What fracture is the most susceptible to infection?

INTRODUCTION

Fracture-related infection (FRI) is a severe complication following os injury and can pose a diagnostic claiming. There is a spectrum of clinical presentations of Fri and differentiating them from noninfected causes can be difficult. In the early on postoperative menstruum, classical clinical symptoms of infection, such as pain, redness, warmth, or swelling, overlap with features of normal fracture healing. Later, more subtle clinical presentations such as fracture nonunion or persistent pain can be owing to both infective and noninfective weather condition. The complexity and variety of Friday may have hindered the establishment of compatible diagnostic criteria. In addition, the lack of diagnostic guidance has led to uncertainty in the direction and handling of these patients.

These challenges highlight a need for standardized interdisciplinary diagnostic and treatment approaches. In dissimilarity to periprosthetic articulation infection (PJI), protocols tailored to infection in patients later musculoskeletal trauma are deficient. Therefore, many of the surgical and medical treatment concepts applied to Fri accept been adopted from PJI treatment algorithms. Both conditions have a multistage process of diagnosis in common based on various diagnostic pillars. However, important differences exist between fractures and arthroplasties. Therefore, it is striking that there is little scientific evidence for the predictive value of diagnostic investigations specifically focusing on FRI.

The lack of a uniform definition for FRI may as well have contributed to the scarcity of comparable data on diagnostic strategies. This shortcoming was confirmed by a recent systematic review, showing that but a minority of randomized controlled trials in fracture care utilise any kind of standardized definition of FRI. ¹ The absence of a universally accepted definition of FRI is similar to the state of affairs for PJI many years agone. ² The development of uniform criteria for the diagnosis of PJI has led to an improvement in the diagnostic process of PJI afterwards hip and knee joint arthroplasty. ^3,4 There is now growing awareness amid orthopaedic and trauma surgeons that FRI is a unique entity and that a definition of FRI is required. ⁵ The need for a uniform definition for Friday is closely related to the need for a uniform diagnostic pathway. In 2015, a survey of practitioners involved in the care of patients with Fri showed that at that place was no consensus on the optimal diagnosis of infection. ^six

For these reasons, the AO Foundation and the European Bone and Articulation Infection Club (EBJIS) recently proposed a consensus definition for Fri to standardize the diagnostic criteria and improve the quality of patient intendance and applicability of future studies regarding this condition. ⁷

The aim of this article is to summarize the available evidence and to provide recommendations for the diagnosis of Fri. For this purpose, first the diagnostic criteria included in the recently published FRI consensus definition will be discussed together with a proposal for an update regarding nuclear imaging modalities and histopathological exam. This update is based on a 2nd consensus meeting including not simply the AO Foundation and the EBJIS simply also the Orthopaedic Trauma Association and the PRO-Implant Foundation. Furthermore, recommendations on microbiology specimen sampling techniques and laboratory operating procedures relevant to Fri will be provided.

DEFINITION

In 2018, the aforementioned consensus definition for FRI was published. ⁷ The development process was comparable to the ane used for the new definition on PJI. ⁸ An international group of experts was involved, representing the AO Foundation and EBJIS as well as prominent orthopaedic trauma hospitals and academic centers with specific interest and clinical experience in Friday. Acknowledging the multidisciplinary nature of FRI, physicians from different specialties were included. Later on review of the literature and video conferences, a face up-to-confront consensus meeting was held and a concluding agreement on the definition of Friday was reached. It was accepted that some features of Fri can be regarded as definitive proof of infection and should exist given more weight in the definition. Other less specific features may propose an infection just may also be nowadays in patients without infection. This resulted in a prepare of confirmatory criteria (infection definitely present) and suggestive criteria (infection possibly nowadays). An updated diagnostic flowchart as proposed past the FRI consensus group will be provided at the end of this article.

DIAGNOSTIC CRITERIA

The diagnosis of Fri is a multistage process based on various important diagnostic pillars. Authors of the consensus definition on FRI concluded that there is a scarcity of solid bear witness on which such a definition could be based. ⁷ Thus, many of the included criteria were based on expert stance. In the following sections, the diagnostic possibilities for patients with FRI will be described and evaluated based on electric current evidence.

Clinical Criteria

The clinical features used to define FRI were analyzed in 2 recent systematic reviews. In the first review, the authors identified definitions used in the scientific literature to draw infective complications after internal fixation of fractures. ^ane The second review provided an overview of the available diagnostic criteria, classifications, handling protocols, and patient-related outcome measurements for surgically treated Fri patients between 1990 and 2017. ⁹ Both reviews describe a large variety of clinical signs, with the only ii undisputable definitive criteria being purulent drainage and wound dehiscence/breakdown. This corresponded to the conclusion of the consensus meeting on Fri: the presence of a fistula, sinus, or wound breakdown (with advice to the bone or implant) and/or purulent drainage from the wound or presence of pus during surgery are regarded as pathognomonic and are confirmatory clinical signs for the diagnosis of FRI. ⁷ To our knowledge, no studies have reported on the predictive value of systemic or local clinical signs of infection for Fri. However, it was accepted by the consensus group that the presence of FRI can be indicated by clinical signs comprising local redness, swelling, increased local temperature, fever (≥38.3°C), or persistent, increasing, or new-onset wound drainage across the first few days postoperatively. Therefore, these features were regarded as suggestive clinical signs for Fri. It is of import to realize that these suggestive criteria are not pathognomonic and therefore should prompt the treating surgeon or physician to farther investigate the possibility of an Fri.

Serum Inflammatory Markers

The most unremarkably used serum inflammation markers in orthopaedic surgery are leukocyte count (LC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).

