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A judicious, well-planned bone and soft tissue debridement remains one of the cornerstones of state-of-the-art treatment of fracture-related infection (FRI). Meticulous surgical excision of all non-viable tissue can, however, lead to the creation of large soft tissue defects. The management of these defects is complex and numerous factors need to be considered when selecting the most appropriate approach. This narrative review summarizes the current evidence with respect to soft tissue management in patients diagnosed with FRI. Specifically we discuss the optimal timing for tissue closure following debridement in cases of FRI, the need for negative microbiological culture results from the surgical site as a prerequisite for definitive wound closure, the optimal type of flap in case of large soft tissue defects caused by FRI and the role of negative pressure wound therapy (NPWT) in FRI. Finally, recommendations are made with regard to soft tissue management in FRI that should be useful for clinicians in daily clinical practice. Level of evidence Level V. [ABSTRACT FROM AUTHOR]

Introduction: Fracture-related infection (FRI) represents a challenging clinical scenario. Limited evidence exists regarding treatment failure after initial management of FRI. The objective of our investigation was to determine incidence and risk factors for treatment failure in FRI. Materials and methods: We conducted a retrospective review of patients treated for FRI between 2011 and 2015 at three level 1 trauma centers. One hundred and thirty-four patients treated for FRI were identified. Demographic and clinical variables were extracted from the medical record. Treatment failure was defined as the need for repeat debridement or surgical revision seven or more days after the presumed final procedure for infection treatment. Univariate comparisons were conducted between patients who experienced treatment failure and those who did not. Multivariable logistic regression was conducted to identify independent associations with treatment failure. Results: Of the 134 FRI patients, 51 (38.1%) experienced treatment failure. Patients who failed were more likely to have had an open injury (31% versus 17%; p = 0.05), to have undergone implant removal (p = 0.03), and additional index I&D procedures (3.3 versus 1.6; p < 0.001). Most culture results identified a single organism (62%), while 15% were culture negative. Treatment failure was more common in culture-negative infections (p = 0.08). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common organism associated with treatment failure (29%; p = 0.08). Multivariate regression demonstrated a statistically significant association between treatment failure and two or more irrigation and debridement (I&D) procedures (OR 13.22, 95% CI 4.77–36.62, p < 0.001) and culture-negative infection (OR 4.74, 95% CI 1.26–17.83, p = 0.02). Conclusions: The rate of treatment failure following FRI continues to be high. Important risk factors associated with treatment failure include open fracture, implant removal, and multiple I&D procedures. While MRSA remains common, culture-negative infection represents a novel risk factor for failure, suggesting aggressive treatment of clinically diagnosed cases remains critical even without positive culture data. Level of evidence: Retrospective cohort study; Level III. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review determined the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in fracture-related infection (FRI) patients between 1990 and 2018. Methods: A systematic literature search on treatment and outcome of critical-sized bone defects in FRI was performed. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, Ilizarov bone transport, and bone transport combined with local antibiotics. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period. Results: Fifty studies were included, describing 1530 patients, the tibia was affected in 82%. Mean age was 40 years (range 6–80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1–624) and mean follow-up 51 months (range 6–126). After initial protocolized treatment, FRI was cured in 83% (95% CI 79–87) of all cases, increasing to 94% (95% CI 92–96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6–11) and amputation in 3% (95% CI 2–3). Final outcomes overlapped across treatment strategies. Conclusion: Results should be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed to improve reliability of future studies. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the accuracy of available nuclear imaging modalities in the diagnosis of suspected fracture-related infection (FRI).Methods: We conducted a comprehensive literature search of PubMed, EMBASE and the Cochrane Library to retrieve diagnostic accuracy studies in which FRI was investigated using different nuclear imaging modalities. The pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratios were constructed using the bivariate meta-analysis framework, while the superior index was pooled using Bayesian network meta-analysis.Results: 22 eligible studies (1,565 patients) were included in the quantitative analysis. A broad overlapping confidence interval (CI) of pooled sensitivity was observed among bone scintigraphy (0.94; 95% CI 0.85-0.98), 18F-FDG PET and PET/CT (0.91; 95% CI 0.85-0.94) and leukocyte scintigraphy (0.86; 95% CI 0.53-0.97). Bone scintigraphy (0.34; 95% CI 0.08-0.75) seemed to be less specific than all the other modalities, while leukocyte scintigraphy (0.96, 95% CI 0.92-0.98) was notably more specific than 18F-FDG PET and PET/CT (0.78; 95% CI 0.69-0.85). Based on the superiority index, 18F-FDG PET/CT (3.78; 95% CI 0.14-11.00), 18F-FDG PET (2.98; 95% CI 0.14-9.00) and leukocyte scintigraphy (1.51; 95% CI 0.11-7.00) all achieved high accuracy in detecting FRI.Conclusion: Bone scintigraphy is a highly sensitive nuclear imaging technique but lacks the specificity needed to unequivocally differentiate among various conditions suspected to be FRI. Leukocyte scintigraphy, 18F-FDG PET/CT and PET all present good satisfactory accuracy for the diagnosis of FRI, but their costs should be further reduced to promote their wide application. [ABSTRACT FROM AUTHOR]

