Fracture-related Infection Research Articles

Multidisciplinary approach and host optimization for fracture-related infection management

In orthopaedic trauma, fracture-related infections (FRI) are still dreadful challenges that can cause non-union, amputation and even death. Standardization of general treatment strategies for FRI is still lacking. Due to the complexity of FRI, a multidisciplinary approach addressing host status, state of the fracture and causative microorganism has been applied in the management of FRI. Surgical treatment, antibiotic therapy and host optimization for FRI were summarized and discussed. The goal of this review is to provide an overview and summary of current approaches of FRI management and to make suggestions on FRI prevention and treatment based on multidisciplinary principles.

The DAIR-procedure in fracture-related infection–When and how

This narrative review discusses treatment strategies and key considerations guiding decisions in the surgical management of fracture-related infections (FRI). Treatment options primarily revolve around two approaches: debridement antibiotics and implant retention (DAIR), or implant exchange, either in a one or multiple-stage strategy. Several considerations, including time since infection onset, implant type, stability, causative pathogens, host physiology, and soft tissue conditions, inform the choice of surgical intervention for FRI. Current literature supports the preference for a DAIR approach in cases with a short duration of ongoing symptoms, a stable implant with satisfactory fracture reduction, and a viable soft tissue envelope. Conversely, one- or multiple-stage implant exchange is deemed beneficial in instances of compromised local and systemic host physiology, mature biofilm, difficult-to-treat pathogens, intramedullary implants, and cases involving reinfections or failed DAIR procedures. Notably, these recommendations draw parallels from periprosthetic joint infection treatment strategies, constrained by the limited availability of randomized controlled trials comparing these options specifically in acute FRI. In conclusion, future perspectives call for extensive investigations into biofilm maturation and the impact of time on treatment outcomes. Additionally, there is a need for a standardized classification system for FRI to enhance the comparability of treatment outcomes in FRI management.

Recent advancements and future directions in fracture related infections: A scoping review

Fracture-related infections (FRIs) are complex challenges in orthopedic and trauma surgery, driving ongoing advancements in diagnostics, therapeutics, and management strategies. This scoping review examines recent progress and future directions in FRI management. Diagnostic enhancements encompass standardized definitions, improved biomarkers, advanced microbiological techniques, and innovative imaging modalities. Promising future diagnostics may include point-of-care testing, advanced imaging with enhanced specificity, and machine learning algorithms. Advancements in implant technology emphasize materials science, surface modifications, and personalized 3D printing, enhancing durability and antimicrobial efficacy. Immunomodulatory therapies targeting T cell dysfunction offer potential in addressing FRI chronicity. Enzybiotics and phages present promising alternatives to combat antibiotic resistance, with enzybiotics demonstrating effectiveness against biofilm-associated infections. Patient optimization, multidisciplinary approaches and specialized reference centers play vital roles in comprehensive FRI management, particularly crucial in resource-constrained settings. Collaboration and investment in research and technology are imperative for harnessing the full potential of these advancements and improving global FRI management outcomes. Addressing these complexities necessitates a multifaceted approach integrating clinical expertise, technological innovation, and global cooperation to optimize patient care and mitigate the burden of FRI worldwide.

New diagnostic techniques for diagnosing facture-related infections

The diagnosis of fracture-related infections (FRI) is challenging and requires interdisciplinary efforts. Many diagnostic approaches are based on the algorithms established for prosthetic joint infections (PJI). Data specific to FRI are limited. Microbiological diagnostics include tissue culture, sonication, and molecular methods. Novel metagenomic analyses are increasingly being used in clinical diagnostic practice. In addition to bacterial detection, the study of host tissue factors has the potential to transform the diagnostics of FRI by facilitating the assesment of clinical significance in clinical samples. The integration of host tissue analysis into microbiology reports has great potential to improve the diagnosis of FRI. This mini-review describes the potential improvement of diagnostic techniques by integrating new approaches into the diagnostic algorithm of fracture-related infections.

Management of Fracture-Related Infection in Conflict Zones: Lessons Learned from Medical Missions to Gaza

Background/Objectives: Fracture-related infections (FRIs) are a significant complication in conflict zones, where limited resources and damaged infrastructure complicate orthopedic care. Methods: This study retrospectively reviews the management of FRIs during medical missions to Gaza from April to July 2024. Results: Among 135 patients treated for war-related fractures, 30% were identified with suspected FRIs, which were primarily following explosive injuries. Contributing factors to the high incidence of infection included malnutrition, poor sanitation, and the scarcity of sterile surgical supplies. The absence of standard infection control measures further complicated treatment. Conclusions: These findings highlight the critical need for a comprehensive approach that incorporates infection prevention, sustainable healthcare planning, and quality assurance tailored to the realities of conflict zones. The study underscores the importance of international support to ensure the availability of essential medical supplies and to develop effective, context-specific strategies for infection management. By applying these insights, healthcare providers can improve patient outcomes and reduce the burden of FRIs in resource-limited settings affected by conflict.

