The FRI classification - A new classification of fracture-related infections.

AIM: To identify the most relevant factors with respect to the management of fracture-related infection (FRI) and to develop a comprehensive FRI classification that guides decision-making and allows scientific comparison. METHOD: An international group of FRI experts determined the preconditions, purpose, primary factors for inclusion, format and detailed description of the elements of an FRI classification through a consensus driven process. RESULTS: Three major elements were identified and grouped together in the FRI Classification: Fracture (F), Related patient factors (R) and Impairment of soft tissues (I). Each element was divided into five levels of complexity. Fractures can be healed (F1) or unhealed (F2-5). Patients may be fully healthy (R1) or have 4 levels of compromise, with and without end-organ damage (R2-5). Soft tissue condition ranges from well vascularized and easily closed (I1) to major skin defects requiring free flaps (I4). In all three elements, the fifth level (F5, R5 or I5) describes a patient who has an unreconstructible bone, soft tissue envelope or is not fit for surgery. CONCLUSION: The FRI classification, which is based on the three major elements Fracture (F), Related patient factors (R) and Impairment of soft tissues (I) is intended to guide decision-making and improve the quality of scientific reporting for FRIs in the future. The proposed classification is based on expert opinion and therefore an essential next step is clinical validation, in order to realize the ultimate goal of improving outcomes in the management of FRI.

The surgical management of fracture-related infection. Surgical strategy selection and the need for early surgical intervention.

The aim of this narrative review is to describe the various surgical management strategies employed in fracture-related infection (FRI), to explore how they are selected and discuss the rationale for early surgical intervention. Surgical treatment options in patients with FRI include debridement, antibiotics and implant retention (DAIR), revision (exchange) or removal. In selecting a treatment strategy, a variety of factors need to be considered, including the condition of the bone, soft tissues, host and causative microorganism. Irrespective of the selected treatment strategy, prompt surgical intervention should be considered in order to confirm the diagnosis of an FRI, to identify the causative organism, remove necrotic or non-viable tissue that can serve as a nidus for ongoing infection, ensure a healthy soft tissue envelope and to prevent the vicious cycle of infection associated with skeletal and/or implant instability. Ultimately, the objective is to prevent the establishment of a persistent infection. Urgent surgery may be indicated in case of active, progressive disease with systemic deterioration, local progression of infection, deterioration of soft tissues, or progressive fracture instability. In case of static disease, the patient should be monitored closely and surgery can be performed on an elective basis, allowing adequate time for optimisation of the host through risk factor modification, optimisation of the soft tissues and careful planning of the surgery.

Key aspects of soft tissue management in fracture-related infection: recommendations from an international expert group.

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.

The global burden of fracture-related infection: can we do better?

Fracture-related infection is a major complication related to musculoskeletal injuries that not only has important clinical consequences, but also a substantial socioeconomic impact. Although fracture-related infection is one of the oldest disease entities known to mankind, it has only recently been defined and, therefore, its global burden is still largely unknown. In this Personal View, we describe the origin of the term fracture-related infection, present the available data on its global impact, and discuss important aspects regarding its prevention and management that could lead to improved outcomes in both high-resource and low-resource settings. We also highlight the need for health-care systems to be adequately compensated for the high cost of human resources (trained staff) and well-equipped facilities required to adequately care for these complex patients. Our aim is to increase awareness among clinicians and policy makers that fracture-related infection is a disease entity that deserves prioritisation in terms of research, with the goal to standardise treatment and improve patient outcomes on a global scale.

Diagnosis of fracture-related infection in patients without clinical confirmatory criteria: an international retrospective cohort study.

