Aims. Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods. Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results. Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion. The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases. Cite this article: Bone Joint Res 2024;13(3):127–135

Aims. The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods. This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results. There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion. The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies. Cite this article: Bone Joint J 2024;106-B(1):77–85

Aims. Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI. Methods. A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months. Results. Recurrent FRI cases consistently exceeded the symptom burden threshold (0.60) in ISR scores at all assessment points. The difference between preoperative-assessed total ISR scores and the 12-month follow-up was not significant in either group, with 0.04 for primary FRI (p = 0.807) and 0.01 for recurrent FRI (p = 0.768). While primary FRI patients showed decreased depression scores post surgery, recurrent FRI cases experienced an increase, reaching a peak at 12 months (1.92 vs 0.94; p < 0.001). Anxiety scores rose for both groups after surgery, notably higher in recurrent FRI cases (1.39 vs 1.02; p < 0.001). Moreover, patients with primary FRI reported lower expectations of returning to normal health at three (1.99 vs 1.11; p < 0.001) and 12 months (2.01 vs 1.33; p = 0.006). Conclusion. The findings demonstrate the significant psychological burden experienced by individuals undergoing treatment for FRI, which is more severe in recurrent FRI. Understanding the psychological dimensions of recurrent FRIs is crucial for comprehensive patient care, and underscores the importance of integrating psychological support into the treatment paradigm for such cases. Cite this article: Bone Jt Open 2024;5(7):621–627

Aims. To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). Materials and Methods. PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. Results. A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. Conclusion. The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis

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

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327

Aims. The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911

Introduction. The management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection. Materials & Methods. A retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union. Results. This approach was associated with successful treatment in 51/55 (93%) patients. Fracture union was achieved in 52/55 (95%) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98%) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13%) pathogens isolated from intra-operative samples demonstrated multi-drug resistance. Conclusions. Initial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93% of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature

Aim. Current guidelines for the diagnosis of prosthetic joint infection (PJI) recommend collecting 4–5 independent tissue specimens, with isolation of indistinguishable organisms from two or more specimens. The same principle has been applied to other orthopaedic device-related infections (DRI) including fracture-related infections. However there are few published data validating this approach in DRI other than PJI. We evaluated the performance of different diagnostic cutoffs and varying numbers of tissue specimens for microbiological sampling in fracture-related infections. Method. We used standard protocols for tissue sample collection and laboratory processing, and a standard clinical definition of fracture-related infection. We explored how tissue culture sensitivity and specificity varied with the number of tissue specimens obtained; and with the number of specimens from which an identical isolate was required (diagnostic cutoff). To model the effect of the number of specimens taken we randomly sampled n specimens from those obtained at each procedure, excluding procedures from which less than n specimens were collected, and calculated sensitivity and specificity based on this sample. For each value of n we repeated this process 100 times to estimate the mean sensitivity and specificity for n specimens. Results. We analysed data for 246 cases of suspected fracture-related infection. 77 (31%) met the clinical definition of infection. A median of 4 independent tissue samples were obtained from each procedure (IQR 4–5). Culture sensitivity was highest and specificity lowest using a diagnostic cutoff of 1 specimen for isolation of an organism; specificity increased at the expense of sensitivity with diagnostic cutoffs of 2 or 3 specimens. Culture sensitivity increased as the number of tissue specimens obtained increased from 1 to 4. Although there was a corresponding decline in specificity with increasing numbers of tissue specimens obtained, this was negligible when a diagnostic cutoff of 2 or 3 specimens with identical organisms was used. Using a cutoff of 2 specimens with identical organisms, obtaining 4 specimens gave a sensitivity of 68% (55–78%) and a specificity of 95% (86–99%). Small numbers prevented meaningful analysis of the diagnostic performance of five or more specimens. Conclusions. These data are analogous to findings in prosthetic joint infections, and suggest similar principles may be applied to tissue sampling and culture interpretation in other orthopaedic DRI including fracture-related infection. A larger study is underway to evaluate the performance of greater numbers of tissue specimens

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. Over a five-year period, FRI patients treated at the University Hospitals of Leuven, Belgium, were retrospectively included. 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, mainly 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 (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. The high frequency of polymicrobial infections, including Enterobacterales and enterococci, should be considered when choosing an empirical regimen, especially for early FRI. However, since antibiotic stewardship is the cornerstone of good antibiotic practice, overuse and misuse of broad-spectrum empiric therapy should be avoided at all costs. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy

Aim. To classify Fracture-related Infection (FRI) allowing comparison of clinical studies and to guide decision-making around the main surgical treatment concepts. Method. An international group of FRI experts met in Lisbon, June 2022 and proposed a new FRI classification. A core group met during the EBJIS Meeting in Graz, 2022 and on-line, to determine the preconditions, purpose, primary factors for inclusion, format and the detailed description of the elements of an FRI Classification. Results. Historically, FRI was classified by time from injury alone (early, delayed or late). Time produces pathophysiological changes which affect the bone, the soft-tissues and the patient general health, over a continuum. No definitive cut-off is therefore possible. Also, in several studies, time was not identified as an independent predictor of outcome. The most important primary factors were characteristics of the fracture (F), relevant systemic co-morbidities of the patient (R) and impairment of the soft-tissue envelope (I). These factors determine FRI severity, choice of treatment method and are predictors of outcome. For the fracture (F), the state of healing, the potential for bone healing and the presence or absence of a bone defect are critical factors. Co-morbidities are listed and the degree of end-organ damage is important (R). The ability to close the wound directly or the need for soft tissue reconstruction determines the impairment of the soft tissue component (I). Hence the FRI Classification was designed. The final proposal of the FRI Classification is presented here. The new classification has five stages; from simple cases of infected healed fractures, in healthy individuals with good soft tissues (Stage 1), through unhealed fractures with variable potential for bone healing (Stages 2, 3 or 4) to Stage 5, with no limb-sparing or reconstructive options. For instance, the need for a free flap (I4), over a well-healed fracture (F1), in a patient with 2 co-morbidities (R2) gives a classification of F1R2I4 for that patient. Conclusions. This novel approach to FRI classification builds on previous work in osteomyelitis, PJI and chronic medical conditions. It focusses attention on the elements of the disease which need treatment. It now requires validation in large patient cohorts. On behalf of the FRI Classification Consensus Group

