Accuracy of Tissue and Sonication Fluid Sampling for the Diagnosis of Fracture-Related Infection: A Systematic Review and Critical Appraisal

Onsea, Jolien; Depypere, Maarten; Govaert, Geertje A M; Kuehl, Richard; Vandendriessche, Thomas; Morgenstern, Mario; McNally, Martin; Trampuž, Andrej; Metsemakers, Willem‐Jan

doi:10.7150/jbji.27840

Cited by 40 publications

(45 citation statements)

References 30 publications

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“…All of the patients had a follow-up for at least one year, and none of them had a clinical relapse of the infection. This is in line with other studies that have reported positive cultures in 28.7% of cases with presumptive aseptic nonunions [ 19 ]. Amorosa et al [ 19 ] reported that 7 patients of the total 15 with positive cultures underwent a secondary operation.…”

Section: Discussionsupporting

confidence: 93%

Can CRP Levels Predict Infection in Presumptive Aseptic Long Bone Non-Unions? A Prospective Cohort Study

Tosounidis

Holton

Giannoudis

et al. 2021

JCM

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Nonunion remains a major complication of the management of long bone fractures. The primary aim of the present study was to investigate whether raised levels of C-reactive protein (CRP) and white blood cell count (WBC), in the absence of clinical signs, are correlated with positive intraoperative tissue cultures in presumptive aseptic long-bone nonunions. Infection was classified as positive if any significant growth of microorganisms was observed from bone/tissue samples sent from the theater at the time of revision surgery. Preoperatively all patients were investigated with full blood count, white blood count differential as well as C-reactive protein (CRP). A total of 105 consecutive patients (59 males) were included in the study, with an average age of 46.76 years (range 16–92 years) at the time of nonunion diagnosis. The vast majority were femoral (56) and tibial (37) nonunions. The median time from the index surgical procedure to the time of nonunion diagnosis was 10 months (range 9 months to 10 years). Positive cultures revealed a mixed growth of microorganisms, with coagulase-negative Staphylococcus (56.4%) being the most prevalent microorganism, followed by Staphylococcusaureus (20.5%). Pseudomonas, Methicillin-Resistant Staphylococcus aureus (MRSA), coliforms and micrococcus were present in the remainder of the cases (23.1%). Overall, the risk of infection with normal CRP levels (<10 mg/L) was 21/80 = 0.26. Elevated CRP levels (≥10 mg/L) increased the risk of infection to 0.72. The relative risk given a positive CRP test was RR = 0.72/0.26 = 2.74. Overall, the WBC count was found to be an unreliable marker to predict infection. Solid union was achieved in all cases after an average of 6.5 months (3–24 months) from revision surgery. In patients with presumed aseptic long bone nonunion and normal CRP levels, the risk of underlying low-grade indolent infection can be as high as 26%. Patients should be made aware of this finding, which can complicate their treatment course and outcomes.

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Section: Discussionsupporting

confidence: 93%

Can CRP Levels Predict Infection in Presumptive Aseptic Long Bone Non-Unions? A Prospective Cohort Study

Tosounidis

Holton

Giannoudis

et al. 2021

JCM

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“… 32 Prior studies reported sonication fluid sensitivity for FRI at between 65% and 95%, with specificity between 50% and 97%. 33 Sonication should be used together with deep tissue sampling for optimum diagnostic accuracy. 28 , 32 …”

Section: Microbiological Diagnosis Of Frimentioning

confidence: 99%

“… 8 The reason for this was the lack of clear scientific evidence and, more specifically, agreement on a cut-off value above which FRI can be reliably diagnosed. 8 , 33 …”

Section: Histopathologymentioning

confidence: 99%

Definition and diagnosis of fracture-related infection

et al. 2020

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Fracture-related infection (FRI) is common and often diagnosed late. Accurate diagnosis is the beginning of effective treatment. Diagnosis can be difficult, particularly when there are no outward signs of infection. The new FRI definition, together with clear protocols for nuclear imaging, microbiological culture and histological analysis, should allow much better study design and a clearer understanding of infected fractures. In recent years, there has been a new focus on defining FRI and avoiding non-specific, poorly targeted treatment. Previous studies on FRI have often failed to define infection precisely and so are of limited value. This review highlights the essential principles of making the diagnosis and how clinical signs, serum tests, imaging, microbiology, molecular biology and histology all contribute to the diagnostic pathway. Cite this article: EFORT Open Rev 2020;5:614-619. DOI: 10.1302/2058-5241.5.190072

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“…However, the exact conditions and mechanisms underlying the VNBC concept remain to be fully understood, but do represent a possible risk in ODRI studies. To maximize chances of accurate culture results, adopting clinical methods towards improved isolation and culture of biopsies should also be considered, that is, sonication of biopsies and associated hardware components or the use of known biofilm‐dispersing agents during sample processing …”

Section: Bacteriological Aspects Of Odri Studiesmentioning

confidence: 99%

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

Moriarty

Harris

Mooney

et al. 2019

Journal Orthopaedic Research

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Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drugdevice combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience-driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation.

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Accuracy of Tissue and Sonication Fluid Sampling for the Diagnosis of Fracture-Related Infection: A Systematic Review and Critical Appraisal

Cited by 40 publications

References 30 publications

Can CRP Levels Predict Infection in Presumptive Aseptic Long Bone Non-Unions? A Prospective Cohort Study

Can CRP Levels Predict Infection in Presumptive Aseptic Long Bone Non-Unions? A Prospective Cohort Study

Definition and diagnosis of fracture-related infection

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

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