Orthopaedic Trauma Infections
Conditions
Keywords
Infection, Nonunion, Fracture healing
Brief summary
The purpose of this research project is to improve understanding of the potential role of highly sensitive bacterial tests in diagnosing infected non-healing fractures compared to the current standard of care, microbiologic culture (growing bacteria from tissue specimens in the laboratory). In order to understand the validity of the highly sensitive tests, parameters of the test in different groups of patients must be established. This study is examining how two highly sensitive tests compare to each other and to the standard of care (microbiologic culture) in three groups of patients. Group 1 is clean broken bone surgery undergoing plate and screw fixation, intramedullary nailing fixation where the fracture site is accessible, or staged treatment of a broken bones initially treated by joint spanning external fixation device. Group 2 will include patients having a plate and screws removed without clinical evidence of infection. Group 3 will be patients undergoing an initial procedure for fracture nonunion.
Detailed description
Infected, broken bones that do not heal are a difficult clinical problem that significantly affect patient quality of life. Current methodology for detecting bacteria (growth in laboratory cultures) is inadequate to detect infections caused by bacteria existing in a biofilm, which is the layer of slime found in the presence of foreign bodies (eg, implanted metal devices to fix broken bones). Advances in molecular biology have allowed development of highly sensitive tests to detect bacteria in the biofilm state. However, the limited prior research has not included control groups or compared the performance of different highly sensitive tests. To address these limitations and further define the role of highly sensitive bacterial tests in clinical practice, the investigators hypothesize that there will be increasing bacterial burden when comparing clean broken bone surgery (1st surgery) to implanted metal device removal (2nd surgery, bone healed) to index nonunion surgery (subsequent surgery, bone not healed) as measured by percentage of cases being positive for bacteria using highly sensitive bacterial tests. Further, the highly sensitive bacterial tests (Illumina MiSeq system and Ibis T5000 biosensor) will have similar ability to quantify the number of bacteria and differentiate bacterial species. Eligible patients will consist of three groups. Group 1 is clean broken bone surgery undergoing plate and screw fixation, intramedullary nailing fixation where the fracture site is accessible, or staged treatment of a broken bones initially treated by joint spanning external fixation device. Group 2 will include patients having a plate and screws removed without clinical evidence of infection. Group 3 will be patients undergoing an initial procedure for fracture nonunion. Tissue obtained at the time of surgery will be sent to the research laboratory for culture and performance of the two highly sensitive tests. The tissue samples taken will be tissue normally removed and discarded in the course of these particular procedures. The rates of positivity for culture and the highly sensitive tests will be compared amongst the three groups. Investigators will also compare bacterial count and the distribution of bacterial species found using the two highly sensitive tests. These data will then undergo statistical analysis against clinical data gathered from review of the patients' charts. The overall project goal is to establish the clinical relevance of highly sensitive bacterial tests in diagnosing infected nonunions. The ability to more accurately identify patients with infection may lead to a change in clinical decision making with respect to surgical procedure or antibiotic treatment. This project will develop an improved understanding of the potential role of highly sensitive bacterial tests in diagnosing infected nonunions compared to the current standard of care, which is growing bacteria in the laboratory under artificial conditions.
Interventions
DIAGNOSTIC_TESTHighly Sensitive Assays
Tissue will be collected at the time of surgery from patients in each arm of the study. In addition to tissue stored in RNAlater and sent to a research laboratory, cultures will also be sent to Quest Diagnostics for independent culture results.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Closed fracture undergoing open reduction internal fixation, intramedullary nailing (IMN) where the fracture site is accessible, or staged treatment of a pilon or plateau that was initially treated by joint spanning external fixation. * Plate and screw removal without clinical evidence of infection * Index procedure for fracture nonunion
Exclusion criteria
* Index fracture surgery for an open fracture or intramedullary nailing with fracture site not accessible * Hardware removal if fracture not already healed * Index nonunion surgery being bone grafting of a 'critical' defect * Pregnant females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tissue Samples Identified With Bacterial DNA According to Highly Sensitive Bacterial Assays | Study surgery to 6-month clinical follow-up | The objective of this research is to see if highly sensitive bacterial assays are useful for determining whether fracture nonunions are infected |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Closed Index Fractures Group 1 is clean, closed fractures undergoing index open reduction internal fixation (ORIF), intramedullary nailing (IMN) where the fracture site is accessible, or staged treatment of a pilon or plateau that was initially treated by joint spanning external fixation. Tissue obtained at the time of surgery will be sent to the research laboratory for culture and performance of the two highly sensitive assays.