Aim. 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. Method. 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. Results. 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. Conclusion. FRI is a serious complication that can occur after the surgical treatment of clavicle fractures. Overall, the outcome of patients treated for FRI of the clavicle is good, when management of this complication is performed by using a multidisciplinary team approach. The median healthcare costs of these patients are up to 3.5 times higher compared to non-infected operatively treated clavicle fractures. Expert opinion considers factors such as the size of the bone defect, the condition of the soft tissue, and patient demand to guide surgical decision making

Aim. Ankle fracture surgery comes with a risk of fracture-related infection (FRI). Identifying risk factors are important in preoperative planning, in management of patients, and for information to the individual patient about their risk of complications. In addition, modifiable factors can be addressed prior to surgery. The aim of the current paper was to identify risk factors for FRI in patients operated for ankle fractures. Method. A cohort of 1004 patients surgically treated for ankle fractures at Haukeland University hospital in the period of 2015–2019 was studied retrospectively. Patient charts and radiographs were assessed for the diagnosis of FRI. Binary logistic regression was used in analyses of risk factors. Regression coefficients were used to calculate the probability for FRI based on the patients’ age and presence of one or more risk factors. Results. FRI was confirmed in 87 (9%) of 1004 patients. Higher age at operation (p < 0.001), congestive heart failure (CHF), p = 0.006), peripheral artery disease (PAD, p = 0.001), and current smoking (p = .006) were identified as risk factors for FRI. PAD and CHF were the risk factors displaying the strongest association with FRI with an adjusted odds ratio of 4.2 (95% CI 1.8–10.1) and 4.7 (95% CI 1.6–14.1) respectively. Conclusions. The prevalence of FRI was 9% after surgical treatment of ankle fractures. The combination of risk factors found in this study demonstrate the need for a thorough, multidisciplinary, and careful approach when faced with an elderly or frail patient with an ankle fracture. The results of this study help the treating surgeons to inform their patients of the risk of FRI prior to ankle fracture surgery

Aims. With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). Methods. A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10. 4. colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Results. Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. Conclusion. In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49–60

Aims. This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis. Results. Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966–72

This study aimed to investigate the outcomes of open tibia shaft fractures at a level one trauma center in a developing world setting. Specific objectives were to determine the association of time delay to antibiotic administration, surgical debridement, definitive skeletal stabilisation and soft tissue reconstruction, and the development of fracture-related infection (FRI). A retrospective cohort study included all adult patients with open tibia shaft fractures from July 2014 to June 2016 and January 2018 to December 2019. Patients who were skeletally immature at the time of injury, those with pathological fractures and who did not complete follow-up of at least three months were excluded. Patients were identified from hospital records. Data was captured in Microsoft Excel and analysed using STATISTICA. A Chi-squared was used to detect significant differences between groups. No association between infection and antibiotic administration was observed when patients were treated within or after 3 hours (p=0.625) or if patients had their first surgical debridement in theatre before or after 24 hours (p=0.259). Patients who waited more than five days for definitive skeletal fixation or soft tissue reconstruction had a significant increase in FRI (OR 4.7, 95% CI 2.0 – 10.9 and OR 4.7, 95% CI 2.0 – 11.0, respectively). Patients who underwent more than two formal debridements had a higher risk of developing FRI (OR 15.6, 95% CI 5.8 – 41.6). Whilst administration of antibiotics within 3 hours of presentation to the emergency unit had no impact on the development of FRI, time delays in managing open tibia shaft fractures are associated with an increased risk for FRI. Definitive soft tissue reconstruction and skeletal stabilization should not be delayed for more than five days

Background. Fracture-related infection (FRI) is treated by adequate debridement, lavage, fracture stabilization (if indicated), adequate soft tissue coverage and systemic antimicrobial therapy. Additional administration of local antibiotics (LA), placed directly in the surgical field, is thought to be beneficial for successful eradication of infection. Aims. 1) To evaluate the effect of local antibiotics on outcome in patients with FRI. 2) To evaluate whether bacterial resistance to the implanted local antibiotics influences its efficacy. Methods. A multinational cross-sectional study was performed in patients with FRI, diagnosed according to the FRI consensus definition, between January 2015 and December 2019. Patients who underwent surgical treatment for FRI at all time points after injury were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse Probability for Treatment Weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of LA and recurrence rate of FRI at 12 months, 24 months and final follow-up. Results. Overall, 433 FRIs in 429 patients were included. A total of 251 (58.0%) cases were treated with LA. Gentamicin was the most frequently used LA (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received LA and in 34/182 (18.7%) patients who did not. The use of LA reduced the recurrence rate of FRI at 12 months (HR: 0.69; 95% CI [0.24–1.96]) and 24 months (HR: 0.55; 95% CI [0.22–1.35]). Resistance of cultured microorganisms to the LA was not associated with a higher risk of recurrence of FRI (HR: 0.75, 95% CI [0.32–1.74]). Conclusion. The application of LA in treatment of FRI is likely to reduce the risk of recurrence of FRI as the risk reduction was consistent and clinically relevant but it did not reach statistical significance. High local antibiotic concentrations eradicate most pathogens regardless of susceptibility test results

