Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO)

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.

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.