Leukocytes, and more than specifically neutrophils, are the kickoff innate allowed cells that are rapidly recruited from the bloodstream to sites of infection and act as major phagocytes. The number of leucocytes and neutrophils can be measured in the blood, and therefore, they are ofttimes used as a surveillance tool for (postoperative) infection. Although an increment to a higher place normal parameters tin can be an indication of infection, their number will as well increase in the presence of other causes of cell damage, such as trauma, surgery, sterile inflammation, systemic inflammatory diseases, and malignancies. ^ten,11 In spinal surgery, it is reported that maximum values of LC are seen on days i to 3 postoperatively and turn down to normal values between days iv and six. ¹²

Levels of CRP are known to increase in response to various stimuli, such as infection, tissue impairment, acute coronary syndrome, and allergies. ¹³ The functions of CRP include recognizing microbial pathogens, activating the complement pathway, and leucocyte phagocytosis. ¹⁴ In fracture patients, CRP levels increase to a maximum on the second day and and so return to normal later 2 weeks. ¹⁵

Other acute phase proteins (particularly fibrinogen, haptoglobin, and ceruloplasmin) and immunoglobulins (mainly IgM) cause a decrease in the negative surface charge of erythrocytes with subsequently increased agglutination and rouleaux formation (stacks of erythrocytes). Therefore,infection results in an increase in the relative weight of erythrocytes expressed by elevated ESR. Values of ESR meridian at days 7–11 postoperatively post-obit spinal instrumentation and subtract gradually until calendar week 6. ^sixteen

Summit of the 3 inflammatory markers (LC, CRP, and ESR) may be seen in trauma patients due to a systemic inflammatory response, postoperative tissue impairment, and surgical infections. ^11,17–21 In a recent systematic review, the diagnostic value of the serum inflammatory markers CRP, LC, and ESR in suspected chronic/late-onset FRI was assessed. ²² Of a total of 8280 articles that were identified, but 6 were included. CRP appeared to be the most useful serum inflammatory marker with a sensitivity ranging between 60.0% and 100% and specificity between 34.3% and 85.7% (cutoff values varied between 5.0 and 10.0 mg/50). Meta-assay of the pooled results showed limited diagnostic value of all 3 markers individually. For these reasons, the analyzed serum inflammatory markers (CRP, LC, and ESR) are insufficient to ostend or rule out the presence of chronic/late-onset FRI. Another issue that complicated the analysis of the bachelor data was that different measuring devices, laboratory protocols, and/or thresholds were used.

Caution is warranted when interpreting the results of serum inflammatory markers in daily clinical practise, and they should be regarded only as suggestive criteria for Fri. ^seven Future research, using a clear definition of FRI and standardized laboratory protocols, will require appreciation of the continuous values of serum inflammatory markers and cess of their combined value in the diagnosis of FRI.

Medical Imaging

There are iii indications to request diagnostic imaging for Friday (1) to acquire more certainty regarding the presence or absence of FRI, (2) to visualize the anatomic details of the disease such as its extension, the presence of sequestra, cloacae, sinus tracts, and/or subcortical abscesses, for surgical planning, and (3) to establish the degree of fracture healing and implant stability. For these purposes, the clinician has a choice of several radiological and nuclear imaging techniques. Depending on local preference and availability, these techniques are near ordinarily conventional radiography, computed tomography (CT), magnetic imaging resonance (MRI), three-phase bone scan (BS), fluorodeoxyglucose positron emission tomography (FDG-PET), and white blood cell (WBC) scintigraphy. The diagnostic performance of these imaging modalities has increased at an nigh exponential charge per unit in recent years, which makes it difficult to compare historical data with current practice. Simply 1 study reviewed the recent literature (from 2000 to 2016) on imaging techniques, specifically for the diagnosis of FRI. ²³

Although no adept quality written report on the diagnostic value of conventional radiography in Friday exists, this modality is near always requested first when an infectious complication related to a fracture is suspected. ^six It is easily bachelor, cheap, quickly performed, and has a low radiation exposure. The radiograph provides baseline information regarding the position of the fracture and the integrity and stability of whatsoever orthopaedic implant. A CT browse can be performed if more than details are required and is better in revealing the presence of sequestra and bone cavities. Nonetheless, its disadvantage is the radiation exposure and the depression discriminatory capacity for FRI (sensitivity 47% and specificity 60%). ^23,24 Universally accepted suggestive signs of infection on conventional radiography and CT scan are implant loosening, bone lysis, failure of progression of bone healing (nonunion), sequestration, and periosteal bone formation. ^vii

MRI is very useful for the imaging of soft tissue pathology. It is besides very sensitive for detecting morphologic bony changes, which makes it particularly useful in mapping specific surgical details, such as the extent of bone and soft tissue involvement and presence of sequestra, cloacae, sinus tracts, and/or subcortical abscesses. However, it can be hard to distinguish between changes due to infection, inflammation, and normal tissue healing, and scattering from metal implants can obscure sure imaging details despite metal antiquity reduction techniques. The sensitivity and specificity of MRI for the detection of FRI are reported to be betwixt 82% and 100% and between 43% and 60%, respectively. ^23–25