Aim. This study investigated the management and clinical outcomes of patients treated for confirmed fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. Method. All patients with FRI, confirmed by the FRI Consensus Definition. 1. and treated surgically, were included. Data were collected on patient characteristics, time from injury to FRI surgery, soft tissue reconstruction, type of stabilization and use of local antibiotics. All patients were followed up for at least one year. The rates of eradication of infection and union were assessed. The associations between treatment methods, time from injury and outcomes were determined. Results. 433 FRIs were treated in patients with mean age 49.7 years (range 14–84). FRI affected the tibia in 226(52.2%), femur in 94(21.7%), pelvis in 26(6%), humerus in 20(4.6%) and foot bones in 19(4.4%). Patients were followed up for a mean of 26 months (range 12–72). Overall, eradication of infection was successful in 86.4% of cases and 86% of unhealed infected fractures were healed at final review. 3.3% required amputation. Successful outcome was not dependent on age, or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p=0.52). Method of stabilization had a major affect on outcome. Debridement and retention of a stable infected implant (DAIR) had a failure rate of 22.3%, implant exchange (to new internal fixation) 16.7%, conversion to external fixation 7.4%. DAIR was significantly worse than conversion to external fixation (p=0.01). There was no effect of the time from injury on the outcome of DAIR or any other fixation method. The use of a free flap in the tibia improved the success rate from 80.4% to 92.1% (p=0.044). Outcome was adversely affected by use of a split skin graft alone in soft tissue reconstruction (44% failure) (p=0.006). The use of local antibiotics reduced the recurrence rate from 18.3% to 10.3% (p=0.022). Conclusions. This study is the first to consider outcome for all FRIs, at all-time points, with all treatment modalities. Treatment was mostly successful but may be improved with better directed use of free flaps, local antibiotics, and limitation of DAIR. The results suggest that the division of FRIs into categories based on time from injury, may not be helpful with modern treatment

Aim. This study investigated the effect of the choice of antibiotic regime on outcome of patients treated for fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. Method. All patients with FRI, confirmed by the FRI Consensus Definition. 1. and treated surgically, were included. Data were collected on patient characteristics, microbial cultures, antibiograms, empiric and definitive systemic antibiotic regimes and local antibiotic use. All patients were followed up for at least one year. The primary outcome was eradication of infection. The chosen antibiotic regimes were compared to the recent guidelines from the FRI Consensus Group. 2. , to assess the correlation with outcome. Results. 433 FRIs were treated in patients with mean age 49.7 years (range 14–84). Patients were followed up for a mean of 26 months (range 12–72). A microbiological diagnosis was obtained in 353 patients (18.5% culture negative rate), with 46% monomicrobial and 35.5% polymicrobial. Staph aureus was present in 51.3% of monomicrobial and 55.2% of polymicrobial infections. Negative cultures were much less likely in FRI within 10 weeks of injury (p=0.00001). Treatment failure with recurrent infection occurred in 13.6% of patients. Failure was more likely in culture positive cases (Polymicrobial; p=0.016, monomicrobial 0.039). Definitive antibiotic regimes were fully compliant with the FRI Guideline in 107 cases (24.7%). In 294 cases (68%) antibiotic regimes outside the guidelines were used. Non-compliance was often due to differences in recommended dosing or overtreatment with extra antimicrobials. 32 cases (7.4%) could not be assessed against the FRI Guidelines as the organisms or regimes were not represented in the guide. Failure rate with FRI Guideline compliant regimes was 12.1% and with non-compliant, 13.2% (p=0.87). Failure in unclassifiable cases was 21.9%. The use of local antibiotics reduced the recurrence rate from 18.3% without local antibiotics to 10.3% with local antibiotics (p=0.022). Conclusions. This study demonstrated that there can be considerable variability in the choice of antimicrobial regimes in FRI. Some deviations from the FRI Guideline did not result in poorer outcomes. These smaller differences in antimicrobial choice may not be major determinants of outcome

Aim. By gaining insight into the Quality of Life (QoL) status and occurrence of complications, critical facets in the care for patients with Fracture-Related Infection (FRI) can be mitigated and measures can be taken to improve their outcome. Therefore, the aims of this study were to 1) determine the QoL in FRI patients in comparison to non-FRI patients and 2) describe the occurrence of complications in both FRI and non-FRI patients. Method. An ambidirectional cohort study was conducted in a level-1 trauma centre between January 1st 2016 and November 1st 2021. All patients who underwent surgical stabilisation of a long bone fracture were eligible for inclusion. Patients with an Injury Severity Score (ISS) ≥16 or incomplete follow-up were excluded. QoL was assessed through the use of five-level EuroQol five-dimension (EQ-5D-5L) questionnaires twelve months post-injury. Results. A total of 134 patients were included, of whom 38 (28%) FRI patients and 96 (72%) non-FRI patients. In comparison to non-FRI patients, FRI patients scored significantly worse on the QoL assessment regarding the index value (p=0.012) and the domains mobility (p<0.001), usual activities (p=0.010) and pain/discomfort (p=0.009). During the median follow-up of 14.5 months (interquartile range (IQR) 9.5–26.5), 25 FRI patients developed a total of 49 distinctive complications besides FRI. The complications nonunion (18%, n=9/49), infection other than FRI (e.g. line infection, urinary tract infection, pneumonia) (18%, n=9/49) and implant failure (14%, n=7/49) were the most frequently described in the FRI group. Conclusions. Patients who suffered from an FRI have a decreased QoL in comparison to those without an FRI. Moreover, patients with an FRI have a higher rate of additional complications. These findings can help in patient counselling regarding the potential physical and mental consequences of having a complicated course of recovery due to an infection

