MICRO Study: Detecting Bacterial Infections Related to Orthopaedic Surgical Implants (MICRO)

Early Determination of Biofilm Formation on Orthopaedic Devices

A prospective trial conducted at Shock Trauma of patients between 18 years of age and older who have sustained a fracture with metal implanted. The investigators will be collecting between 1-3 routine blood draws for the purpose of laboratory analysis to assess biofilm growth. Patients may be infected or non-infected at the time of blood draw; they will be selected at random for purposes of this study. All patients will be followed as standard of care by their treating physician for all their follow up visits.

Study Overview

• Status: Completed
• Conditions: Open Reduction and Internal Fixation of Extremity Fractures
• Intervention / Treatment: Diagnostic test: Blood draws

Detailed Description

Surgical site infection in the orthopaedic surgery population is a significant public health issue. Wound infections result in both increased length of hospital stay and total cost of care.

Surgical site infection (SSI) is the most common preventable adverse outcome after a major operation. The economic costs to the US healthcare system are enormous estimated to be in excess of $1.8 billion per year. For patients who develop an SSI, the cost may be even higher with length of stay and risk of death doubled. Thus the benefits of any intervention decreasing the risk of SSI are very tangible.

A biofilm is a layer of bacteria that adheres to a surface; in Orthopaedics, this often means adherence to implanted metal after fracture surgery. The test that has been designed by one of the investigators on the study has been shown in an animal model to detect the formation of a biofilm up to 1 month prior to clinical detection. Having a blood assay such as this would allow earlier antibiotics and potentially prevent the need for further surgeries to remove metal implants and clean out the biofilm.

• Study Type: Observational
• Enrollment (Actual): 260

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Shock Trauma Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Trauma patients that were considered at risk for infection after fracture fixation. Inclusion criteria included open fractures, proximal tibia fractures, pilon fractures, and calcaneus fractures treated with surgical fixation.

Description

Inclusion Criteria:

• Previous fracture fixation with an implant (intramedullary nail, plate, screws), or joint revisions, or periprosthetic fracture, or admitted from orthopaedic trauma clinic due to infection, or inpatient with a known infection.
• English speaking

Exclusion Criteria:

• Patients with planned follow-up at another medical center
• Patient lives outside of the hospital catchment area

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infected; Trauma patients that were considered at risk for infection after fracture fixation. Inclusion criteria included open fractures, proximal tibia fractures, pilon fractures, and calcaneus fractures treated with surgical fixation. Each patient enrolled in the study provided 1-3 blood samples. These blood samples were tested using basic science techniques to determine the level of exposure to a staphylococcal biofilm each patient has experienced over a period of time. The only intervention patients experience are non-standard of care blood draws. The blood is then tested in a basic science laboratory. Patients were enrolled if presented as high risk but later separated into the Infected Group or the Not Infected Group based on whether or not they went on to develop an infection post surgery. All patients in this group went on to develop an infection.	Diagnostic test: Blood draws; The only intervention patients experience are non-standard of care blood draws. The blood is then tested in a basic science laboratory.
Not Infected; Trauma patients that were considered at risk for infection after fracture fixation. Inclusion criteria included open fractures, proximal tibia fractures, pilon fractures, and calcaneus fractures treated with surgical fixation. Each patient enrolled in the study provided 1-3 blood samples. These blood samples were tested using basic science techniques to determine the level of exposure to a staphylococcal biofilm each patient has experienced over a period of time. The only intervention patients experience are non-standard of care blood draws. The blood is then tested in a basic science laboratory. Patients were enrolled if presented as high risk but later separated into the Infected Group or the Not Infected Group based on whether or not they went on to develop an infection post surgery. All patients in this group did not go on to develop an infection.	Diagnostic test: Blood draws; The only intervention patients experience are non-standard of care blood draws. The blood is then tested in a basic science laboratory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Blood Samples With High Levels of Absorbance Via ELISA for Patients (Greater Than 1.5 Ratio Compared to Control Human Serum)	A high level of absorbance via ELISA (greater than 1.5 ratio compared to control human serum) is a positive test result. The rate of not infected patient samples that return positive will demonstrate the false positive rate of the test.	1 year of clinical follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Blood Samples With Low Levels of Absorbance Via ELISA for Patients (Greater Than 1.5 Ratio Compared to Control Human Serum)	A low level of absorbance via ELISA (greater than 1.5 ratio compared to control human serum) is a negative test result. The rate of infected patient samples that return negative will demonstrate the false negative rate of the test.	1 year of clinical follow-up

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Publications and helpful links

General Publications

• Prabhakara R, Harro JM, Leid JG, Harris M, Shirtliff ME. Murine immune response to a chronic Staphylococcus aureus biofilm infection. Infect Immun. 2011 Apr;79(4):1789-96. doi: 10.1128/IAI.01386-10. Epub 2011 Jan 31.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: April 7, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Infection; Methicillin-resistant Staphylococcus aureus (MRSA); Biofilm Assay
• Other Study ID Numbers: HP-00055743