Nuclear imaging of FRI mainly involves BS, WBC scintigraphy, and/or FDG-PET. ^6,26 An important addition in contempo times is the possibility of hybrid imaging (unmarried photon emission CT [SPECT]/CT, PET/CT, PET/MRI), which allows for better anatomic details. ²⁷ The sensitivity of BS is high (89%–100%), but its specificity is so low (0%–10%) that BS is not recommended in the workup of FRI. ^23,25,28,29 The sensitivity and specificity of WBC scintigraphy + SPECT for diagnosing FRI is reported to exist 79%–100% and 89%–97%, respectively. ^{23,thirty–32} A major advantage of WBC scintigraphy is that its accurateness is not influenced past recent surgery. ³² Still, this technique is laborious and fourth dimension consuming, ³⁰ and it is less accurate in the centric skeleton. ^26,33 FDG-PET is slightly less authentic compared with WBC scintigraphy but still suitable for diagnosing Friday. This technique is based on the consumption of glucose every bit an free energy source by activated leukocytes, monocytes, lymphocytes, macrophages, and giant cells in infectious diseases. The major reward of PET above SPECT is a higher spatial resolution and the fact that quantification possibilities are meliorate with PET. Another advantage of FDG-PET is that it but requires one single browse in contrast to two imaging fourth dimension points for WBC scintigraphy (respectively, 3–4 and 20–24 hours subsequently reinjection of the labeled WBCs). ²⁶ FDG-PET should all the same not be used for detecting FRI within 1 month after surgery. ³⁴ The sensitivity and specificity of FDG-PET/CT for detecting Friday is between 65% and 94% and between 76% and 100%, respectively. ^23,34–38 Figures 1–3 show examples of MRI, FDG-PET/CT, and WBC scintigraphy + SPECT/CT findings in FRI, respectively.

FIGURE 1.:

Example of an x-ray (A) and T2-STIR MRI images (B coronal view, C sagittal view) performed in a patient with an infected proximal humerus fracture. The MRI demonstrated the extent of the infection with a skin defect, fluid/pus in the proximal humerus with surrounding edema, a sinus tract, and the involvement of the adjacent joint with possible involvement of the glenoid.

FIGURE two.:

A 57-year-erstwhile male patient sustained a combined left-sided neck-of-femur fracture, a patella fracture, and a Gustilo-Anderson type IIIB open intra-articular distal femur fracture with a segmental defect due to a motor vehicle accident (A: x-ray left femur, AP). The open reduction and internal fixation was complicated by a FRI for which an induced membrane (Masquelet) process was carried out combined with a 3-calendar month antibiotic treatment. Despite the fact that the patient was full–weight begetting and pain free, 2.5 years later, a fistula developed at his distal lateral left thigh. An x-ray (AP) of the left femur (B) showed that the implants were intact, the neck-of-femur fracture was healed and that there was bone germination on the medial side of the femoral fracture and over the lateral plate. At that place was no consolidation of the femoral defect. Preoperative workup included an FDG-PET/CT to assess the extent of the FRI. This browse demonstrated that the complete femur and all implants were involved in the infection and likewise visualized the trajectory of the soft tissue fistula. C–F, 18F-FDG PET/CT: (C) coronal FDG-PET image, (D) coronal fused FDG-PET/CT epitome, (E) sagittal fused FDG-PET/CT epitome, (F) transaxial FDG-PET/CT epitome with evidence of soft tissue fistula. (E) Preoperative clinical image with fistula (black pointer). (F) Intraoperative clinical paradigm: The bone overlying the lateral plate is removed, and the infection revealed. AP, Antero-posterior.

FIGURE iii.:

A fracture-related infection, caused by Enterobacter cloacae, in a 48-year-old man post-obit intramedullary nailing of the tibia. A, The patient presented with a draining fistula at the level of one of the distal locking screws, four months after placement of an intramedullary tibial nail. B, AP 10-ray of the right lower leg showing the intramedullary smash of the tibia and plate osteosynthesis of the fibula. C–D, Delayed (4 hours) and tardily (xx hours) static fourth dimension disuse corrected planar images (anterior view) of the lower leg, showing focally increased accumulation of WBCs at the level of the fistula extending toward the tibia. Note the increased tracer aggregating and increase in extension over time, indicating the presence of an infection. E, A fused SPECT-CT image of WBC scintigraphy (iv hours afterward tracer injection) showing focally increased accumulation of WBCs at the level of the fistula extending around the distal role of the smash and the distal locking screw.

In conclusion, every option for medical imaging in Fri has both advantages and disadvantages, and currently, there is a lack of show to suggest that one technique is superior to another. Therefore, currently, radiological signs tin can only be regarded as a suggestive benchmark for Fri. ⁷ Although nuclear imaging has a higher diagnostic accurateness, information technology is still not a conclusive examination to plant the presence of FRI; therefore, it tin can also only be included in the Fri Consensus Definition as a suggestive criterion of FRI.

Microbiology

The culture of distinct pathogens from at least 2 separate deep tissue/implant specimens is considered a confirmatory criterion of FRI. ⁷ In addition, the antibiotic susceptibility of the identified pathogens will guide the choice of antimicrobial treatment. Organisms causing chronic/late-onset infections around implants are often skin commensals and are therefore similar to those that can contaminate culture specimens during sampling or treatment in the microbiology department. Additionally, organisms can be present in small numbers or may be in tiresome growth mode in a biofilm. Because false-positive or false-negative results can lead to erroneous treatment decisions, sampling and culturing techniques should be meticulous.

Surgical sampling protocols have been previously validated for PJI ³⁹ and and then applied to Friday. ^xl,41 All preoperative antibiotics should, where possible, exist avoided for a menstruum of at least 2 weeks. Although modest ^42,43 and retrospective ⁴⁴ PJI-related studies showed that a single dose of an antibiotic earlier skin incision makes no difference to the sensitivity of samples, at that place is a adventure that growth of organisms in the laboratory could exist inhibited in the presence of antibiotics. ^45,46 It may therefore exist more beneficial to administer antibiotics immediately after sampling in case of suspected infection. Preferably, 5 or more than deep tissue or fluid samples should be collected, ^{7,39,41,47,48} ideally from the implant–bone interface. To avoid cantankerous-contamination, it is recommended that manipulation of the target expanse during this procedure is minimized ("no-touch-technique") and that divide, unused surgical instruments are used for each sample obtained. A simple sampling surgical instrument set can exist assembled for this purpose. ⁴¹ Superficial, skin, or sinus tract samples should be avoided, every bit these volition grow colonizing organisms with no predictive value for the causative pathogen of FRI. ⁴⁹ Swabs should non exist used due to their low yield compared with tissue cultures. ⁵⁰ The application of this set of principles regarding tissue sampling techniques has shown to significantly increase microbiological identification with more certainty of causative pathogens for Friday. ⁴¹

Bone needle aspiration and closed os needle biopsy, although important in other clinical infectious scenarios, practise not appear to be useful in FRI. Bone needle aspiration has primarily been used in pediatric osteomyelitis ⁵¹ and vertebral osteomyelitis ⁵² but has non been studied in Fri. Image-guided closed bone needle biopsy has not been investigated specifically in FRI. Airtight bone biopsy cultures in chronic osteomyelitis accept been shown to have a poor yield. ^53–56 Moreover, in Friday, surgical debridement is required for the collection of deep tissue samples. Therefore, the use of os needle aspiration or closed bone needle biopsy is not advocated in Friday.

