Post Operative Surgical Site Infection
Conditions
Keywords
Surgical site infection risk prevention, Bacterial species type and antibacterial sensitives
Brief summary
The Vancomycin Study is a multi-center, prospective randomized controlled trial that will compare the proportion of deep surgical site infections within 6 months in patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder at the time of fracture fixation.
Detailed description
Primary Aim: Compare the proportion of deep surgical site infections within 6 months in patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder. Primary Hypothesis: The proportion of deep surgical site infections will be lower for patients treated with local Vancomycin powder. Secondary Aim #1: Compare antibiotic sensitivities of the bacteria in the patients who develop deep surgical site infections in study patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder. Hypothesis 1: In the patients who develop infections, the antibiotic sensitivity profiles between patients treated with local Vancomycin powder will be non-inferior to those treated without local Vancomycin powder. Secondary Aim #2: Build and validate a risk prediction model for the development of deep surgical site infections in patients treated without local Vancomycin powder. (b) Explore whether the effect of local Vancomycin powder is modified by the predicted risk of infection. Hypothesis 2: Patient (e.g. medical co-morbidities) and injury (e.g open fractures) factors will be highly predictive of infection risk. Hypothesis 3: Patients with higher predictive risk will experience greater benefit from local antibiotics.
Interventions
DRUGVancomycin antibiotic powder
At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.
Sponsors
Major Extremity Trauma Research Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* All "high energy" tibial plateau fractures treated operatively with plate and screw fixation. * We define "high energy" tibial plateau fractures as patients who are either: * Initially treated with an external fixation (with or without limited internal fixation) and treated definitively more than 3 days later after swelling has resolved. * Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment. * Any tibial plateau fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds. * All "high energy" pilon (distal tibial plafond) fractures treated operatively with plate and screw fixation. We define "high energy" pilon fractures as patients who are either: * Initially treated with an external fixation (with or without fibula fixation or limited internal fixation) and treated definitively more than 3 days later after swelling has resolved. * Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment. * Any tibial pilon fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds. * Ages 18 to 80 years * Patients may have co-existing non-tibial infection, with or without antibiotic treatment. * Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections. * Patients may have a head injury * Patients may have a portion of the fixation (e.g. fibula fixation in pilon or percutaneous screws across a tibial plateau fracture) prior to definitive plate fixation, at the initial surgery before randomization. * Patients may have other orthopedic and non-orthopaedic injuries. * Patients may have pre-existing musculoskeletal injuries, be non ambulators, or have spinal cord injuries. * Women and minorities are included
Exclusion criteria
* The study injury: tibial plateau, pilon, is already infected at time of study enrollment. * Patient speaks neither English nor Spanish. * Patients who have already had definitive fixation prior to enrollment in the study. * Severe problems with maintaining follow-up (e.g. patients who are homeless at the time of injury or those how are intellectually challenged without adequate family support). * Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome). * Pregnancy. * The study injury is a type IIIB or IIIC open fracture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinically Significant Deep Surgical Site Infection (SSI) | 26 weeks | The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months. Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS). The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathogen Type | 26 weeks | This secondary outcome represents the type of bacteria or fungus isolated from the fracture site at the time of surgery for infection during the follow up period. Cultures were obtained using routine clinical sterile technique in the operating room and processed according to standard laboratory practices at each participating site. An infectious disease physician blinded to treatment arm reviewed and categorized all culture results. Pathogens were classified into five groups: gram-positive cocci, gram-positive rods, gram-negative rods, anaerobes, and fungi. The frequency of each pathogen type recovered was compared between patients who received topical vancomycin powder during surgery and those who did not. |
| Bacterial Susceptibility and Antimicrobial Resistance | 26 weeks | This secondary outcome characterizes the susceptibility of recovered pathogens to commonly used antibiotics collected at the time of surgery for infection during follow up. Antimicrobial susceptibility testing was performed by hospital laboratories using standard methods at each participating site. The pattern of susceptibility and resistance to various antimicrobial agents was compared between the two treatment groups to assess whether exposure to topical vancomycin powder was associated with differences in antibiotic resistance profiles, including the emergence of resistant organisms or other hard-to-treat pathogens. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRenan Castillo, PhD
Johns Hopkins Bloomberg School of Public Health
PRINCIPAL_INVESTIGATORRobert O'Toole, MD
University of Maryland R Adams Cowley Shock Trauma Center
STUDY_DIRECTORAnthony Carlini, MS
Johns Hopkins Bloomberg School of Public Health
Participant flow
Recruitment details
Approximately 1000 participants (500 per treatment arm) were enrolled across 36 METRC trauma centers over a 30-month period. Participants were recruited during the initial hospitalization for the their injury.
Participants by arm
| Arm | Count |
|---|---|
| Vancomycin Antibiotic Powder Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution.
In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.
Vancomycin antibiotic powder: At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure. | 481 |
| Standard of Care Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder. | 499 |
| Total | 980 |
Baseline characteristics
| Characteristic | Vancomycin Antibiotic Powder | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 14 | 46.1 years STANDARD_DEVIATION 13.5 | 45.75 years STANDARD_DEVIATION 13.8 |
| Race/Ethnicity, Customized Hispanic | 49 Participants | 58 Participants | 107 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 71 Participants | 77 Participants | 148 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 339 Participants | 346 Participants | 685 Participants |
| Race/Ethnicity, Customized Other | 19 Participants | 15 Participants | 34 Participants |
| Race/Ethnicity, Customized Refused/Unknown | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 182 Participants | 181 Participants | 363 Participants |
| Sex: Female, Male Male | 299 Participants | 318 Participants | 617 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 499 | 4 / 481 |
| other Total, other adverse events | 0 / 499 | 0 / 481 |
| serious Total, serious adverse events | 21 / 499 | 16 / 481 |
Outcome results
Primary
Number of Clinically Significant Deep Surgical Site Infection (SSI)
The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months. Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS). The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.
Time frame: 26 weeks
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Anerobe/fungal deep SSI | 1 surgical site infections |
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Contaminated sample | 0 surgical site infections |
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Total deep Surgical Site Infections | 29 surgical site infections |
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Culture negative deep SSI | 1 surgical site infections |
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Gram positive deep SSI | 17 surgical site infections |
| Vancomycin Antibotic Powder | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Gram negative deep SSI | 11 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Gram positive deep SSI | 36 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Anerobe/fungal deep SSI | 0 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Culture negative deep SSI | 1 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Contaminated sample | 1 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Gram negative deep SSI | 10 surgical site infections |
| Standard of Care | Number of Clinically Significant Deep Surgical Site Infection (SSI) | Total deep Surgical Site Infections | 48 surgical site infections |
Secondary
Bacterial Antibiotic Resistance Rate of Infected Participants
Secondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis. The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.
Time frame: 26 weeks
Secondary
Identify Risk Factors for Infection
A secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique. Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days. Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries. Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.
Time frame: 26 weeks