Highly Sensitive Assays: Tissue will be collected at the time of surgery from patients in each arm of the study. In addition to tissue stored in RNAlater and sent to a research laboratory, cultures will also be sent to Quest Diagnostics for independent culture results. | 43 |
| Group 2: Hardware Removal From Healed Fractures Group 2 will include patients having a plate removed from a healed fracture without clinical evidence of infection and excluding history of open fracture. Tissue obtained at the time of surgery will be sent to the research laboratory for culture and performance of the two highly sensitive assays.
Highly Sensitive Assays: Tissue will be collected at the time of surgery from patients in each arm of the study. In addition to tissue stored in RNAlater and sent to a research laboratory, cultures will also be sent to Quest Diagnostics for independent culture results. | 41 |
| Group 3: Index Treatment of Fracture Nonunions Group 3 will be patients that are undergoing an index procedure for fracture nonunion at a site where prior surgery has been undertaken for the fracture. Exclusions include bone grafting of 'critical' defects, active clinical infection, or \< 3 months from index fracture fixation. Tissue obtained at the time of surgery will be sent to the research laboratory for culture and performance of the two highly sensitive assays.
Highly Sensitive Assays: Tissue will be collected at the time of surgery from patients in each arm of the study. In addition to tissue stored in RNAlater and sent to a research laboratory, cultures will also be sent to Quest Diagnostics for independent culture results. | 27 |
| Total | 111 |
Baseline characteristics
| Characteristic | Group 1: Closed Index Fractures | Group 2: Hardware Removal From Healed Fractures | Group 3: Index Treatment of Fracture Nonunions | Total |
|---|---|---|---|---|
| Age, Continuous | 43 years STANDARD_DEVIATION 19 | 46 years STANDARD_DEVIATION 15 | 47 years STANDARD_DEVIATION 14 | 45 years STANDARD_DEVIATION 21 |
| ASA Physical Status Classification System | 2.1 units on a scale STANDARD_DEVIATION 0.7 | 2.0 units on a scale STANDARD_DEVIATION 0.8 | 2.2 units on a scale STANDARD_DEVIATION 0.5 | 2.1 units on a scale STANDARD_DEVIATION 0.8 |
| Compartment Syndrome | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| High Energy Injury | 32 Participants | 32 Participants | 17 Participants | 81 Participants |
| Open Fracture | NA Participants | 4 Participants | 18 Participants | NA Participants |
| Pre-operative Antibiotics Administered | 43 Participants | 40 Participants | 26 Participants | 109 Participants |
| Race/Ethnicity, Customized Caucasian | 29 participants | 31 participants | 21 participants | 81 participants |
| Sex: Female, Male Female | 19 Participants | 21 Participants | 10 Participants | 50 Participants |
| Sex: Female, Male Male | 24 Participants | 20 Participants | 17 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 41 | 1 / 27 |
| other Total, other adverse events | 0 / 43 | 0 / 41 | 0 / 27 |
| serious Total, serious adverse events | 0 / 43 | 0 / 41 | 0 / 27 |
Outcome results
Primary
Number of Participants With Tissue Samples Identified With Bacterial DNA According to Highly Sensitive Bacterial Assays
The objective of this research is to see if highly sensitive bacterial assays are useful for determining whether fracture nonunions are infected
Time frame: Study surgery to 6-month clinical follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Closed Index Fractures | Number of Participants With Tissue Samples Identified With Bacterial DNA According to Highly Sensitive Bacterial Assays | 10 Participants |
| Group 2: Hardware Removal From Healed Fractures | Number of Participants With Tissue Samples Identified With Bacterial DNA According to Highly Sensitive Bacterial Assays | 24 Participants |
| Group 3: Index Treatment of Fracture Nonunions | Number of Participants With Tissue Samples Identified With Bacterial DNA According to Highly Sensitive Bacterial Assays | 20 Participants |