Blood cultures should be taken in case of fever (unmarried oral temperature measurement of ≥38.3°C [101°F]). In cases of chronic/tardily-onset FRI, blood cultures showroom a depression yield rate, especially when compared with tissue cultures, because few of these Friday cases are associated with bacteremia.

Microbiology laboratory operating procedures for processing samples from FRI should be optimized. The relevant stages are as follows: (1) recognizing that these are deep implant-related samples and therefore processing each sample separately (no pooling of specimens), (ii) considering methods to disrupt potential biofilm, (3) culturing using advisable enrichment media (eg, blood civilization bottles ⁵⁷ ) for sufficient elapsing, and (four) total identification and a wide antibiogram on each organism to facilitate differentiation of strains and to allow several options for antimicrobial treatment.

Methods to facilitate biofilm disruption of tissue samples include vortexing with sterile glass chaplet, possibly with a bead manufacturing plant or vortexing lone. ^58,59 As organisms can exist in slow growth mode and small-scale numbers, enrichment broth cultures are essential. ^threescore In subacute or chronic infections, plate cultures are not necessary and have low sensitivity. Enrichment broths can be subcultured when cloudy or afterwards a divers menses (eg, five days). However, some organisms take longer to abound and require a later subculture. ⁶¹ Using automatic methods, cultures that contain pathogens are usually positive by day 3 and well-nigh are positive by day 5. ^62,63 To culture the slower growing organisms, cultures should proceed for 10–xiv days, depending on the detection method. When cultures are positive, all isolates should be worked up with standard laboratory identification methods, and an extended antibiogram should be obtained.

Sonication of difficult materials can be considered (eg, plates, intramedullary nails, cortical bone), but each component merely represents 1 sample. A semiquantitative cutoff bespeak for the number of colony-forming units helps to differentiate infection from contamination in PJI. ⁶⁴ Even so, every bit fracture fixation components may not be removed until some time afterward showtime of the surgery and surgical sites can go contaminated, these results also need to be interpreted in context with other diagnostic findings. ⁶⁵ In PJI, it is reported that sonication fluid culture is more sensitive than tissue civilization when antimicrobial agents are discontinued inside xiv days before surgery. ⁶⁴ The available evidence on sonication fluid sampling and tissue tests (molecular diagnostics and histopathology) for the diagnosis of FRI was analyzed in a recent systematic review ⁶⁶ and showed that for Friday, at that place is evidence that sonication fluid civilization may exist a useful adjunct to conventional tissue culture, but information technology is not superior. Overall, studies had variable "gold standard" definition criteria for comparison and poorly reported civilisation methods. The authors concluded that scientific evidence on the accurateness of sonication fluid civilisation for diagnosing Fri is deficient. A contempo written report on the performance of paired tissue and sonication cultures against a "golden-standard" of published clinical and composite clinical and microbiological definitions of infection constitute that tissue sampling is superior to sonication. ⁴⁷

In conclusion, a strict and clear protocol for tissue sampling and laboratory methods for Fri should exist adhered to optimize diagnosis, management, and long-term consequence. Although sonication seems to be a useful adjunct to conventional tissue culture, its existent added value in the diagnostic process of Friday still needs to be established.

Molecular Biology

Polymerase chain reaction (PCR) is a technique that can exist used to amplify bacterial DNA. In the past, the amplified PCR products were revealed by electrophoresis in an agarose gel (gel-based PCR). Over the past few years, near gel-based PCR assays have been replaced past real-time PCR. Existent-time PCR has the advantage of speed and existence less prone to cross contamination because information technology is performed in a airtight organisation. ⁶⁷ It is reported that molecular techniques performed on tissue, synovial fluid, or sonication fluid can confer valuable additional information in PJI, ⁶⁸ but in FRI, the testify is less clear. ⁶⁹ In the same systematic review, the diagnostic value of PCR techniques for Fri was studied. ⁶⁶ Two studies were included. ^70,71 The beginning written report reported that 16S ribosomal RNA PCR of deep wound swabs is inferior to standard tissue cultures. ^lxx Unfortunately, this observation is of limited value because deep tissue swabs are not standard of care because they exercise not sufficiently correspond the pathogens in the bone. ⁵⁰ The other study focused on the validation of multiplex PCR on sonication fluid. ⁷¹ It was found that the performance of sonication fluid PCR for the diagnosis of FRI was comparable to tissue civilization tests.

In conclusion, evidence for the diagnostic value of molecular techniques for FRI is scarce and based on pocket-size studies. Its benefit for diagnosing Friday has non however been established and further research and comeback of diagnostic performance is warranted.

