High diagnostic accuracy of white blood cell scintigraphy for fracture related infections: Results of a large retrospective single-center study

Abstract

Introduction

White blood cell (WBC) scintigraphy for diagnosing fracture-related infections (FRIs) has only been investigated in small patient series. Aims of this study were (1) to establish the accuracy of WBC scintigraphy for diagnosing FRIs, and (2) to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its accuracy.

Patients and methods

192 consecutive WBC scintigraphies with ^99mTc-HMPAO-labelled autologous leucocytes performed for suspected peripheral FRI were included. The golden standard was based on the outcome of microbiological investigation in case of surgery, or − when these were not available – on clinical follow-up of at least six months. The discriminative ability of the imaging modalities was quantified by several measures of diagnostic accuracy. A multivariable logistic regression analysis was performed to identify predictive variables of a false-positive or false-negative WBC scintigraphy test result.

Results

WBC scintigraphy had a sensitivity of 0.79, a specificity of 0.97, a positive predicting value of 0.91, a negative predicting value of 0.93 and a diagnostic accuracy of 0.92 for detecting an FRI in the peripheral skeleton. The duration of the interval between surgery and the WBC scintigraphy did not influence its diagnostic accuracy; neither did concomitant use of antibiotics or NSAIDs. There were 11 patients with a false-negative (FN) WBC scintigraphy, the majority of these patients (n = 9, 82%) suffered from an infected nonunion. Four patients had a false-positive (FP) WBC scintigraphy.

Conclusions

WBC scintigraphy showed a high diagnostic accuracy (0.92) for detecting FRIs in the peripheral skeleton. Duration of the time interval between surgery for the initial injury and the WBC did not influence the results which indicate that WBC scintigraphy is accurate shortly after surgery.

Introduction

Postoperative infection is one of the most common and yet also most severe complications associated with the surgical fixation of fractures. It results in increased morbidity, higher medical costs and prolonged hospital admission times [[1], [2]]. Despite new and promising methods to prevent and treat these infections, the key to successful management is to establish an early and correct diagnosis. A distinction used to be made between early and late infections. However, classifications are rather arbitrary and there is no scientific evidence that the timing of the onset of the infection has any effect on the diagnostic tests or the treatment outcome. As a result, new definitions are being developed. In a recent consensus meeting supported by the Association for the Study of Internal Fixation (Arbeitsgemeinschaft für Osteosynthesefragen, AO), it was agreed to refer to the complete spectrum of infections following surgical fixation of a closed or open fracture as “fracture-related infection” (FRI) when no further detailed information is available on the degree of bone involvement. Also, clear definition criteria now finally exist [3]. Many factors (both patient-related and doctor- or health institution-related) play a role in the clinical decision-making process for diagnosing FRI [[4], [5]]. Usually it is not early FRIs which pose a diagnostic challenge. Clinical signs of early infections are clear and tend to be easily recognizable, requiring limited or no additional diagnostic imaging. From a diagnostic perspective it is the established form of FRI which can be difficult to diagnose, and advanced medical imaging can be indispensable. However, most studies that investigate the accuracy of these advanced imaging modalities are aimed at hematogenous osteomyelitis and prosthetic joint infections (PJIs), or are conducted in an inhomogeneous orthopedic population with infections of different etiology [[6], [7], [8]]. FRIs are a different entity than PJIs because fracture fixation implants are in situ, which often allows micro-motion of the surrounding bone in contrast to an articulating but otherwise rigid prosthesis. There may also be confounding factors present such as a recent fracture with regenerating bone, soft-tissue disruption and/or other concomitant injuries. In many countries white blood cell (WBC) scintigraphy is a commonly utilized imaging modality for orthopedic infections, including FRI [[9], [10]]. However, although labeling and interpretation guidelines for WBC scintigraphy are now set by the European Association of Nuclear Medicine (EANM) [11], evidence of its accuracy in FRIs is limited in the literature [12]. There is also uncertainty regarding the minimum time interval required between surgery and WBC scintigraphy in order to minimize postoperative artifacts (and therefore false-positive results). As a FRI is a surgical complication it is important to know how previous surgery influences the outcome of any diagnostic test.

To resolve these questions, the two aims of this study were:

• to establish the accuracy of WBC scintigraphy for diagnosing FRI in a large and homogeneous patient group.

• to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its diagnostic accuracy.