Background: fracture-related infection (FRI) remains a serious complication in orthopedic trauma. To standardize daily clinical practice, a consensus definition was established, based on confirmatory and suggestive criteria. In the presence of clinical confirmatory criteria, the diagnosis of an FRI is evident, and treatment can be started. However, if these criteria are absent, the decision to surgically collect deep tissue cultures can only be based on suggestive criteria. The primary study aim was to characterize the subpopulation of FRI patients presenting without clinical confirmatory criteria (fistula, sinus, wound breakdown, purulent wound drainage or presence of pus during surgery). The secondary aims were to describe the prevalence of the diagnostic criteria for FRI and present the microbiological characteristics, both for the entire FRI population. Methods: a multicenter, retrospective cohort study was performed, reporting the demographic, clinical and microbiological characteristics of 609 patients (with 613 fractures) who were treated for FRI based on the recommendations of a multidisciplinary team. Patients were divided in three groups, including the total population and two subgroups of patients presenting with or without clinical confirmatory criteria. Results: clinical and microbiological confirmatory criteria were present in 77 % and 87 % of the included fractures, respectively. Of patients, 23 % presented without clinical confirmatory criteria, and they mostly displayed one (31 %) or two (23 %) suggestive clinical criteria (redness, swelling, warmth, pain, fever, new-onset joint effusion, persisting/increasing/new-onset wound drainage). The prevalence of any suggestive clinical, radiological or laboratory criteria in this subgroup was 85 %, 55 % and 97 %, respectively. Most infections were monomicrobial (64 %) and caused by Staphylococcus aureus. Conclusion: clinical confirmatory criteria were absent in 23 % of the FRIs. In these cases, the decision to operatively collect deep tissue cultures was based on clinical, radiological and laboratory suggestive criteria. The combined use of these criteria should guide physicians in the management pathway of FRI. Further research is needed to provide guidelines on the decision to proceed with surgery when only these suggestive criteria are present.

Antibiotic bead pouch versus negative pressure wound therapy at initial management of AO/OTA 42 type IIIB open tibia fracture may reduce fracture related infection: A retrospective analysis of 113 patients.

INTRODUCTION: Fracture related infection (FRI) may be a devastating complication of open tibial shaft fractures. We sought to determine if antibiotic bead pouch, negative pressure wound therapy, or negative pressure wound therapy over antibiotic beads as the initial coverage method for type IIIB open tibial shaft fractures is associated with risk of FRI. PATIENTS AND METHODS: Retrospective cohort study with radiograph and chart review of patients aged ≥16 years with isolated, displaced, extra-articular, Gustilo-Anderson type IIIB open diaphyseal AO/OTA 42 tibial fractures requiring rotational or free tissue transfer for soft tissue coverage at one Level 1 trauma center between 2007 and 2020. An association of dressing applied at the first surgical debridement (application of antibiotic bead pouch, negative pressure wound therapy, or combined therapy) with a primary outcome of FRI requiring debridement or amputation was analyzed by multivariable logistic regression considering demographic, injury, and treatment characteristics. RESULTS: 113 patients met eligibility criteria. Median follow-up was 33 months (interquartile range 5-88). 41 patients were initially treated with NPWT, 59 with ABP, and 13 with ABP+NPWT at the initial surgical debridement. 39 (35%) underwent subsequent debridement or amputation for FRI. One amputation occurred in the ABP group for refractory deep surgical site infection (p = 0.630). Initial wound management with an antibiotic bead pouch versus either negative pressure wound therapy alone or negative pressure wound therapy combined with an antibiotic bead pouch was associated with lower odds of debridement or amputation for FRI (ß = -1.08, 95% CI -2.00 to -0.17, p = 0.02). CONCLUSIONS: In our retrospective analysis, antibiotic bead pouch for initial coverage of type IIIB open tibial shaft fractures requiring flap coverage was associated with a lower risk of FRI requiring debridement or amputation than negative pressure wound therapy applied with or without antibiotic beads. A prospective clinical trial is warranted.

Duration of Perioperative Antibiotic Prophylaxis in Open Fractures: A Systematic Review and Critical Appraisal.