Histopathology

In PJI, the presence of ≥v polymorphonuclear neutrophils per loftier-ability field (PMN/HPF) in v high-power fields observed from histopathologic assay of periprosthetic tissue, at ×400 magnification, is considered to be an of import intraoperative criterion for PJI. ^iv In the Friday consensus definition, the presence of visible microorganisms in deep tissue specimens using specific staining techniques for bacteria and fungi is regarded a confirmatory sign of FRI. ^seven The prove on histopathological examination of tissue specimens for FRI has also been reviewed ⁶⁶ and seems to be an underdeveloped surface area considering but 3 studies could be included. Recently, however, a study on the value of quantitative histopathology for the diagnosis of chronic/late-onset Fri has been published. ⁷² In this report, a novel bimodal arroyo was used to confirm or exclude infection. The complete absence of PMNs had a very loftier correlation with aseptic nonunion (specificity 98%, positive predictive value 98%). On the other hand, the presence of >v PMN/HPF was always associated with infection (specificity 100%; positive predictive value 100%). The combination of clinical signs, ≥2 microbiological cultures, and bimodal histopathological analysis (absent NPs vs. >five PMNs/HPF) improved diagnostic accuracy in up to 96.eight% of cases. The authors of this written report recommend that these histopathological criteria can be considered diagnostic of infection in chronic/late-onset FRI (eg, fracture nonunion).

In decision, the histopathologically confirmation of the presence of microorganisms past specific staining techniques on deep tissue specimens is a confirmatory sign of Friday. ^seven The value of histopathological criteria related to acute inflammatory jail cell infiltrates (absent PMNs vs. >5 PMNs/HPF) is now besides established for chronic/late-onset cases (ie, fracture nonunion) and should therefore exist included in the FRI consensus definition every bit a confirmatory criterion.

CONCLUSIONS

In summary, at that place is express scientific evidence regarding diagnostic criteria for FRI. Simply a small number of studies are available concerning the diagnostic accuracy of serum inflammatory markers, imaging modalities, tissue and sonication fluid sampling, molecular biology, and histopathology for Fri. Validation studies on the value of clinical parameters for diagnosing this condition are nonexistent. This lack of scientific evidence precludes the development of a diagnostic pathway that is solely based on sound evidence. The recently published Fri consensus definition seems an adequate commencement and offers clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It should also pb to a standardized clinical arroyo toward the diagnostic workup of patients with (suspected) Friday.

Apart from the established criteria, there is growing evidence that nuclear medicine imaging and histopathology should play a role in this diagnostic process. During a second consensus coming together in 2018—including not merely experts from the AO Foundation and the EBJIS but also from the Orthopaedic Trauma Clan and the PRO-Implant foundation—it was therefore decided that these 2 criteria should exist included in the FRI consensus definition. Effigy 4 shows an update on the electric current diagnostic criteria. Key recommendations for the diagnosis of FRI are displayed in Table ane. Inside the short period since publication, the consensus definition of FRI has already been practical in the pattern of ii clinical studies. ^72,73 The continued adoption and evaluation of this definition in further clinical studies will let validation of the definition and ameliorate the quality of comparative upshot studies in the hereafter.

Figure 4.:

Descriptive flow nautical chart of the diagnostic criteria of Fri. Adapted from Metsemakers et al, Injury 2018. ^vii Reprinted from Metsemakers WJ et al., Fracture-related infection: a consensus on definition from an international good grouping. 2018 Injury:49/Event 6, with permission from Elsevier. All permission requests for this paradigm should exist made to the copyright holder.

Table one.:

Key Recommendations

ACKNOWLEDGMENTS

The authors specifically thank the Anti-Infection Task Force (AOTK System; Claas Albers) and the Clinical Priority Program Os Infection (AOTrauma; Philipp Buescher) for their back up of the consensus meetings that were convened in 2016 (Davos, Switzerland) and 2018 (Zürich, Switzerland). Furthermore, the authors thank Jolien Onsea (Department of Trauma Surgery, University Hospitals Leuven) and Lois Wallach (AOTK System) for their assistance in preparing and proofreading this manuscript.

Members of the FRI Consensus Group: West-J. Metsemakers, Doc, PhD (chair): Department of Trauma Surgery, University Hospitals Leuven, Leuven, Belgium; Due west. T. Obremskey, Doc, MPH (chair): Department of Orthopaedic Surgery and Rehabilitation, Vanderbilt Academy Medical Heart, Nashville, TN; Yard. A. McNally, MD, FRCS(Orth) (Chair): The Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, Uk; Nick Athanasou, Physician, PhD, MRCP, FRCPath; The Os Infection Unit, Nuffield Orthopaedic Heart, Oxford Academy Hospitals, Oxford, Uk; B. 50. Atkins, Doctor, MBBS, MSc, FRCP, FRCPath: The Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford Academy Hospitals, Oxford, Uk; Olivier Borens, Physician, PhD: Orthopedic Department of Septic Surgery, Orthopaedic-Trauma Unit, Department for the Musculoskeletal Arrangement, CHUV, Lausanne, Switzerland; Melissa Depypere, Physician: Section of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; Henrik Eckardt, MD: Section of Orthopaedic and Trauma Surgery, University Hospital Basel, Basel, Switzerland; Kenneth A. Egol, MD: Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, NY; William Foster, Md: Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, VA, USA; Austin T. Fragomen, MD: Infirmary for Special Surgery, Limb Lengthening & Complex Reconstruction Service, New York, NY; M. A. M. Govaert, MD, PhD: Department of Trauma Surgery, University of Utrecht, University Medical Middle Utrecht, Utrecht, the Netherlands; Sven Hungerer, MD: Section of Joint Surgery and Arthroplasty, Trauma Center Murnau, Murnau Germany and Paracelsus Medical University (PMU) Salzburg, Salzburg, Austria; Stephen L. Kates, Doctor: Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, VA, USA; R. Kuehl, Medico: Section of Infectious Diseases and Infirmary Epidemiology, University Hospital of Basel, Basel, Switzerland; Leonard Marais, Physician, PhD: Department of Orthopaedics, School of Clinical Medicine, University of KwaZulu-Natal, Durban, Due south Africa; Ian Mcfadyen, MD: Department of Orthopaedic Surgery, University Hospitals of North Midlands, Stoke-on-Trent, Britain; 1000. Morgenstern: Section of Orthopaedic and Trauma Surgery, University Infirmary Basel, Basel, Switzerland; T. Fintan Moriarty, PhD: AO Research Institute Davos, Davos, Switzerland; Peter Ochsner, Md; Medical University Basel, Basel, Switzerland; Alex Ramsden, Dr.; The Bone Infection Unit, Nuffield Orthopaedic Middle, Oxford University Hospitals, Oxford, Uk; Michael Raschke, MD, PhD: Department of Trauma Surgery, University Infirmary of Münster, Münster, Germany; R. Geoff Richards, PhD: AO Research Institute Davos, Davos, Switzerland; Carlos Sancineto, Medico: Department of Orthopaedics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Charalampos Zalavras, MD, PhD: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA; Eric Senneville, MD, PhD: Section of Infectious Diseases, Gustave Dron Hospital, University of Lille, Lille, France; Andrej Trampuz, Medico: Centre for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Wellness, Berlin, Frg; Michael H.J. Verhofstad, MD, PhD: Section of Trauma Surgery, Erasmus University Medical Centre, Rotterdam, kingdom of the netherlands; and Werner Zimmerli, Md: Interdisciplinary Unit of measurement for Orthopedic Infections, Kantonsspital Baselland, Switzerland.

