Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage (Bioburden)

Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage: Correlation With Subsequent Post-Closure Deep Wound Infection: Bioburden Study

The purpose of this study is to characterize the bacteria in the wound "bioburden" at the time of definitive wound coverage/closure of severe tibia fractures in both the military and civilian populations.

Study Overview

• Status: Completed
• Conditions: Open Fracture

Detailed Description

Infection remains the most common and significant complication following high energy fractures. The strategies used in the prevention of deep infection following severe open fracture wounds have remained constant for the past 20 years.

This project is designed to analyze the microbiology profiles of wounds from severe tibia fractures at closure by comparing two methods: routine microbiology techniques and PCR methods using the Ibis T5000 Biosensor System. The results from both identification methods will be compared to the pathogens associated with deep surgical site infections that occur post closure of the wound. Currently it is unknown which of these methods will yield information that can lower complication rates and better function of the leg. Our goal is to perform a multi-center, prospective cohort study of wound bacterial bioburden and associated antibiotic care in severe open lower extremity fractures.

Primary Aim: In a subset of 60 patients, compare the bioburden, as detected by Ibis technology, from each of three sampling techniques (deep tissue; soft tissue composite; composite of tissue from the length and depth of the wound). Samples obtained using the most effective technique identified in this step will be processed using Ibis in subsequent tissue analysis. Effectiveness is defined as the ability to identify key wound infection-causing pathogens.

Primary Hypothesis: The composite sampling approach will be the most effective technique.

Secondary Aim: Characterize the wound bioburden at the time of definitive wound closure or coverage using the Ibis T5000 Biosensor System PCR technology as compared to standard microbiology techniques.

Hypothesis 2: The Ibis technology will detect more species of pathogens than standard microbiology techniques. The percent of patients for whom Ibis will detect all species identified by standard microbiology will be greater than 95%.

Specific Aim 3: Characterize the wound bioburden in the patients who develop deep infection within one year of wound closure, and determine the association between infecting pathogens with initial wound closure bioburden as measured jointly by Ibis and standard microbiology techniques.

Specific Aim 4: Document the variability in antibiotic selection and duration, and examine the impact of this selection on subsequent deep infection.

Hypothesis 4a: Among patients treated with antibiotic regimens that are appropriate for the pathogens identified by standard microbiology, there will be a lower probability of deep infection than among those patients who received inappropriate antibiotic regimens.

Hypothesis 4b: Among patients treated with antibiotic regimens that are appropriate for the pathogens identified by Ibis, there will be a lower probability of deep infection than among those patients who received inappropriate antibiotic regimens.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92134
      • Naval Medical Center San Diego
    • San Francisco, California, United States, 94115
      • UCSF Medical Center
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health and Hospital Authority
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Ryder Trauma Center
    • Tampa, Florida, United States, 33606
      • Florida Orthopaedic Institute
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University Dept of Orthopaedics
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Orthoindy at St Vincent
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, R Adams Cowley Shock Trauma Center
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
    • Bethesda, Maryland, United States, 20889
      • Walter Reed Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Orthopaedic Associates of Michigan, Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center / Minneapolis
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28232
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
    • Winston-Salem, North Carolina, United States, 27157-1070
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University M.S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hosptial
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University/Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234-6315
      • San Antonio Miliary Medical Center
    • Houston, Texas, United States, 77030
      • UT Health: The University of Texas Health Science Center at Houston Medical School
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Portsmouth, Virginia, United States, 23708
      • Naval Medical Center Portsmouth
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Particiapting METRC Trauma Centers across the country.

Description

Inclusion Criteria:

1. All open Grade III tibia fractures (plateau, shaft, pilon) requiring a second procedure following fixation, or traumatic transtibial amputations requiring delayed primary closure, skin grafting and/ or flap coverage.
2. Ages 18 - 64 years inclusive
3. Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
4. Patients may have a traumatic brain injury.
5. Patients may have other fractures including spine, upper extremity fractures, contralateral lower extremity injuries, ipsilateral pelvis, hip, femur or foot injuries.
6. Patients may be treated initially at an outside institution prior to transfer to the study institution, as long as the definitive fixation was not performed prior to entrance into the study.
7. Patients with bilateral injuries that meet inclusion criteria may be included, but only the limb rated as "more severe" by the treating surgeon will be enrolled in the study.
8. Patients may have co-existing non-tibial infection, with or without antibiotic treatment.
9. Patients may have an existing infection of the surgical wound under treatment at the time of wound closure.
10. Patients may be definitively fixed using any method (nail, plate, ex fix)
11. Patients may have a fasciotomy

Exclusion Criteria:

1. Patient speaks neither English nor Spanish
2. Patient is a prisoner
3. Patient has been diagnosed with a severe psychiatric condition
4. Patient is intellectually challenged without adequate family support
5. Patient lives outside the hospital's catchment area
6. Patients with planned follow-up at another medical center

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
severe open fractures of the tibia bone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection	The presence of a deep surgical site infection will be defined by the criteria of the Centers for Disease Control. Deep SSI occurs within 30 days after the operation if no implant is left in place, or within one year if implant is in place and the infection appears to be related to the operation.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Classification of Appropriate Antibiotic Care	An expert panel consisting of the study PI, two additional orthopaedic trauma surgeons and at least three infectious disease experts will be convened to develop a classification grid for the most common and/or expected microbial species to be found in this study and the related antibiotic treatment regimens used in the initial care of these patients. For each microbial species, the expert panel will classify a given antibiotic regimen as "appropriate" and "not appropriate", based on the best available published data.	1 year

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Michael J Bosse, MD, Carolinas Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: November 7, 2011
• First Submitted That Met QC Criteria: December 20, 2011
• First Posted (Estimate): December 21, 2011

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: infections; open fracture wounds; tibia fractures; antibiotic therapies in severe fractures; All severe open fracture of the tibia bone
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Fractures, Open
• Other Study ID Numbers: A-15737.5a