Fracture-related infection (FRI) remains a serious complication in open fracture care. Adequate surgical treatment and perioperative antibiotic prophylaxis (PAP) are key factors influencing the outcome. However, data concerning the optimal duration of PAP is scarce. The aim of this systematic review was to provide an overview of current evidence on the association between PAP duration and FRI in open fractures. A comprehensive search on 13 January 2022, in Embase, Medline, Cochrane, Web of Science and Google Scholar revealed six articles. Most studies compared either 1 day versus 5 days of PAP or included a cut-off at 72 h. Although prolonged PAP was not beneficial in the majority of patients, the variety of antibiotic regimens, short follow-up periods and unclear description of outcome parameters were important limitations that were encountered in most studies. This systematic review demonstrates a lack of well-constructed studies investigating the effect of PAP duration on FRI. Based on the available studies, prolonged PAP does not appear to be beneficial in the prevention of FRI in open fractures. However, these results should be interpreted with caution since all included studies had limitations. Future randomized trials are necessary to answer this research question definitively.

Validation of the diagnostic criteria of the consensus definition of fracture-related infection.

BACKGROUND: The recently developed fracture-related infection (FRI) consensus definition, which is based on specific diagnostic criteria, has not been fully validated in clinical studies. We aimed to determine the diagnostic performance of the criteria of the FRI consensus definition and evaluated the effect of the combination of certain suggestive and confirmatory criteria on the diagnostic performance. METHODS: A multicenter, multi-national, retrospective cohort study was performed. Patients were subdivided into an FRI or a control group, according to the treatment they received and the recommendations from a multidisciplinary team ('intention to treat'). Exclusion criteria were patients with an FRI diagnosed outside the study period, patients younger than 18 years of age, patients with pathological fractures or patients with fractures of the skull, cervical, thoracic and lumbar spine. Minimum follow up for all patients was 18 months. RESULTS: Overall, 637 patients underwent revision surgery for suspicion of FRI. Of these, 480 patients were diagnosed with FRI, treated accordingly, and included in the FRI group. The other 157 patients were included in the control group. The presence of at least one confirmatory sign was associated with a sensitivity of 97.5%, a specificity of 100% and a high discriminatory value (AUROC 0.99, p < 0.001). The presence of a clinical confirmatory criterion or, if not present, at least one positive culture was associated with the highest diagnostic performance (sensitivity: 98.6%, specificity: 100%, AUROC: 0.99 (p < 0.001)). In the subgroup of patients without clinical confirmatory signs at presentation, specificities of at least 95% were found for the clinical suggestive signs of fever, wound drainage, local warmth and redness. CONCLUSIONS: The presence of at least one confirmatory criterion identifies the vast majority of patients with an FRI and was associated with an excellent diagnostic discriminatory value. Therefore, our study validates the confirmatory criteria of the FRI consensus definition. Infection is highly likely in case of the presence of a single positive culture with a virulent pathogen. When certain clinical suggestive signs (e.g., wound drainage) are observed (individually or in combination and even without a confirmatory criterion), it is more likely than not, that an infection is present.

Ninety-Day Follow-up Is Inadequate for Diagnosis of Fracture-related Infections in Patients with Open Fractures.