Aim. Fracture-related infection (FRI) is a severe post-traumatic complication which can be accompanied with a soft-tissue defect or an avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative since a vital soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of our study was to analyse plastic surgical aspects in the management of FRIs, including the type and outcome of soft-tissue reconstruction (STR), and to investigate the long-term outcome of FRI after STR. Method. Patients with a lower leg FRI requiring STR that were treated from 2010 to 2018 at our center were included in this retrospective analysis. STR involved the use of local, pedicled and free flaps. The primary outcome was the success rate of STR, and the secondary outcome was long-term fracture consolidation and cure of infection. Results. Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR. Muscle flaps were applied in 38, fascio-cutaneous flaps in 19 and a composite osteo-cutaneous flap in one case. All patients underwent successful STR (primary STR in 51/58 patients, 7/58 patients needed secondary STR). A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p=0.011). Patients with free-flap STR developed significantly more severe complications and needed more surgical interventions (Clavien-Dindo ≥IIIa; p=0.001). Out of the 43 patients that completed long-term follow-up (mean 24 months), fracture consolidation was achieved in 32 and infection eradication in 31. Polymicrobial infection was a significant risk factor for fracture non-union (p=0.002). American Society of Anesthesiologists (ASA) classification of 3 or higher (p=0.040) was a risk factor for persistence or recurrence of infection. Conclusions. In our population, 58/145 patients with FRI required STR. STR was successful in all patients eventually, in 7/58 patients secondary STR was necessary. Therefore, STR should be sought even if primary STR fails. Despite successful STR, the long-term composite outcome showed a high rate of failed fracture consolidation and failed eradication of infection, which was independent of primary STR failure

Aim. The aim was to investigate the value of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results and histological analysis in 156 surgically treated non-unions were used to stratify the likelihood of associated infection. There were 64 confirmed infected non-unions (≥1 confirmatory criteria; pus, sinus and bacterial growth in ≥2 samples), 66 aseptic non-unions (no confirmatory criteria) and 26 possibly infected (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorphs (NPs) counts per high power field (HPF) and compared to the established diagnosis. Results. Assuming a cut-off of >5NPs/HPF for positive histological diagnosis, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of any NPs/HPF (>0) for negative histological diagnosis there was a sensitivity of 98% and a specificity of 85% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of >5 NPs/HPF has a positive predictive value of 100%, while the complete absence of any NPs is almost always indicative of an aseptic non-union (negative predictive value: 98%)

Aim. Staphylococcus aureus is the leading pathogen in fracture-related infection (FRI). Virulence factors vary between different strains, which may have a decisive influence on the course of infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of S. aureus isolates from FRI identified a low- and high-virulent strain. These findings correlated with the acute course of FRI induced by the high-virulent pathogen, whereas the low-virulent strain caused a chronic FRI in its human host. However, the role of bacterial virulence in FRI is not completely understood. Therefore, the present study aimed to compare the identified high- and low-virulent S. aureus isolates in a murine FRI model. Method. Skeletally mature C57Bl/6N mice received a femoral osteotomy stabilized by titanium locking plates. FRI was established by inoculation of either high-virulent S. aureus EDCC 5458 or low-virulent S. aureus EDCC 5464 in the fracture gap. Mice were euthanized 4 and 14 days after surgery, respectively. Severity and progression of infection were assessed in terms of clinical presentation, quantitative bacteriology, semiquantitative histopathologic evaluation, and serum cytokine profile. Results. Quantitative bacteriological results 4 days after surgery revealed a higher bacterial load in soft tissue samples in high-virulent infected animals (p =0.026). Mice infected with the high-virulent strain also displayed higher rates of organ dissemination (24/36 organs in high-virulent, versus 5/36 organs in low-virulent infected animals; p <0.0001). In the histopathological assessment, bacterial agglomerations at the fracture ends were present to a greater extent in the high-virulent cohort and barely detectable in low-virulent infected mice. In both cohorts, no bone healing was observed after 4 days. On day 14, bone healing at the fracture site was visible in low-virulent infected animals, whereas callus formation was observed in only one animal from the high-virulent infected cohort. Furthermore, osteonecrosis and osteolysis were increased in high-virulent infected animals. Regarding serum cytokines, innate immune markers were elevated in both groups at day 4. By day 14, a more pronounced proinflammatory response indicated by increased serum cytokine levels of IFN-γ, IL-1β, and IL-6 was observed in high-virulent infected animals. Conclusions. The present study demonstrated distinct bacteriological and histopathological differences between two different virulent S. aureus strains previously shown to have different courses in human patients. While host physiology is often considered to have a major impact on the course of FRI, this study highlights the critical influence of the invading pathogen and its virulence characteristics

