Evaluation of a New Strategy for Protocolized Antibiotic Care for Severe Open Fractures: SEXTANT 2

Specific Aim 1: To determine if the SEXTANT treatment strategy designed to address the modern wound bioburden at the time of delayed wound closure/coverage is superior to the standard-of-care (SOC) antibiotic protocol. Our primary comparison will be the proportion of fracture-related infections (FRI) under the SEXTANT arm versus the FRI proportion for those under standard of care in the first 180 days following final wound closure/coverage. One-year rates of FRI will also be assessed.

Secondary Aims:

To compare rates of antibiotic-related complications (including aseptic nonunion) and serious adverse events (SAEs), including emergence of antibiotic-resistant pathogens, of the two treatment groups in the first 180 days following final wound closure/coverage. One-year rates will also be assessed.

To compare the terminal bioburden of the wounds at the time of delayed closure/coverage as sampled by standard tissue microbiology and assess the effectiveness of the antibiotic regimen.

(Exploratory) To employ emerging NextGen Sequencing rapid PCR platforms for wound pathogen identification in a sub-cohort of patients.

Inclusion criteria

• Injury meeting at least one of the following criteria:

a. Gustilo type III fractures of the tibia (OTA 41 plateau, OTA 42 shaft and OTA 43 pilon); ankle (OTA 44); calcaneus (OTA 82) and/or talus (OTA 81) with injury characteristics meeting at least one of the following criteria: i. All IIIB fractures ii. IIIA fractures that require a planned second debridement prior to definitive closure / coverage iii. IIIA fractures with extensive contamination or muscle damage precluding definitive internal fixation at the time of initial surgery iv. IIIA fractures with extensive degloving or wound greater than 10 cm after debridement (if indicated, primary wound closure is allowed. Primary wound closure refers to the definitive closure of the wound at the initial surgical event, without plans for re-entry for additional debridement and/or fracture fixation) v. IIIA fractures severe fracture comminution resulting from high energy trauma (if indicated, primary wound closure/coverage is allowed) vi. IIIA fractures with AO/OTA OFC contamination level of severe with material imbedded into bone or soft tissue or with a severe high risk environmental contamination from farm, fecal, dirty water inoculation or other equivalent (if indicated, primary wound closure/coverage is allowed) vii. IIIA Fractures where the skin could be closed after extensive muscle or bone removal (if indicated, primary wound closure/coverage is allowed) viii. IIIA fractures with bone loss resulting in a circumferential gap of 1 cm after debridement (if indicated, primary wound closure/coverage is allowed) ix. Fractures where fasciotomies were performed for impending or diagnosed compartment syndromes (regardless of the initial open or closed classification of the fracture x. Traumatic "zone-of-injury" trans-tibial amputations requiring DPC, and/or flap coverage

• Ages 18 - 64 years inclusive
• Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
• Patients may have a traumatic brain injury.
• Patients may have other fractures including spine, upper extremity fractures, contralateral lower extremity injuries, ipsilateral pelvis, hip, femur, or foot injuries.
• Patients may be treated initially at an outside institution prior to transferring to the study institution, as long as the definitive wound closure/coverage was not performed prior to entrance into the study.
• 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.
• Patients may have co-existing non-tibial or hindfoot infections, with or without antibiotic treatment.
• Patients may be definitively stabilized using any method (nail, plate, ex fix, or cast).
• Patients may have fasciotomy.

Exclusion criteria

• Patient speaks neither English or Spanish
• Patient in current therapy for a wound, implant or fracture site infection related to the study site.
• Patient is pregnant, potentially pregnant, or lactating.
• Patient likely to have difficulty maintaining follow-up, including:

• Diagnosis of a severe psychiatric condition
• Intellectually challenged without adequate family support
• Resides outside of the hospital's catchment area, unless willing to follow-up by phone or telemedicine
• Planning to follow-up at another medical center, unless willing to follow-up by phone or telemedicine
• Being a prisoner
• Not having a means of contact (address, cell phone, home phone, e-mail)