REFERENCES

1. Metsemakers WJ, Kortram K, Morgenstern K, et al. Definition of infection later on fracture fixation: a systematic review of randomized controlled trials to evaluate current do. Injury. 2018;49:497–504.

• Cited Here |
• PubMed

2. Metsemakers WJ, Moriarty TF, Morgenstern Chiliad, et al. Letter to the editor: new definition for periprosthetic joint infection: from the workgroup of the musculoskeletal infection Lodge. Clin Orthop Relat Res. 2016;474:2726–2727.

3. Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic articulation infection: from the Workgroup of the Musculoskeletal Infection Lodge. Clin Orthop Relat Res. 2011;469:2992–2994.

4. Parvizi J, Tan TL, Goswami M, et al. The 2018 definition of periprosthetic hip and genu infection: an evidence-based and validated criteria. J Arthroplasty. 2018;33:1309–1314 e1302.

five. Morgenstern Thousand, Moriarty TF, Kuehl R, et al. International survey among orthopaedic trauma surgeons: lack of a definition of fracture-related infection. Injury. 2018;49:491–496.

• Cited Here |
• PubMed

6. Govaert GAM, Glaudemans A, Ploegmakers JJW, et al. Diagnostic strategies for posttraumatic osteomyelitis: a survey among Dutch medical specialists demonstrates the need for a consensus protocol. Eur J Trauma Emerg Surg. 2018;44:417–426.

• Cited Here |
• PubMed

7. Metsemakers WJ, Morgenstern Grand, McNally MA, et al. Fracture-related infection: a consensus on definition from an international practiced grouping. Injury. 2018;49:505–510.

• Cited Hither |
• PubMed

viii. Cats-Baril Due west, Gehrke T, Huff K, et al. International consensus on periprosthetic joint infection: clarification of the consensus process. Clin Orthop Relat Res. 2013;471:4065–4075.

nine. Bezstarosti H, Van Lieshout EMM, Voskamp LW, et al. Insights into treatment and consequence of fracture-related infection: a systematic literature review. Curvation Orthop Trauma Surg. 2019;139:61–72.

x. Nicolas-Avila JA, Adrover JM, Hidalgo A. Neutrophils in homeostasis, immunity, and cancer. Immunity. 2017;46:15–28.

11. Teng TS, Ji AL, Ji XY, et al. Neutrophils and amnesty: from bactericidal action to being conquered. J Immunol Res. 2017;2017:9671604.

• Cited Here |
• PubMed

12. Kraft CN, Kruger T, Westhoff J, et al. CRP and leukocyte-count afterwards lumbar spine surgery: fusion vs. nucleotomy. Acta Orthop. 2011;82:489–493.

• Cited Here

13. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Forepart Immunol. 2018;9:754.

• Cited Here

14. Lu J, Marnell LL, Marjon KD, et al. Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature. 2008;456:989–992.

xv. Neumaier Thousand, Scherer MA. C-reactive protein levels for early detection of postoperative infection later on fracture surgery in 787 patients. Acta Orthop. 2008;79:428–432.

• Cited Here

sixteen. Kunakornsawat Due south, Tungsiripat R, Putthiwara D, et al. Postoperative kinetics of C-reactive protein and erythrocyte sediment rate in one-, two-, and multilevel posterior spinal decompressions and instrumentations. Global Spine J. 2017;7:448–451.

• Cited Here

17. Brownish KA, Brain SD, Pearson JD, et al. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368:157–169.

18. Chmielewski PP, Strzelec B. Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review. Folia Morphol (Warsz). 2018;77:171–178.

xix. Ettinger M, Calliess T, Kielstein JT, et al. Circulating biomarkers for discrimination between aseptic articulation failure, low-grade infection, and loftier-grade septic failure. Clin Infect Dis. 2015;61:332–341.

20. Fischer CL, Gill C, Forrester MG, et al. Quantitation of "acute-phase proteins" postoperatively: value in detection and monitoring of complications. Am J Clin Pathol. 1976;66:840–846.

21. Scherer MA, Neumaier M, von Gumppenberg S. C-reactive poly peptide in patients who had operative fracture treatment. Clin Orthop Relat Res. 2001:287–293.

22. van den Kieboom J, Bosch P, Plate JDJ, et al. Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis. Bone Articulation J. 2018;100B:1542–1550.

23. Govaert GA, FF IJ, McNally M, et al. Accuracy of diagnostic imaging modalities for peripheral post-traumatic osteomyelitis—a systematic review of the recent literature. Eur J Nucl Med Mol Imaging. 2017;44:1393–1407.

