A fracture-related infection (FRI) is a serious complication of a fracture. They can occur in open or closed fractures, particularly in fractures that were treated with open reduction and internal fixation.

^{Presentation of Fracture-Related Infection (FRI) across Mild, Moderate, and Severe Stages}

Around 1.8 Around 1.8 million FRIs occur globally each year. Rates are expected to rise due to more road accidents, better fracture care, and increasing rates of diseases like diabetes. FRI accounts for a high morbidity and mortality rate and can have a substantial socioeconomic impact on patients and those around them. FRI requires timely diagnosis and appropriate management. An unsuccessful or ineffective treated FRI may result in permanent functional loss or even amputation in otherwise healthy patients.

The management of FRI is resource intensive and a succesful treatment plan is adapted in the available resources. Governments, clinicians, industries and NGOs should collaborate to improve availability of these resources, while simultaneously training clinicians in orthopedic and plastic surgical skills to create multidiciplinary units specialized in treating FRI. More research is needed to improve evidence-based care in low-resource settings.

Definition of an FRI

An infection of the bone or osteosynthesis material secondary to a fracture is defined  as a fracture-related infection (FRI). The criteria for diagnosing FRI were defined in 2018 after a consensus meeting with input from 2,000 surgeons. For the criteria we refer to the chapter: 'How to diagnose FRI'.

In the past, different terms have been used in the literature, including a fracture with osteomyelitis or osteitis. However, today it is recommended to use these terms to describe infections in bone without a fracture. These bone infections without a fracture form a heterogeneous group often related to another medical condition, like diabetes mellitus, vascular insufficiency, dissemination of hematogenous infection, trauma without a fracture or sickle cell disease, among others.

FRI in resource-limited settings

Fracture-related infection (FRI) puts a heavy burden on health systems, especially in low-resource settings. Evidence and guidelines for FRI come from high-income countries. They may not fit low-resource settings because of differences in for example access to surgery, implants, imaging, microbiology, patient health, and funding.

In resource-limited settings, an FRI is often already present when the patient comes to the hospital for the first time with an open fracture. This is because patients in these settings are more likely to have delays in seeking or receiving hospital care.

(Hematogenous) osteomyelitis leading to a fracture is also classified as an FRI. This condition is uncommon in high-income settings, but it can be seen more often in LMICs settings, mainly in children. It is often related to poor nutritional status and/or sickle cell disease. Proper recognition of this specific condition is important as it will affect treatment choices and prognosis. 

Pathophysiology of FRI

FRI is caused by the introduction of a pathogen to the fracture site. This can be through:

• Introduction during injury, i.e. penetrating trauma or an open fracture.
• Introduction during treatment, i.e. intraoperatively.

Introduction during injury

How - Direct introduction of micro-organisms from the environment.

Microorganisms involved - Mainly bacteria (predominantly skin flora and environmental bacteria), sometimes fungi.

What happens - Tissue devitalization (death of soft tissue and bone due to trauma) creates a good medium for bacterial growth. Hematoma and dead bone fragments act as nutrients and surfaces for bacterial colonization, while simultaniously local immune defenses are impaired due to vascular damage. Abscess formation can develop as neutrophils respond, leading to pus collection and further necrosis.

Impact - The risk of fracture-related infection increases with the severity of soft tissue damage and can be up to more than 40% in open fractures with extensive soft tissue injury.

Introduction during treatment

How - Infection can occur intraoperatively during fracture fixation or debridement.

Microorganisms involved - S. aureus is an important organism associated with infection after surgery because of its virulence factors.

What happens - Common contamination sources include non-sterile instruments, implants, inadequate skin preparation, or airborne particles in the operating room. Additionally, orthopedic materials (plates, screws, nails) facilitate bacterial adhesion, which begins within minutes. If not cleared, bacteria form a biofilm, a protective matrix that resists microorganisms from the immune system and antibiotics.

Impact - Even minimal contamination can result in chronic infection due to the biofilm.

Postoperative or late-onset infection

How - Infections can develop later due to poor wound healing, delayed soft tissue coverage, or biofilm formation in dead spaces or on fixation materials.

Microorganisms involved - Bacteria in biofilms may be few in number or slow-growing, which makes detection and treatment difficult. However, time since injury does not directly influence the type of causative microorganism.

What happens - Biofilms commonly form on necrotic bone and implants, and resist treatment through blocking immune cells, limiting antibiotic penetration, and resisting mechanical debridement/removal. Their microbial composition varies with oxygen and nutrient levels, complicating eradication.