Introduction: Infection is a common complication of open fractures potentially leading to nonunion, functional loss, and even amputation. Perioperative antibiotic prophylaxis (PAP) is standard practice for infection prevention in the management of open fractures. However, optimal duration of PAP remains controversial. The objectives were to assess whether PAP duration is independently associated with infection in open fractures and if administration of PAP beyond the commonly-recommended limit of 72 h has any effect on the infection rate. Materials and methods: Over a 14-year period from 2003 to 2017, 530 skeletally-mature patients with operatively-treated, non-pathologic, long-bone open fractures were treated at one institution. Twenty-eight patients were excluded because of death or loss to follow-up and the remaining 502 patients (with 559 open fractures) who completed a 24-month follow-up were included in this retrospective study. The outcome was fracture-related infection (FRI), defined by the criteria of a recent consensus definition. A logistic generalized estimating equations regression model was conducted, including PAP duration and variables selected by a least absolute shrinkage and selection operator (LASSO) method, to assess the association between PAP duration and FRI. Propensity score analysis using a 72-h cut-off was performed to further cope with confounding. Results: PAP duration, adjusted for the LASSO selected predictors, was independently associated with FRI (OR: 1.11 [95%CI, 1.04–1.19] for every one-day increase in PAP duration, p = 0.003). PAP duration longer than 72 h did not significantly increase the odds for FRI compared to shorter durations (p = 0.06, analysis adjusted for propensity score). Conclusions: This study found no evidence that administration of prophylactic antibiotics beyond 72 h in patients with long-bone open fractures is warranted. Analyses adjusted for known confounders even revealed a higher risk for FRI for longer PAP. However, this effect cannot necessarily be considered as causal and further research is needed. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients' short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.Level of evidence: Level V. [ABSTRACT FROM AUTHOR]

Introduction: Osteomyelitis is an increasing burden on the society especially due to the emergence of multiple drug-resistant organisms. The lack of a central registry that prospectively collects data on patient risk factors, laboratory test results, treatment modalities, serological analysis results, and outcomes has hampered the research effort that could have improved and provided guidelines for treatments of bone infections. The current manuscript describes the lessons learned in setting up a multi-continent registry.Materials and Methods: This multicenter, international registry was conducted to prospectively collect essential patient, clinical, and surgical data with a 1-year follow-up period. Patients 18 years or older with confirmed S. aureus long bone infection through fracture fixation or arthroplasty who consented to participate in the study were included. The outcomes using the Short Form 36 Health Survey Questionnaire (version 2), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at baseline and at 1 month, 6 months, and 12 months. Serological samples were collected at follow-ups.Results: Contract negotiation with a large number of study sites was difficult; obtaining ethics approvals were time-consuming but straightforward. The initial patient recruitment was slow, leading to a reduction of target patient number from 400 to 300 and extension of enrollment period. Finally, 292 eligible patients were recruited by 18 study sites (in 10 countries of 4 continents, Asia, North and South America, and Central Europe). Logistical and language barriers were overcome by employing courier service and local monitoring personnel.Conclusions: Multicenter registry is useful for collecting a large number of cases for analysis. A well-defined data collection practice is important for data quality but challenging to coordinate with the large number of study sites. [ABSTRACT FROM AUTHOR]

Introduction: Several scores were introduced to diagnose and to classify osteomyelitis in practice. Mouse models are often used to study the pathophysiology of bone infection and to test therapeutic strategies. Aim of the present study was to design a score to diagnose and quantify implant-associated infection in a murine experimental model.Materials and Methods: Four independent parameters were developed: existence of callus, consolidation of the fracture, structural changes of the medullary cavity and number of bacteria. The score was assessed in a standardized implant-associated mouse model with 35 BALB/c-mice. The left femur was osteotomized, fixed by a titanium locking plate and infection was induced by inoculation of Staphylococcus aureus into the fracture gap. For the sham group, the procedure was performed without inoculation of bacteria. The score was assessed on days 7, 14 and 28. Each item of the score showed lower values for the infection group compared to the controls after 4 weeks.Results: Regardless of the assessed time point, the overall total score was significantly higher in the control group compared to the infection group (p < 0.0001). Analysis revealed a sensitivity of 0.85, specificity of 1.0, negative predictive value of 0.67 and positive predictive value of 1.0.Conclusion: The proposed score assessing severity of fracture-related infection in an implant-associated murine model was easy to access, feasible to diagnose and estimate bone healing and infection in a murine bone infection with a high sensitivity. Therefore, this score might be a useful tool to quantify infection-related changes after fracture in further future preclinical studies. [ABSTRACT FROM AUTHOR]

Introduction: Standardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients.Methods: A comprehensive search was performed in all scientific literature since 1990. Studies in English that described surgical patient series for treatment of FRI were included. Data were collected on diagnostic criteria for FRI, classifications used, surgical treatments, follow-up protocols, and overall outcome. A systematic review was performed according to the PRISMA statement. Proportions and weighted means were calculated.Results: The search yielded 2051 studies. Ninety-three studies were suitable for inclusion, describing 3701 patients (3711 fractures) with complex FRI. The population consisted predominantly of male patients (77%), with the tibia being the most commonly affected bone (64%), and a mean of three previous operations per patient. Forty-three (46%) studies described FRI at one specific location. Only one study (1%) used a standardized definition for infection. A total of nine different classifications were used to guide treatment protocols, of which Cierny and Mader was used most often (36%). Eighteen (19%) studies used a one-stage, 50 (54%) a two-stage, and seven (8%) a three-stage surgical treatment protocol. Ten studies (11%) used mixed protocols. Antibiotic protocols varied widely between studies. A multidisciplinary approach was mentioned in only 12 (13%) studies.Conclusions: This extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago. Internationally accepted guidelines are urgently required to improve the quality of care for patients suffering from this significant complication. [ABSTRACT FROM AUTHOR]