Aim. Surgical treatment of ankle fractures comes with a substantial risk of complications, including infection. An unambiguously definition of fracture-related infections (FRI) has been missing. Recently, FRI has been defined by a consensus group with a diagnostic algorithm containing suggestive and confirmatory criteria. The aim of the current study was to report the prevalence of FRI in patients operated for ankle fractures and to assess the applicability of the diagnostic algorithm from the consensus group. Method. Records of all patients with surgically treated ankle fractures from 2015 to 2019 were retrospectively reviewed for signs of postoperative infections. Patients with suspected infection were stratified according to confirmatory or suggestive criteria of FRI. Rate of FRI among patients with confirmatory and suggestive criteria were calculated. Results. Suspected infection was found in 104 (10%) out of 1004 patients. Among those patients, confirmatory criteria were met in 76/104 (73%) patients and suggestive criteria were met in 28/104 (27%) at first evaluation. Patients with clinical confirmatory criteria (N= 76) were diagnosed with FRI. Patients with suggestive criteria were further examined with either bacterial sampling at the outpatient clinic, revision surgery including bacterial sampling, or a wait-and-see approach. Eleven (39%) of the 28 patients had positive cultures and were therefore diagnosed as having FRI at second evaluation. In total 87 (9%) patients were diagnosed with FRI according to the consensus definition. Only 73 (70%) of the 104 patients with suspected FRI had adequate bacterial sampling. Conclusions. The prevalence of FRI, applying the FRI-consensus criteria, for patients with surgically treated ankle fractures was 9%. Twenty-two percent of patients who met the confirmatory criteria had negative bacterial cultures. The current study shows that we did not have a systematic approach to patients with suspected FRI as recommended by the consensus group. A systematic approach to adequate bacterial sampling when FRI is suspected is paramount. The consensus definition of FRI and its diagnostic algorithm facilitates such an approach

Aim. Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA. Method. Two evolved bacteriophages (MRSA-R14 and COL-R23) with improved antibiofilm activity against a clinical isolate (MRSA3) were tested in combination with vancomycin and a carboxymethylcellulose (CMC) hydrogel in vitro and in vivo. MRSA3 bacterial biofilms were formed on sterile 4 mm sintered porous glass beads at 37 °C for 24 h. Biofilms were exposed to i-phage cocktail (10. 7. PFU/ml), ii-vancomycin at concentrations of 0.5, 1, 10 and 100 times the MIC, or iii-combination of phage cocktail and vancomycin. Recovered biofilm cells, were quantified by colony counting. The stability and release profiles of phage cocktail and vancomycin in co-delivery hydrogel were assessed in vitro for 8 days and 72 hrs, respectively, and subsequently tested in the treatment of 5-day-old MRSA3 infection of a femoral plate osteotomy in mice. Results. In vitro: The cocktail of evolved phages (10. 7. PFU/ml, 1:1) combined with 0.5 MIC vancomycin achieved 99.72% reduction in MRSA3 biofilm in vitro compared to the growth control. This combination was stable in the co-delivery hydrogel over 8 days. The release profile showed that 57% of phages and 80% of vancomycin were released after 72hrs, which was identical to the performance for gels loaded with phage or antibiotic alone. In the in vivo study, the bacterial load from animals that received co-delivery hydrogel and systemic vancomycin was significantly reduced compared to controls, animals that received systemic vancomycin and animals that received co-delivery hydrogel alone (p<0.05). Conclusions. Our study demonstrates the potential of using evolved phages in combination with vancomycin and hydrogel delivery systems for the treatment of MRSA-related infections. Further research in this area may lead to the development of specific therapies for biofilm-related infection

Aim. The time to onset of symptoms after fracture fixation is still commonly used to classify fracture-related infections (FRI). Early infections (<2 weeks) can often be treated with debridement, systemic antibiotics, irrigation, and implant preservation (DAIR). Late infections (>10 weeks) typically require implant removal as mature, antibiotic-tolerant biofilms have formed. However, the recommendations for delayed infections (2–10 weeks) are not clearly defined. Here, infection healing and bone healing in early and delayed FRI is investigated in a rabbit model with a standardized DAIR procedure. Method. Staphylococcus aureus was inoculated into 17 rabbits after plate osteosynthesis in a humerus osteotomy. The infection developed either one week (early group, n=6) or four weeks (delayed group, n=6) before a standardized DAIR procedure and microbiological analysis were performed. Systemic antibiotics were administered for six weeks (two weeks: Nafcillin+Rifampin, four weeks: Levofloxacin+Rifampin). A control group (n=5) also underwent a revision operation (debridement and irrigation) after four weeks, but received no antibiotic treatment. Rabbits were euthanized seven weeks after the revision operation. Bone healing was assessed using a modified radiographic union score for tibial fractures (mRUST). After euthanasia, a quantitative microbiological examination of the entire humerus, adjacent soft tissues, and implants was performed. Results. All animals were infected at the time of revision surgery, with the bacterial load in the early group (especially in soft tissues) being greater than in the delayed group and control group. This indicates infiltration of bacteria into areas that are more difficult to reach after four weeks of debridement. The infection was eradicated in all animals in both the early and delayed groups at euthanasia, but not in the control group (CFU median (IQR): 2.1×10. 7. (1.3×10. 7. -2.6×10. 7. ). The osteotomy healed in the early group, while bone healing was significantly impaired in both the delayed group and control group (mRUST median (IQR): early group: 16 (14–16), delayed group: 7.5 (6–10), control: 7 (5.5–9); early vs. delayed: p=0.0411, early vs. control p=0.0065). Conclusion. The maturation of the infection between the first and fourth week does not affect the success of infection eradication in this rabbit FRI model. However, bone healing appears to be impaired with increasing duration of infection

Aims. Fracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure. Methods. This multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate. Results. A total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]). Conclusions. Although the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI

