The study focuses on the serious problem of infections and wound-healing issues that can happen after high-energy bone fractures. These complications are common and can affect between 10% and 60% of patients, especially those with severe injuries. When a fracture is repaired with surgery and an infection develops afterward, patients often face long recovery times, more pain, and sometimes multiple surgeries. In the worst cases, the infection can lead to permanent disability or even amputation. The current standard test used in hospitals, called a culture, often misses certain bacteria, which can make treatment less effective. Because of this, the study aims to find out whether adding a newer test called Next Generation Sequencing (NGS) can help doctors identify infections more accurately and improve patient outcomes.

The main goal of the study is to see whether using NGS along with standard hospital cultures reduces the number of treatment failures compared to using standard cultures alone. Treatment failure means the infection does not get better and the patient must return to the operating room. The study also wants to learn whether NGS helps doctors make better antibiotic choices and avoid unnecessary or ineffective treatments. Another goal is to understand which NGS results are most helpful when doctors decide to change a patient's antibiotics. By learning this, researchers hope to create a model that explains how NGS information influences treatment decisions.

To join the study, patients must be between 18 and 84 years old and have a deep infection after a fracture was repaired with internal fixation, such as plates, screws, or rods. Patients must also meet infection criteria from either the Fracture-Related Infection (FRI) guidelines or the CDC's infection criteria. A total of 250 patients will be randomly placed into one of two groups: one group will receive treatment guided by both NGS and standard cultures, while the other group will receive treatment based only on standard cultures. Researchers will then compare how often treatment fails in each group.

Treatment failure includes several possible outcomes. The most important is an unplanned return to the operating room because the infection did not improve. Other types of failure include new superficial infections that do not require surgery, bones that fail to heal properly (called nonunion), amputation, and complications caused by antibiotics. Patients will return for follow-up visits at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after joining the study so researchers can track the patient's progress and monitor for any problems.

Right now, the failure rate for treating these infections using standard hospital cultures is about 30%, which is considered unacceptably high. The researchers believe that adding NGS will help lower this number because NGS can detect more types of bacteria, including ones that are hard to grow in a lab. With better information, doctors can choose antibiotics that are more likely to work the first time, which may reduce the need for additional surgeries and improve healing. This could be especially important for military service members, who often suffer high-energy injuries and face a greater risk of long-term complications if treatment fails.

NGS is already available, covered by Medicare, and fast enough to be useful in real-time medical decisions. If this study shows that NGS improves treatment outcomes, hospitals could begin using it widely and quickly. The researchers hope that this approach will lead to fewer infections, better antibiotic use, faster recovery, and improved long-term function for patients.

Inclusion Criteria:

• Age 18-84 years
• History of extremity fracture proximal to the metatarsals and carpal bones treated with any type of internal fixation. Note that both healed and unhealed fractures are eligible.
• Deep infection requiring surgery after fracture fixation as determined by either of the following:

FRI confirmatory criteria CDC criteria (without the timeframe). This includes the possibility of culture negative infection but determined to be infection by treatment team.

• Plan for treatment includes antibiotic therapy prescribed by Infectious Disease provider(s), regardless of SOCHB culture or NGS results.

Exclusion Criteria:

• Spine fractures
• High risk of amputation based on the initial managing physician opinion
• Incarcerated/institutionalized
• Patient is too sick to have surgery, i.e., medical co-morbidities which preclude treatment with a general anesthetic
• Prior history of chronic infection at the surgical site
• Pathological fractures from a neoplastic process
• History of Paget's Disease
• Unavailable for the planned 12 months of follow-up (e.g., planned follow-up at a location other than one of the study sites)
• Extremity fracture occurred more than 2 years prior to the hospital admission for the presenting infection

NGS results withheld from care team in one arm