FRI should be suspected in cases of poor bone healing, poor soft tissue coverage, sinus formation, or persistent pain. The diagnosis of FRI can be challenging in certain situations without clear signs of infection.There are a few things to keep in mind before assessing a patient with suspected FRI:

Firstly, patients with signs of systemic sepsis are an emergency and require an immediate assessment and urgent sepsis management. This condition is relatively rare in FRI patients, especially when there are discharging wounds.

Secondly, the differentiation between early and late or chronic FRI is important to make from the start. For suspected early FRI (within 6 weeks after the injury or the surgery), early intervention is more important to ensure good outcomes. In chronic FRI, treatment can be scheduled and there is time to optimize the patient condition and to refer to a dedicated multidisciplinary team in an expert centre, even when this takes a few weeks time.

The diagnosis of FRI is made when a patients’ condition meets certain criteria, as proposed and published by an international expert group. The criteria have been subdivided into pre-operative criteria and post-operative criteria. In both situations confirmatory signs or suggestive criteria have been defined.

The following flowchart outlines the diagnostic process of FRIs.

Pre-operative criteria

FRI diagnosis is easy if there is pus draining from a wound or sinus from the fracture side (with or without an exposed fracture or implant). In low-resources settings this is the easiest and the most common presentation of FRI.

Additional suggestive preoperative criteria:

• Local redness and fever
• New onset joint effusion
• Persistent, increasing or new-onset wound drainage

If only suggestive criteria are found, we recommended diagnostic sampling [link to subsection], if resources to get reliable cultures are available. Avoid sinus tract or wound swabs; instead, take intra-operative samples.

In situations where resources are limited, consider referring the patient to a better equipped center, if feasible. If not, try to do the best you can with the resources available, but be aware of the risks: do no further harm.

Post-operative criteria (after sampling in the OR)

Post-operatively, diagnostic criteria are based on the results of the deep cultures that are taken surgically in a sterile environment in the operating theatre.

Diagnostic sampling is a crucial step in the treatment of FRI. It is essential that it is performed correctly as it provides the only opportunity to obtain uncontaminated culture samples. It is the foundation of the antibiotic regimen that follows.

How to perform accurate diagnostic sampling

Stop antibiotics 2 weeks before sampling if the patient is stable, especially in chronic FRI.

• “No Touch Technique” – While it is tempting to feel the consistency of the tissues during sampling, this is not the time. Only touch tissues with instruments and avoid cross contamination by touching. This may seem irrelevant as everything seems to be infected, but it can provide the microbiologist with essential information.
• Take five samples for culture and sensitivity and label them clearly – This may seem excessive, but it provides redundancy while allowing for a double check of the causative pathogen. If fungal culture is required, discuss this with the lab.
• Use five dedicated sets of clean instruments – Avoid cross contamination of specimens at all costs. Consider using disposable scalpels and forceps if resources are limited.
• If possible, send implants for sonication – This technique aims to break the biofilm of the implant with ultrasonic waves. The explanted implant is in a box with fluid; after sonication, this fluid is cultured.
• What to sample:
  • Abscess wall/pus
  • Tissue around implant/interface tissue (between plate and bone)
  • Dead bone
  • Loose implants
  • Non-union tissue/callus
  • Take deep samples: NEVER skin or sinus tract
  • Possible: Joint fluid, synovial biopsy and joint capsule; bodily fluids may be collected in blood culture bottles
  • In patients unable to undergo surgery, only fluid aspiration may be used.

The diagnosis of FRI is confirmed by identifying two or more indistinguishable microorganisms in the intra-operative samples. The diagnostic accuracy of sampling is 84% when 3 samples are taken, increasing to 97% for 5 samples taken in high-income setting. Increasing the number of samples therefore is the best way of ensureing a diagnosis.

KEEP YOUR HANDS CLEAN - Clean hands and gloves are a sign of proper sampling, as this reduces the chance of cross contamination.

Additional value of histology: In patients that do not have clinical confirmative criteria of FRI, two or more bone/soft tissue samples are recommended. In resource-limited settings, a single sample may be acceptable. The presence of micro-organisms or more than 5 polymorphonuclair neutrophils per field is confirmative for FRI.

FRI diagnostics: Imaging and lab tests

Additional investigative modalities are available to search for other suggestive criteria when diagnosing FRI.

Clinical chemistry: CRP, WBC, ESR

Blood tests are of limited diagnostic value. While elevated levels of CRP, WBC and ESR are suggestive of FRI, normal values do not exclude an infection. Additional blood tests are important to check general health and identify treatable problems (anaemia, vitamin D deficiency, diabetes, HIV) that help with host optimization.

Plain X-rays

X-rays should be the first imaging you perform. They can show bone lysis, implant loosening, sequestration, non-union or malunion, or when taken over a span of time show changes in the fracture site that can aid in diagnosis. However, there is no evidence of the diagnostic reliability of a plain radiograph. More advanced imaging is recommended for specific indications, if available, but is of relatively limited value, even in settings where these resources are available.

CT

Shows fracture configuration more clearly and can be used in surgical planning for fracture management. Relatively low diagnostic performance for FRI (sensitivity 47% and specificity 60%) but can be useful to detect abscesses and sequesters.

MRI

Very useful in mapping the extent of tissue inflammation. Cannot distinguish between inflammation of normally healing bones and tissue or inflammation due to infection. The sensitivity is 82–100%, specificity 43–60%. MRI may not be appropriate when a patient has metal implants

FDG-PET

Useful scan for diagnosing FRI, specifically if presentation is more than one month after surgery. Sensitivity is 65–94%, specificity 76–100%.

3-phase bone scan

High sensitivity (89–100%), low specificity (0–10%). Not recommended in the workup of FRI.

WBC scintigraphy

The sensitivity 79–100% and sensitivity 89–97%. A major advantage of WBC scintigraphy is that its accuracy is not influenced by recent surgery. This technique is laborious, constly and time consuming and it is less accurate in the axial skeleton.

Ultrasonography

While this modality of imaging may be used for fracture diagnosis, in the case of FRI its use is limited. However, it may identify massive abscesses and provides the possibility of USS guided aspiration of fluid collections to culture. In patients who are unfit for surgery, this can allow targeted antibiotic treatment.