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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]

Purpose: Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods: FRI patients treated at the University Hospitals of Leuven, Belgium, between January 1st 2015 and November 24th 2019 were evaluated retrospectively. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2-10 weeks) or late-onset (> 10 weeks) FRI. Results: One hundred ninety-one patients with 194 FRIs, most frequently involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram negative bacilli (GNB) (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram positive cocci. Conclusion: This study revealed that in early FRIs, polymicrobial infections and infections including Enterobacterales and enterococcal species were more frequent. A time-based FRI classification is not meaningful to estimate the microbiological epidemiology and cannot be used to guide empiric antibiotic therapy. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Fracture-related infection (FRI) is a feared complication with substantial clinical and economic consequences. The main objective of this study was to compare direct and indirect healthcare costs related to long bone fractures in patients with and without FRI and to assess its impact on the patient's quality of life (QoL).Patients and Methods: Between January 2015 and March 2019, 175 patients with FRI were treated at the University Hospitals Leuven (Belgium). Using a matched-pair analysis, patients with an FRI were matched by age, sex, and fracture location (humeral, femoral, or tibial shaft) to a non-FRI cohort treated during the same time period. Clinical and process-related variables, direct hospital-related healthcare costs, and indirect costs due to absenteeism were compared between the two groups. Furthermore, the patient's QoL was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference.Results: After matched-pair analysis, 15 patients in both the FRI and non-FRI group were included. FRI was associated with direct hospital-related costs being eight times that of non-FRI patients (€ 47,845 [€ 43,072-€ 82,548] vs. € 5,983 [€ 4,519-€ 8,428], p < 0.001). Furthermore, FRI was associated with prolonged absenteeism (340 [340-676] vs. 86 [65-216] days, p = 0.007) and a median indirect cost that was nearly four times that of patients without FRI (€ 77,909 vs. € 19,706). Lastly, FRI patients showed significantly poorer outcomes on both physical function (33 [19-41] vs. 46 [43-44], p < 0.001) and pain interference (24 [13-34] vs. 8 [8-12], p < 0.001) PROMIS scales.Conclusion: Direct hospital-related healthcare costs of FRI are eight times that of non-FRI long bone fractures. Total healthcare costs are mainly driven by hospitalisation costs, wherein FRI is associated with prolonged length of stay. To the best of our knowledge, this study is the first to demonstrate that FRI is also associated with substantial absenteeism, which is almost four times higher compared to non-FRI patients. In addition to this economic impact, FRI significantly deteriorates QoL. Generalizing the outcome of this study should be done cautiously due to the small sample size of 15 patients in both the FRI and non-FRI group after matched-pair analysis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fracture‐related infection (FRI) is a serious complication following musculoskeletal trauma. Accurate diagnosis and appropriate treatment depend on retrieving adequate deep tissue biopsies for bacterial culture. The aim of this cohort study was to compare intraoperative tissue cultures obtained by the Reamer‐Irrigator‐Aspirator system (RIA)‐system against standard tissue cultures obtained during the same surgical procedure. All patients had long bone fractures of the lower limbs and were assigned to the FRI or Control group based on the FRI consensus definition. The FRI group consisted of 24 patients with confirmed FRI and the Control group consisted of 21 patients with aseptic nonunion or chronic pain (in the absence of other suggestive/confirmatory criteria). Standard tissue cultures and cultures harvested by the RIA‐system showed similar results. In the FRI group, standard tissue cultures and RIA cultures revealed relevant pathogens in 67% and 71% of patients, respectively. Furthermore, in four FRI patients, cultures obtained by the RIA‐system revealed additional relevant pathogens that were not found by standard tissue culturing, which contributed to the optimization of the treatment plan. In the Control group, there were no false‐positive RIA culture results. As a proof‐of‐concept, this cohort study showed that the RIA‐system could have a role in the diagnosis of FRI as an adjunct to standard tissue cultures. Since scientific evidence on the added value of the RIA‐system in the management of FRI is currently limited, further research on this topic is required before its routine application in clinical practice. [ABSTRACT FROM AUTHOR]

Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9–30 and MK.R3–15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future. [Display omitted] • In vitro experiments showed good anti-biofilm activity of the phage cocktail in combination with meropenem. • The dual phage and antibiotic loaded hydrogel with microbeads (PA-HM), maintained phage and meropenem activity for at least eight days in vitro. • The use of dual PA-HM increases the tissue levels of bacteriophages, reduces the incidence of phage resistance occurring in the target bacteria and reduces the serum neutralization of phages in vivo. [ABSTRACT FROM AUTHOR]

• FRI of the clavicle is a challenging complication especially in the case of a bone defect. • In our institution, a patient-specific multidisciplinary approach for treatment of clavicular FRI leads to good clinical and radiological outcomes. • Surgical decisions are guided by the bone defect size, soft tissue status and patient demand. • Fracture (construct) stability is one of the most important aspects in the management of FRI of the clavicle. • Healthcare costs are up to 3.5 times higher compared to non-infected surgically treated clavicle fractures. The number of operatively treated clavicle fractures has increased over the past decades. Consequently, this has led to an increase in secondary procedures required to treat complications such as fracture-related infection (FRI). The primary objective of this study was to assess the clinical and functional outcome of patients treated for FRI of the clavicle. The secondary objectives were to evaluate the healthcare costs and propose a standardized protocol for the surgical management of this complication. All patients with a clavicle fracture who underwent open reduction and internal fixation (ORIF) between 1 January 2015 and 1 March 2022 were retrospectively evaluated. This study included patients with an FRI who were diagnosed and treated according to the recommendations of a multidisciplinary team at the University Hospitals Leuven, Belgium. We evaluated 626 patients with 630 clavicle fractures who underwent ORIF. In total, 28 patients were diagnosed with an FRI. Of these, eight (29%) underwent definitive implant removal, five (18%) underwent debridement, antimicrobial treatment and implant retention, and fourteen patients (50%) had their implant exchanged in either a single-stage procedure, a two-stage procedure or after multiple revisions. One patient (3.6%) underwent resection of the clavicle. Twelve patients (43%) underwent autologous bone grafting (tricortical iliac crest bone graft (n = 6), free vascularized fibular graft (n = 5), cancellous bone graft (n = 1)) to reconstruct the bone defect. The median follow-up was 32.3 (P 25 -P 75 : 23.9–51.1) months. Two patients (7.1%) experienced a recurrence of infection. The functional outcome was satisfactory, with 26 out of 28 patients (93%) having full range of motion. The median healthcare cost was € 11.506 (P 25 -P 75 : € 7.953–23.798) per patient. FRI is a serious complication that can occur after the surgical treatment of clavicle fractures. In our opinion, when treated adequately using a multidisciplinary patient-specific approach, the outcome of patients with an FRI of the clavicle is good. The median healthcare costs of these patients are up to 3.5 times higher compared to non-infected operatively treated clavicle fractures. Although not studied individually, we consider factors such as the size of the bone defect, condition of the soft tissue, and patient demand important when it comes to guiding our surgical decision making in cases of osseous defects. [ABSTRACT FROM AUTHOR]