Aim. Duration of perioperative antimicrobial prophylaxis (PAP) remains controversial in prevention of fracture-related infection (FRI) – with rates up to 30% - in open fracture (OF) management. Objectives were to investigate the impact of the PAP duration exclusively in or related to long bone OF trauma patients and the influence of augmented renal clearance (ARC), a known phenomenon in trauma patients, as PAP consists of predominantly renally eliminated antibiotics. Method. Trauma patients with operatively treated OF, admitted between January 2003 and January 2017 at the University Hospitals Leuven, were retrospectively evaluated. FRI was defined following the criteria of the consensus definition of FRI. A logistic regression model was conducted with FRI as outcome. Results were considered statistically significant when p< 0.05. Results. Forty (8%) from the 502 patients developed a FRI, with 20% FRIs in Gustilo-Anderson (GA) III OFs. Higher GA grade and polytrauma were independently associated with the occurrence of FRI. The heterogeneity in OF management, especially with regard to the applied PAP regimens and duration, was striking and consequently hampering the investigation on the impact of PAP duration. To overcome this issue, a subgroup analysis was performed in patients treated with the two PAP regimens as defined in the hospitals' guidelines – i.e. cefazolin, with metronidazole and tobramycine when extensive contamination was present -, revealing flap coverage and relative duration of augmented renal ARC as independently associated factors. Conclusions. For the first time, a definition based on diagnostic criteria was used to objectively include patients with a FRI. In order to support clinicians in establishing strategies to prevent FRI in long bone OFs, further prospective large randomized controlled trials with clearly predefined PAP regimens are needed to provide reliable recommendations regarding the impact of duration of PAP and ARC

Aim. Focused high energy extracorporeal shockwave therapy (fhESWT) is used to support fracture healing in non-union cases and has been shown to have antibacterial effects. We trialed fhESWT as an adjunct to conventional treatment in a clinically relevant rabbit model of fracture related infection. Method. A complete humeral osteotomy was performed in 31 rabbits and fixed with a 7-hole-LCP. A fracture-related infection (FRI) was established with Staphylococcus aureus. After two weeks, a revision surgery was performed with debridement, irrigation and implant retention. Rabbits then received: no further treatment (controls); shockwaves (at day 2 and 6 after revision, 4'000 Impulses each time with 23kV); systemic antibiotics (rifampin and nafcillin) over one week in weight adjusted dosages; or the combination of antibiotics and shockwaves. Treatments were applied over one week. Blood cultures were taken before and after shockwave sessions. After an additional week without treatment, rabbits were euthanized, and quantitative bacteriology was performed on implants and tissues to determine infection burden. Indicator organs (brain, heart, liver, lungs, kidneys and spleen) were cultured to assess possible bacteraemia due to fhESWT. Results. All rabbits were infected at revision surgery as determined by bacteriological culture of debrided materials. fhESWT in combination with antibiotic treatment lowered the bacterial burden at euthanasia hundredfold compared to antibiotic treatment alone in all samples (p=0.38). This effect was most prevalent for the implant sample (p=0.08). No significant effect was seen for fhESWT alone compared to untreated controls. No signs of bacteraemia occurred. Conclusions. The additon of systemic antibiotics had the biggest effect on reduction of bacteria. Although further lowering the bacterial burden in our model the effect of fhESWT as an adjunct was not big enough to be statistically secured in this in vivo rabbit model. In certain difficult-to-treat infections the addition of fhESWT might be beneficial. The method appears to be safe in this model of acute FRI as no signs of bacteremia occurred despite the high energy and impulse number. Further investigations are needed to identify the correct indication

Aim. The aim of this systematic review was to determine 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. Method. We performed a systematic literature search on treatment and outcome of critical-sized bone defects in FRI. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, bone transport, and bone transport combined with local antibiotics. Studies describing bone defects of 1 cm or greater were included. 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 1,530 patients, of which the tibia was affected in 82%. The 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 lasted 51 months (range 6–126). Four studies (8%) described treatment using vascularized grafts, 18 (36%) cancellous grafts, 8 (16%) the induced membrane technique, and 20 (40%) bone transport. A total of 1063 grafts were used of which 30% were vascularized and 60% were cancellous bone. 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). Conclusions. This is the first extensive review of bone defect treatment protocols in chronic/late-onset FRI. Overall published work showed a high success rate of 94% and low amputation rate of only 3%. However, data did not allow a reliable comparison across treatments. The results should thus 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 in order to improve reliability of future studies

