The value of current diagnostic techniques in the diagnosis of fracture-related infections: Serum markers, histology, and cultures

•Routine serum inflammatory markers CRP, ESR, and WBC have limited diagnostic value in preoperative diagnosis of FRI.•Histology is characterized by high specificity, with the best sensitivity observed for the quantitative method.•Culture exhibits higher sensitivity than histology, whether qualitative or quantitative.•Microbiology can be improved by increasing sample number, implementing long-term culture, and adjunctive implant sonication. Although fracture-related infection (FRI) is a serious complication following bone fractures, a comprehensive definition and diagnostic criteria have only emerged in recent years. According to this consensus definition, the diagnosis of FRI is based on preoperative and intraoperative suggestive or confirmatory criteria. Serum markers, histology, and microbiological cultures are considered to play a crucial role in the FRI diagnostic pathway. However, at the time of publication of the FRI consensus definition in 2018 and its update in 2020, limited data was available on the accuracy of these diagnostic methods. This review aims to provide an overview of recent publications and discuss whether new evidence has been obtained regarding the value of these current diagnostic techniques. Meanwhile, several studies have confirmed the limited prognostic value of C-reactive protein, erythrocyte sedimentation ratio, and white blood cell count. Other serologic markers for preoperative diagnosis of FRI with promising diagnostic performance are d-dimer, plasma fibrinogen, platelet count to mean platelet volume ratio, and a risk prediction model that includes soft tissue injury type and fracture complexity in addition to blood markers. However, their true diagnostic value in daily clinical practice needs to be investigated in further studies. Data on histology in FRI diagnosis is still limited, but its potential as a confirmatory criterion seems to lie in its high specificity. Recent studies indicate that tissue culture exhibits moderate sensitivity and high specificity, with sensitivity improvements achieved by sampling of five specimens and long-term culture. Implant sonication also appears to enhance the sensitivity of culture and the detection rate of polymicrobial infections. In conclusion, the true value of diagnostic techniques is difficult to assess, in part because it is measured against a gold standard that is itself imperfect and still evolving, but also because of methodological differences in sample processing or the use o