BACKGROUND: Fracture-related infection (FRI) is a challenging complication in musculoskeletal trauma surgery and often complicates the management of open fractures. The CDC currently advocates a surveillance period of 90 days after fracture fixation, but it is unclear what duration of follow-up constitutes adequate surveillance for FRI. Inadequate follow-up will underestimate infections and, in clinical research, will make any interventions studied appear better than they really are, thereby resulting in misleading conclusions. QUESTIONS/PURPOSES: (1) What is the timing of FRI onset in patients with open fractures? (2) What is the proportion of FRIs captured when follow-up is limited to 90 days postoperatively versus when follow-up is extended to 1 year? METHODS: This is a secondary analysis of patient data from a previous retrospective cohort study that investigated whether the duration of perioperative antibiotic prophylaxis was independently associated with FRI in patients with open fractures. Of the 530 eligible patients in the source study, 3% (14) died. Of the remaining 516 patients, 97% (502) patients with 559 long-bone open fractures had 2 years of follow-up constituted the base cohort. Forty-seven fractures in 46 patients were complicated by FRI and were the focus of this secondary analysis. Medical records were reviewed in detail specifically for the current study. Seventy-eight percent (36 of 46) of patients were male, and the mean ± SD age was 42 ± 16 years. The most common mechanism of injury was a motor vehicle accident (63% [29 of 46] of patients), and the tibia was the most involved site (53% [25 of 47] of fractures). The median (interquartile range) time to debridement was 3.0 hours (IQR 2.0 to 4.0). FRIs developed in 3% (7 of 247) of Type I open fractures, 7% (11 of 164) of Type II, 17% (18 of 107) of Type IIIA, 29% (9 of 31) of Type IIIB, and 20% (2 of 10) of Type IIIC open fractures. Each clinic visit of each patient was reviewed, and data about the time of onset of any symptoms and signs suggesting or confirming an FRI, as reported by patients and/or determined by treating surgeons, were recorded. The proportions of FRIs with onset by specific time periods were determined. A Kaplan-Meier survival analysis was performed, and the FRI event rates with 95% confidence intervals were calculated. RESULTS: The median (IQR) time to the onset of FRI was 52 days (IQR 15 to 153). Follow-up of 90 days captured only 64% (30 of 47) of FRIs, whereas follow-up of 1 year captured 89% (42 of 47) of FRIs. The proportion of FRIs with onset within 1 year increased to 95% (42 of 44) in the presence of an already healed fracture. CONCLUSION: Follow-up of 90 days after the management of an open long-bone fracture is inadequate for postoperative surveillance, especially for research purposes. Clinical research on interventions would report results appearing to be much better than they really are, potentially resulting in misleading conclusions. Follow-up of 1 year is preferable because most FRIs will develop before that time, especially when fracture union has occurred. A small percentage of patients may still develop infections beyond the first year after the management of an open fracture. The risk of missing these infections by not extending follow-up beyond 1 year must be balanced against the additional logistical burden. Future prospective multicenter studies and registries with long-term patient follow-up would help clarify this issue.Level of Evidence Level III, diagnostic study.

What is the diagnostic value of the Centers for Disease Control and Prevention criteria for surgical site infection in fracture-related infection?

BACKGROUND: Fracture-related infection (FRI) remains one of the most challenging complications in orthopaedic trauma surgery. An early diagnosis is of paramount importance to guide treatment. The primary aim of this study was to compare the Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of organ/space surgical site infection (SSI) to the recently developed diagnostic criteria of the FRI consensus definition in operatively treated fracture patients. METHODS: This international multicenter retrospective cohort study evaluated 257 patients with 261 infections after operative fracture treatment. All patients included in this study were considered to have an FRI and treated accordingly ('intention to treat'). The minimum follow-up was one year. Infections were scored according to the CDC criteria for organ/space SSI and the diagnostic criteria of the FRI consensus definition. RESULTS: Overall, 130 (49.8%) FRIs were captured when applying the CDC criteria for organ/space SSI, whereas 258 (98.9%) FRIs were captured when applying the FRI consensus criteria. Patients could not be classified as having an infection according to the CDC criteria mainly due to a lack of symptoms within 90 days after the surgical procedure (n = 96; 36.8%) and due to the fact that the surgery was performed at an anatomical localization not listed in the National Healthcare Safety Network (NHSN) operative procedure code mapping (n = 37; 14.2%). CONCLUSION: This study confirms the importance of standardization with respect to the diagnosis of FRI. The results endorse the recently developed FRI consensus definition. When applying these diagnostic criteria, 98.9% of the infections that occured after operative fracture treatment could be captured. The CDC criteria for organ/space SSI captured less than half of the patients with an FRI requiring treatment, and seemed to have less diagnostic value in this patient population.

Surgical management of humeral shaft nonunions. Success of a consistent protocol over 17 years.