Aim. Fracture-related infection (FRI) is a serious complication after trauma. More often resistant micro-organisms are cultured. Gentamicin covers a wide variety of causative agents for FRI. A bio-absorbable antibiotic carrier, Cerament-G®, combines dead space management with local release of gentamicin in a one-stage approach. The achieved tissue concentrations of locally applied antibiotics are 4–8 thousand times higher than after systemic administration. Does Cerament-G® have antimicrobial activity towards bacteria that are not susceptible to systemic gentamicin administration. Method. The four most often cultured bacterial species found in FRI were used; Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae. For each species, four different isolates were obtained, each with a different susceptibility for gentamicin. This susceptibility, expressed in the minimal inhibitory concentration (MIC), varied from completely susceptible (MIC 0,064 mg/L – 4mg/L), minimal resistance (4mg/L – 16mg/L), moderate resistance (8 mg/L – 96 mg/L) to high resistance (24 mg/L - >1024 mg/L), depending on each different organism. Antimicrobial activity of Cerament-G. ®. was determent by a Kirby-Bauer test, according to the EUCAST disc protocol. Each test was done in five-fold for each of the 16 cultured isolates, four of each species. The zone of inhibition (ZOI), obtained by the test, was compared between each bacterial isolate and within each of the four separate species. Results. Cerament-G. ®. shows antimicrobial activity against S. aureus, S. epidermidis, P. aeruginosa and E. cloacae. ZOI-values varied from 11 to 44 mm. It was negatively correlated with the MIC; the higher the MIC, the less the antimicrobial effect of Cerament-G. ®. Between bacterial isolates with the same MIC, within the same species, there was no significant difference in ZOI between the five-fold repetitions of the test, indicating an accurate test. The ZOI of the different bacterial isolates (with different MIC's), belonging to the same bacterial species, differed significantly. Of all 16 isolates, only the S. aureus with a MIC of >1024 mg/L did not show antimicrobial activity of Cerament-G. ®. ; ZOI =0mm. Conclusions. This study shows that Cerament-G. ®. has antimicrobial activity against bacterial isolates, resistant to gentamicin when systemically treated. This confirms that the cut-off point for systemic application is not very useful for the local use of Cerament-G. ®. and emphasizes the need for optimization and change of current antibiotic protocols to increase the durability and sustainability of antibiotic FRI treatment

Aim. Negative-pressure wound therapy (NPWT) is often propagated as treatment option for fracture-related infection (FRI). After surgical debridement and repeated NPWT dressing changes, the wounds are often closed by free flaps. Sometimes even healing by secondary intention seems an alternative. Recently, concerns have been raised on the long-term use of NPWT as it could be related to bacterial overgrowth and possible re-infection. The purpose of this study was to conduct a retrospective evaluation of the influence of long-term NPWT on tissue culture results and outcome in FRI patients. Method. Between January 1. st. , 2015 and December 31st, 2018, a total of 852 patients were treated with NPWT for different indications on the Department of Trauma Surgery. Inclusion criteria for this study were patients with a closed fracture, stabilized with osteosynthetic fixation and complicated with a confirmed FRI according to the FRI consensus definition. Patients were included when they received at least three NPWT dressing changes in the operating room. Exclusion criteria were patients younger than 18 years, or the absence of cultures results from dressing changes. Results. During the study period 23 patients met the inclusion criteria. According to the tripartite classification of Willenegger and Roth, one patient had an early, 14 a delayed and 8 patients a late onset FRI. Overall, 139 NPWT dressing applications were performed, with an average amount of six per patient. In 14 patients (61%) and 57 dressing changes (41%), at least 2 tissue cultures showed the same pathogen or at least one, in case of highly virulent organisms (e.g. S. aureus) during a single dressing exchange. Coagulase-negative staphylococci were present in 33% of the cases, followed by Enterococcus spp. (21%), S. aureus (16%), non-fermentative gram negative bacilli (14%) and Enterobacteriaceae (7%). Furthermore, 17 exchanges showed polymicrobial growth. Five patients had repeatedly significant growth of the same pathogen despite adequate antimicrobial therapy, within this group one patient was immunocompromised. Conclusions. In a large amount of patients (61%), a significant number of positive culture results could be acquired, even in the presence of adequate local and systemic antimicrobial therapy. The clinical relevance of these results remains unclear. This said, it seems important to limit the duration of NPWT as prolonged treatment could increase bacterial overgrowth and possible (re-)infection. Therefore, a rapid definitive soft tissue coverage should be encouraged. Future larger prospective clinical trials are required

Introduction

Fracture related infection (FRI) is a challenging complication to manage in an orthoplastic setting. Consensus guidelines have been created to standardise the diagnosis of FRI and comprise confirmatory and suggestive criteria. In this study, the aim is to assess the diagnostic criteria and management of FRI with a particular focus on soft tissue reconstruction.

Introduction

A greater emphasis has been placed on fracture related infection (FRI) orthopaedic practice as a separate entity in recent years. Since the publication of the FRI consensus definition and guidelines, there has been an increase in the published literature on the topic and a move towards considering FRI as separate from general orthopaedic practice and as work that requires a more specialist approach. The aim of this study was to audit current FRI practice in the UK.

Aim

Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection.

Aim

Chronic bone infections and infected fractures are often treated with excision of the dead bone and implantation of biomaterials which elute antibiotics. Gentamicin has been a preferred drug for local delivery, but this could induce renal dysfunction due to systemic toxicity. This is a particular concern in patients with pre-existing chronic renal disease treated with new antibiotic carriers which achieve very high peak levels of gentamicin in the first few days after surgery.

Introduction

The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity. We aim to establish the risk of renal injury with local delivery in a ceramic carrier.

Aim

Fracture related infection (FRI) remains a challenging diagnosis in orthopedic and trauma surgery. In addition to clinical signs and imaging, serum inflammatory markers are often used to estimate the probability of FRI. To what extent serum inflammatory markers can be used to rule out and diagnose FRI remains unclear. The aim of this systematic review was to assess the diagnostic value of the serum inflammatory markers C-reactive protein (CRP), leukocyte count (LC) and erythrocyte sedimentation rate (ESR) in suspected fracture related infection.