24. Goebel M, Rosa F, Tatsch K, et al. Diagnosis of chronic osteitis of the bones in the extremities: relative value of F-18 FDG-PET [in German]. Unfallchirurg. 2007;110:859–866.

25. Kaim A, Ledermann HP, Bongartz M, et al. Chronic post-traumatic osteomyelitis of the lower extremity: comparison of magnetic resonance imaging and combined os scintigraphy/immunoscintigraphy with radiolabelled monoclonal antigranulocyte antibodies. Skeletal Radiol. 2000;29:378–386.

26. Govaert GA, Glaudemans AW. Nuclear medicine imaging of posttraumatic osteomyelitis. Eur J Trauma Emerg Surg. 2016;42:397–410.

• Cited Here |
• PubMed

27. Glaudemans AW, Prandini N, DI Girolamo M, et al. Hybrid imaging of musculoskeletal infections. Q J Nucl Med Mol Imaging. 2018;62:3–13.

• Cited Here |
• PubMed

28. Ballani NS, Al-Huda FA, Khan HA, et al. The value of quantitative uptake of (99m)Tc-MDP and (99m)Tc-HMPAO white blood cells in detecting osteomyelitis in violated peripheral bones. J Nucl Med Technol. 2007;35:91–95.

29. Meller J, Koster G, Liersch T, et al. Chronic bacterial osteomyelitis: prospective comparison of (18)F-FDG imaging with a dual-head coincidence camera and (111)In-labelled autologous leucocyte scintigraphy. Eur J Nucl Med Mol Imaging. 2002;29:53–sixty.

30. Glaudemans AW, de Vries EF, Vermeulen LE, et al. A large retrospective single-heart study to define the all-time image acquisition protocols and interpretation criteria for white blood cell scintigraphy with (ix)(9)mTc-HMPAO-labelled leucocytes in musculoskeletal infections. Eur J Nucl Med Mol Imaging. 2013;40:1760–1769.

31. Horger Thousand, Eschmann SM, Pfannenberg C, et al. The value of SPET/CT in chronic osteomyelitis. Eur J Nucl Med Mol Imaging. 2003;30:1665–1673.

32. Govaert GAM, Bosch P, FFA IJ, et al. High diagnostic accuracy of white blood cell scintigraphy for fracture related infections: results of a large retrospective unmarried-center report. Injury. 2018;49:1085–1090.

33. Glaudemans AW, Galli F, Pacilio Grand, et al. Leukocyte and bacteria imaging in prosthetic articulation infection. Eur Jail cell Mater. 2013;25:61–77.

34. Lemans JVC, Hobbelink MGG, FFA IJ, et al. The diagnostic accuracy of (18)F-FDG PET/CT in diagnosing fracture-related infections. Eur J Nucl Med Mol Imaging. 2019;46:999–1008.

35. Hartmann A, Eid K, Dora C, et al. Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Eur J Nucl Med Mol Imaging. 2007;34:704–714.

36. Shemesh Southward, Kosashvili Y, Groshar D, et al. The value of 18-FDG PET/CT in the diagnosis and direction of implant-related infections of the tibia: a case serial. Injury. 2015;46:1377–1382.

37. van Vliet KE, de Jong VM, Termaat MF, et al. FDG-PET/CT for differentiating between hygienic and septic delayed union in the lower extremity. Arch Orthop Trauma Surg. 2018;138:189–194.

38. Wenter Five, Muller JP, Albert NL, et al. The diagnostic value of [(eighteen)F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection. Eur J Nucl Med Mol Imaging. 2016;43:749–761.

39. Atkins BL, Athanasou N, Deeks JJ, et al. Prospective evaluation of criteria for microbiological diagnosis of prosthetic-articulation infection at revision arthroplasty: the OSIRIS Collaborative Study Grouping. J Clin Microbiol. 1998;36:2932–2939.

twoscore. McNally MA. Infection afterwards fracture. In: Kates SL, Borens O, eds Principles of Orthopedic Infection Management. New York, NY: AO Trauma Thieme Verlag; 2016:139–165.

• Cited Here

41. Hellebrekers P, Rentenaar RJ, McNally MA, et al. Getting information technology right first time: the importance of a structured tissue sampling protocol for diagnosing fracture-related infections. Injury. 2019 [epub alee of print].

• Cited Here

42. Perez-Prieto D, Portillo ME, Puig-Verdie L, et al. Preoperative antibiotic prophylaxis in prosthetic joint infections: not a business for intraoperative cultures. Diagn Microbiol Infect Dis. 2016;86:442–445.

43. Bedencic G, Kavcic Grand, Faganeli N, et al. Does preoperative antimicrobial prophylaxis influence the diagnostic potential of periprosthetic tissues in hip or knee infections? Clin Orthop Relat Res. 2016;474:258–264.

44. Wouthuyzen-Bakker M, Tornero E, Claret K, et al. Withholding preoperative antibiotic prophylaxis in human knee prosthesis revision: a retrospective analysis on culture results and risk of infection. J Arthroplasty. 2017;32:2829–2833.

45. Miller NS, Rogan D, Orr BL, et al. Comparison of BD Bactec Plus blood civilisation media to VersaTREK Redox claret culture media for detection of bacterial pathogens in simulated adult blood cultures containing therapeutic concentrations of antibiotics. J Clin Microbiol. 2011;49:1624–1627.

46. Grupper G, Nicolau DP, Aslanzadeh J, et al. Effects of clinically meaningful concentrations of antipseudomonal beta-lactams on time to detection and organism growth in claret culture bottles. J Clin Microbiol. 2017;55:3502–3512.

47. Dudareva M, Barrett L, Figtree Thousand, et al. Sonication versus tissue sampling for diagnosis of prosthetic joint and other orthopaedic device-related infections. J Clin Microbiol. 2018;56.