INTRODUCTION: Surgical treatment of humeral shaft nonunions is characterized by variability of fixation methods, graft choices, and rates of union and iatrogenic radial nerve palsy. The aim of the current study is to evaluate the union rate of humeral shaft aseptic nonunions and the rate of postoperative complications following a consistent management protocol. PATIENTS AND METHODS: This is a retrospective review of 41 consecutive adult patients (23 female and 18 male with a mean age of 42 years) with aseptic nonunions of the humeral shaft treated by the senior author in our institution over a 17-year period. Nonunions were located in the middle third of the diaphysis in 33 patients, in the distal third in 6, and in the proximal third in 2 patients. Comorbidities were present in 49% of patients and the most common were smoking in 27% and diabetes mellitus in 17% of patients. Patients were treated at an average of 24 months after their injury. Surgical protocol consisted of careful dissection of the radial nerve, debridement of the nonunion site, stable plate fixation and augmentation of local biology. RESULTS: Thirty-eight patients had mean clinical and radiographic follow-up of 9.4 months. All 38 nonunions healed at a mean time of 3.5 months. There were no persistent nonunions and no failures of fixation. None of the 40 patients with an intact radial nerve preoperatively developed any signs of radial nerve compromise after surgery. Complications consisted of one superficial infection (2%) that resolved with oral antibiotics and one deep infection (2%) that required implant removal and debridement. The mean pain score on the visual analog scale was 0.7. Mean elbow range of motion was 125 degrees with a mean extension deficit of 5 degrees and mean flexion of 130 degrees. CONCLUSIONS: Our surgical protocol achieved consistent healing of nonunions of the humeral shaft with a low complication rate and no iatrogenic radial nerve palsy, even in long-standing nonunions in patients with comorbidities.

The influence of duration of infection on outcome of debridement and implant retention in fracture-related infection.

AIMS: The principle strategies of fracture-related infection (FRI) treatment are debridement, antimicrobial therapy, and implant retention (DAIR) or debridement, antimicrobial therapy, and implant removal/exchange. Increasing the period between fracture fixation and FRI revision surgery is believed to be associated with higher failure rates after DAIR. However, a clear time-related cut-off has never been scientifically defined. This systematic review analyzed the influence of the interval between fracture fixation and FRI revision surgery on success rates after DAIR. METHODS: A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed (including MEDLINE), Embase, and Web of Science Core Collection, investigating the outcome after DAIR procedures of long bone FRIs in clinical studies published until January 2020. RESULTS: Six studies, comprising 276 patients, met the inclusion criteria. Data from this review showed that with a short duration of infection (up to three weeks) and under strict preconditions, retention of the implant is associated with high success rates of 86% to 100%. In delayed infections with a fracture fixation-FRI revision surgery interval of three to ten weeks, absence of recurrent infection was reported in 82% to 89%. Data on late FRIs, with a fracture fixation-FRI revision surgery interval of more than ten weeks, are scarce and a success rate of 67% was reported. CONCLUSION: Acute/early FRI, with a short duration of infection, can successfully be treated with DAIR up to ten weeks after osteosynthesis. The limited available data suggest that chronic/late onset FRI treated with DAIR may be associated with a higher rate of recurrence. Successful outcome is dependent on managing all aspects of the infection. Thus, time from fracture fixation is not the only factor that should be considered in treatment planning of FRI. Due to the heterogeneity of the available data, these conclusions have to be interpreted with caution. Cite this article: Bone Joint J 2021;103-B(2):213-221.

Secrets of Success in the Management of Lower Extremity Nonunions.

The key to obtaining healing of nonunions in the lower extremity is to provide a balance of biology and stability. To achieve this goal, the surgeon must understand why the bone did not heal with the initial treatment and change the strategy to improve the outcome. Patients need to be optimized before any proposed surgery. Whether the surgeon uses a certain type of internal or external fixation depends on the location on bone, the type (atrophic versus hypertrophic) of nonunion, the local soft tissue, the element of infection, and the health of the host. The mechanical stability of the fixation, especially in the lower extremity, should be robust and allow some early weight bearing. Early weight bearing stimulates healing, decreases osteoporosis, improves the patient's overall health, and allows early return to function. Diagnosis and management of infected nonunions in the lower extremity is also a major key to a successful outcome in this difficult group of patients.