Aims. This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes?. Methods. Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors. Results. Union failure occured in 0.89% (95% confidence interval (CI) 0.83 to 0.95) after head/neck fracturs, in 0.92% (95% CI 0.84 to 1.01) after intertrochanteric fracture and in 1.99% (95% CI 1.69 to 2.33) after subtrochanteric fractures within 24 months. A fracture-related infection was more likely to occur after subtrochanteric fractures than after head/neck fractures (1.64% vs 1.59%, hazard ratio (HR) 1.01 (95% CI 0.87 to 1.17); p < 0.001) as well as after intertrochanteric fractures (1.64% vs 1.13%, HR 1.31 (95% CI 1.12 to 1.52); p < 0.001). Anticoagulant use, cerebrovascular disease, a concomitant fracture, diabetes mellitus, hypertension, obesity, open fracture, and rheumatoid disease was identified as risk factors. Mechanical complications after 24 months were most common after head/neck fractures with 3.52% (95% CI 3.41 to 3.64; currently at risk: 48,282). Conclusion. The determination of complication rates for each fracture type can be useful for informed patient-clinician communication. Risk factors for complications could be identified for distinct proximal femur fractures in elderly patients, which are accessible for therapeutical treatment in the management. Cite this article: Bone Jt Open 2023;4(10):801–807

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Objectives. The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. Methods. A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”. Results. The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. Conclusion. Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing. Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304–312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2

Objectives. As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. Methods. A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis. Results. In total, eight studies which included 2738 patients were eligible for quantitative synthesis. The effect of antibiotic-loaded poly(methyl methacrylate) beads was investigated by six of these studies, and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.6%; 91/1986) than in the control group receiving standard systemic prophylaxis alone (16.5%; 124/752) (p < 0.001) (odds ratio 0.30; 95% confidence interval 0.22 to 0.40). Conclusion. This meta-analysis suggests a risk reduction in FRI of 11.9% if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity, and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution. Cite this article: M. Morgenstern, A. Vallejo, M. A. McNally, T. F. Moriarty, J. Y. Ferguson, S. Nijs, WJ. Metsemakers. Bone Joint Res 2018;7:447–456. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

The June 2024 Trauma Roundup. 360. looks at: Skin antisepsis before surgical fixation of limb fractures; Comparative analysis of intramedullary nail versus plate fixation for fibula fracture in supination external rotation type IV ankle injury; Early weightbearing versus late weightbearing after intramedullary nailing for distal femoral fracture (AO/OTA 33) in elderly patients: a multicentre propensity-matched study; Long-term outcomes with spinal versus general anaesthesia for hip fracture surgery; Operative versus nonoperative management of unstable medial malleolus fractures: a randomized clinical trial; Impact of smoking status on fracture-related infection characteristics and outcomes; Reassessing empirical antimicrobial choices in fracture-related infections; Development and validation of the Nottingham Trauma Frailty Index (NTFI) for older trauma patients

Gram-negative organisms are increasingly seen as causative pathogens in orthopaedic fracture surgery, which might necessitate a change in antibiotic prophylaxis protocols. A single-centre retrospective review of antibiogram results from all patients treated for fracture-related infection (FRI) was conducted. Subgroup analysis was undertaken to identify any host, injury or treatment variables predisposed to Gram-negative infection. The bacteriological results of 267 patients who underwent surgical treatment for FRI were analysed. Pathogens were isolated in 216 cases (81%), of which 118 (55%) were Gram-negative infections. Fractures involving the tibia and femur (p=0.007), the presence of soft tissue defect (p=0.003) and bone defects (p=0.001) were associated with an increased risk of developing a Gram- negative FRI. Gram-negative fracture-related infections were associated with injuries experiencing bone loss and those requiring soft tissue reconstruction. It is, therefore, prudent to consider extended Gram-negative directed antimicrobial prophylaxis in these cases to prevent the development of fracture-related infection

Aim. To conduct a systematic review and meta-analysis comparing the development of early and late fracture-related infections (FRI) following closed and open fractures in HIV-positive and HIV-negative patients. Method. A systematic literature search was conducted using MEDLINE through the OVID interface, ProQuest, Web of Science, The Cochrane Library and Scopus. Only studies involving HIV-positive who underwent operative fixation (internal or external) of open or closed fractures, with a HIV-negative control group, were considered eligible. Following eligibility assessment, studies were included with the main outcome of interest being the development of either early or late fracture-related infection at the site of surgery in patients with open and closed fractures. Results. Eleven studies were included (n = 2634). The studies’ follow-up periods were between one and 39 months with an average of 11 months. Three studies were conducted before the introduction of ARV (anti-retroviral) therapy (1994) and two did not involve any patients on ARV's. Across the entire group, for both open and closed fractures, the risk of a fracture-related infection was greater in HIV-positive patients (Odds ratio (OR) = 1.61; 95% CI = 0.93–2.79, p = 0.04). When looking at closed fractures treated operatively, an OR = 4.59 was found in HIV-positive patients in terms of the risk of fracture-related infection (95% CI = 0.30–68.99, p < 0.001). Open fractures showed similar results with an OR of 3.48 in HIV-positive patients (95% CI = 0.55 – 21.99, p < 0.001). Studies performed prior to the widespread introduction of anti-retroviral therapy and/or did not have any patients on antiretroviral therapy showed a greater infection risk in patients living with HIV infection with OR 3.53 (95% CI = 1.85 – 6.74, p = 0.36). However, studies performed in the era after the introduction of antiretroviral therapy showed no increase of infection risk for HIV-positive patients with an OR = 0.91 (95% CI = 0.58 – 1.43, p = 0.76). Conclusions. The assumption that HIV infection increases the risk for fracture-related infection remains unsubstantiated. The introduction of anti-retroviral therapy may have confounded the issue and we noted an apparent decrease in the risk in later studies. More data is required from well-designed larger studies to inform future analysis