Diagnostic Challenges in Bone and Joint Infections: Lessons learned from international collaborations

Abstract

Fracture-related infections (FRI) and periprosthetic joint infections (PJI) are serious complications in trauma and orthopedic surgery, resulting in high morbidity, loss of function, implant failure, decreased patient-reported outcome measures (PROMs) and even amputation. This thesis focuses on improving the diagnosis and treatment of these diseases by analyzing current strategies and providing insight into patient characteristics.

In Chapter 1, the background and burden of the two trauma and orthopaedic infection entities FRI and PJI are introduced, their definitions and treatments are discussed, and an outline of this thesis is presented.

Part I focuses on FRI. Chapter 2 and 3 focus on the three commonly used serum inflammation markers C-reactive protein (CRP), white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) for FRI in a large retrospective cohort study and systematic review and meta-analysis. The markers seem insufficiently accurate to confirm or rule out the presence of FRI and should solely be used as suggestive criteria in its diagnosis. Chapter 4 reviews the diagnostic accuracy of nuclear imaging using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). 18F-FDG PET/CT shows 0.83 accuracy, however demonstrates an increase in false negative results within one month postoperatively. Chapter 5 provides an overview of the outcomes and risk factors for recurrence of early FRI after debridement, antibiotics and implant-retention (DAIR). The recurrence rate was 13% at 12 months and independent predictors were use of an intramedullary nail during index operation, additional surgical procedures, and a decreased injury severity score (ISS).

Part II focuses on PJI. Chapter 6 evaluates the utility of commonly used serum markers CRP and ESR and synovial markers WBC count and percentage polymorphonuclear neutrophils (PMN%) for PJI in patients presenting with periprosthetic fractures. All markers demonstrated less accurate than in PJI alone. Clinicians should use higher cut-off values and a combination of all markers. Chapter 7 assesses the treatment outcomes one- and two-stage revision for chronic culture-negative PJI. One-stage revision shows comparable results to two-stage (re-infection 16.7% vs. 20.0% (p=0.69)), suggesting culture negativity may not be a contraindication for these patients. In chapter 8, revision total hip and knee arthroplasty for infected internal fixation of peri-articular fractures shows higher recurrence rates than for aseptic revision (35.0% vs. 11.3% (p=0.005), with more than one third due to mixed and resistant pathogens. Chapter 9 presents the outcomes and risk factors for re-revision surgery following failure of revision for periprosthetic fracture of the hip and knee. PJI of the hip and knee is the most common complication after re-revision (7.9% resp. 17.7%) and third revision surgery (10.0% resp. 17.4%). Factors significantly contributing to an increased risk of re-revision included revision with plate fixation and revision with combined internal fixation.

The dissertation concludes with a discussion in Chapter 10, in which the value of diagnostic and treatment strategies for FRI and PJI is discussed. Furthermore, lessons that were learned while conducting the research in this thesis are described. In addition, recommendations are made for future research to improve care for trauma and orthopedic patients.