter of any type including peripherally inserted central catheters (PICC) in any location.
• Laboratory-confirmed bloodstream infection (LCBI) diagnosed by a clinical blood culture growing certain Gram-negative rods

Exclusion Criteria:

• Patients with CDC-defined secondary bloodstream infections

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Subject with suspected MBI
Subjects without suspected MBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phylogenetic relationships (on SNP scale) of bacteria isolated from different body sites	Phylogeny will be determined using whole-genome DNA sequences of multiple bacterial colonies that grow from each body site.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of biomarkers of MBI in the blood and stool (citrulline in blood, calprotectin in stool)	Low citrulline and high calprotectin indicate GI tract mucosal barrier injury.	Up to 2 years

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Gregory Priebe, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 17, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimated): October 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Central line-associated bloodstream infections; mucosal barrier injury; laboratory-confirmed bloodstream infection
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Infections; Communicable Diseases
• Other Study ID Numbers: P00012105