• Cited Here

48. Dudareva Thou, Barrett L, Morgenstern Chiliad, et al. An evidence base for tissue sampling and culture interpretation in fracture-related infection. Orthop Proc. 2018;100B:15.

• Cited Here

49. Mackowiak PA, Jones SR, Smith JW. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA. 1978;239:2772–2775.

50. Aggarwal VK, Higuera C, Deirmengian G, et al. Swab cultures are non as effective equally tissue cultures for diagnosis of periprosthetic articulation infection. Clin Orthop Relat Res. 2013;471:3196–3203.

51. Schlung JE, Bastrom TP, Roocroft JH, et al. Femoral neck aspiration aids in the diagnosis of osteomyelitis in children with septic hip. J Pediatr Orthop. 2018;38:532–536.

52. Pupaibool J, Vasoo S, Erwin PJ, et al. The utility of image-guided percutaneous needle aspiration biopsy for the diagnosis of spontaneous vertebral osteomyelitis: a systematic review and meta-analysis. Spine J. 2015;15:122–131.

53. Beroukhim G, Shah R, Bucknor MD. Factors predicting positive culture in CT-guided bone biopsy performed for suspected osteomyelitis. AJR Am J Roentgenol. 2019;212:620–624.

54. Hoang D, Fisher S, Oz OK, et al. Percutaneous CT guided os biopsy for suspected osteomyelitis: diagnostic yield and affect on patient'due south treatment change and recovery. Eur J Radiol. 2019;114:85–91.

55. Said N, Chalian M, Play a trick on MG, et al. Percutaneous paradigm-guided os biopsy of osteomyelitis in the foot and pelvis has a low impact on guiding antibiotics management: a retrospective analysis of 60 os biopsies. Skeletal Radiol. 2019;48:1385–1391.

56. Wu JS, Gorbachova T, Morrison WB, et al. Imaging-guided os biopsy for osteomyelitis: are in that location factors associated with positive or negative cultures? AJR Am J Roentgenol. 2007;188:1529–1534.

57. Peel TN, Dylla BL, Hughes JG, et al. Improved diagnosis of prosthetic articulation infection by culturing periprosthetic tissue specimens in blood culture bottles. MBio. 2016;7:e01776–e01715.

• Cited Here

58. Roux AL, Sivadon-Tardy V, Bauer T, et al. Diagnosis of prosthetic articulation infection past beadmill processing of a periprosthetic specimen. Clin Microbiol Infect. 2011;17:447–450.

59. Suren C, Harrasser N, Pohlig F, et al. Prospective analysis of a sterile, semi-automated tissue biopsy homogenization method in the diagnosis of prosthetic articulation infections. In Vivo. 2017;31:937–942.

• Cited Hither |
• PubMed

60. Hughes HC, Newnham R, Athanasou Northward, et al. Microbiological diagnosis of prosthetic joint infections: a prospective evaluation of four bacterial culture media in the routine laboratory. Clin Microbiol Infect. 2011;17:1528–1530.

61. Schafer P, Fink B, Sandow D, et al. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis. 2008;47:1403–1409.

62. Minassian AM, Newnham R, Kalimeris E, et al. Use of an automated blood civilisation system (BD BACTEC) for diagnosis of prosthetic joint infections: easy and fast. BMC Infect Dis. 2014;14:233.

• Cited Here |
• PubMed

63. Patel R. MALDI-TOF MS for the diagnosis of infectious diseases. Clin Chem. 2015;61:100–111.

64. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357:654–663.

65. Jonsson EO, Johannesdottir H, Robertsson O, et al. Bacterial contamination of the wound during main full hip and human knee replacement: median thirteen years of follow-up of 90 replacements. Acta Orthop. 2014;85:159–164.

• Cited Hither

66. Onsea J, Depypere Thousand, Govaert G, et al. Accurateness of tissue and sonication fluid sampling for the diagnosis of fracture-related infection: a systematic review and critical appraisal. J Bone Articulation Infect. 2018;iii:173–181.

• Cited Hither

67. Hartley JC, Harris KA. Molecular techniques for diagnosing prosthetic articulation infections. J Antimicrob Chemother. 2014;69(suppl 1):i21–i24.

68. Morgenstern C, Cabric S, Perka C, et al. Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection. Diagn Microbiol Infect Dis. 2018;90:115–119.

69. Morgenstern K, Kuhl R, Eckardt H, et al. Diagnostic challenges and future perspectives in fracture-related infection. Injury. 2018;49(suppl one):S83–S90.

70. Omar Thousand, Suero EM, Liodakis East, et al. Diagnostic performance of swab PCR as an alternative to tissue culture methods for diagnosing infections associated with fracture fixation devices. Injury. 2016;47:1421–1426.

71. Renz Due north, Cabric S, Morgenstern C, et al. Value of PCR in sonication fluid for the diagnosis of orthopedic hardware-associated infections: has the molecular era arrived? Injury. 2018;49:806–811.

72. Morgenstern M, Athanasou NA, Ferguson JY, et al. The value of quantitative histology in the diagnosis of fracture-related infection. Os Joint J. 2018;100B:966–972.

73. Govaert GAM, Hobbelink MGG, Reininga IHF, et al. The accuracy of diagnostic imaging techniques in patients with a suspected fracture-related infection (IFI) trial: report protocol for a prospective multicenter cohort study. BMJ Open. 2019;9:e027772.

• Cited Here

Keywords:

fracture-related infection; diagnosis; diagnostic criteria; definition; clinical criteria; medical imaging; histopathology; microbiology; serum inflammatory markers; fracture; infection

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.

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Source: https://journals.lww.com/jorthotrauma/Fulltext/2020/01000/Diagnosing_Fracture_Related_Infection__Current.3.aspx

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