Initial treatment of severe soft-tissue injuries in closed and open fractures to prevent fracture-related infection

The management of soft tissue damage during fracture treatment requires surgical proficiency and meticulous care adhering to established treatment protocols. This approach is paramount for minimizing the risk of potentially limb- or even life-threatening complications such as fracture-related infection (FRI) in all age groups. There is a general consensus on essential measures such as wound assessment, surgical debridement and early use of antibiotics. Treatment should always be based on the correct classification of the fracture and the corresponding soft tissue injury, but needs to be adapted to the individual patient considering general health status, secondary diagnoses and currently available treatment options.

Phage therapy: A primer for orthopaedic trauma surgeons

Phage therapy (PT) continues to attract interest in the fight against fracture-related infection (FRI), particularly for recurring infections that have not been resolved using conventional therapeutic approaches. The journey PT has taken from early clinical application in the pre-antibiotic era to its recent reintroduction to western clinical practice has been accelerated by the increased prevalence of multi-drug resistant (MDR) pathogens in the clinic. This review will present PT's potential as a precise, adaptable, and effective treatment modality, with a focus on patient and phage selection, as well as the various administration protocols currently applied to patients. The challenges for PT, for example the most optimal application technique and dosing, are also discussed and underscore the importance of personalized approaches and the urgent need for more robust clinical evidence. Future perspectives, including phage engineering and innovative delivery systems will be discussed, as they may broaden the applicability of PT to a point where it may become a standard rather than an option of last resort for orthopedic infection management.

Assessing diagnostic accuracy: 18F-FDG PET-CT scans in low-grade infection detection among post-traumatic long bone non-unions; a literature review and clinical data

IntroductionThe diagnosis of low-grade infection in post-traumatic long bone non-unions poses challenges due to the absence of clinical signs. This study aimed to review the available literature on the diagnostic accuracy of imaging techniques for low-grade infections and assess the diagnostic accuracy of 18F-FDG PET-CT scans for low-grade infection in post-traumatic long bone non-unions. MethodsA mini-review was conducted using Pubmed in March 2024. A retrospective study was conducted including adult patients with a long bone non-union, suspected of infection. All patients underwent 18F-FDG PET-CT scans as the index test before surgical intervention, with peri‑operative cultures obtained during surgery serving as the reference standard. Quantitative analyses were performed on the standardized uptake value (SUV) measurements obtained from the 18F-FDG PET-CT scans. Diagnostic accuracy measures including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminatory ability of SUV measurements. ResultsLiterature suggests that 18F-FDG PET-CT is the most accurate imaging technique to detect low-grade infections. The study included a total of 51 18F-FDG PET-CT scans and cultures from 50 patients with long bone non-unions. The diagnostic accuracy was found to be 0.67 (95 % CI 0.44–0.87). The PPV and NPV were calculated as 0.79 (95 % CI 0.53–1.00) and 0.52 (95 % CI 0.30–0.73), respectively. Quantitative analyses of SUV measurements demonstrated a low level of accuracy, with all area under the curve (AUC) values < 0.75 and ROC curves showing a trajectory fairly parallel to the diagonal line. Conclusion and discussionThe findings of this study indicate that in post-traumatic long bone non-unions, where a low-grade fracture-related infection (FRI) is suspected, the 18F-FDG PET-CT has a performance that is advantageous over other imaging techniques. A careful interpretation of the scan results is warranted, possibly including the quantitative analysis on tracer uptake as an adjunct. Nevertheless, the diagnostic accuracy in this condition is not as good as in early-onset FRI cases, and this should be taken into account when treating these challenging cases.

The role of tranexamic acid for infection prevention after fracture fixation

Despite the measures employed, fracture-related infections remain a concern after fracture fixation worldwide. Recently, the role of tranexamic acid as a protective drug against postsurgical infections in joint replacement and orthopedic trauma surgery has been proposed, where tranexamic acid has been associated with less surgical wounds complications and infectious complications including periprosthetic joint infection. The mechanism through which tranexamic acid exerts a protective effect against peri-implant infection is still the subject of debate. Although some authors hypothesize an indirect effect inhibiting the formation of postoperative hematoma, there are several studies that show a direct antibacterial effect of the drug against the capacity of bacterial aggregation, even avoiding biofilm formation, favoring the immune response of the host and the action of antibiotics. The purpose of this narrative review is to show the current role of tranexamic acid in orthopedic trauma, specifically its relationship with the prevention of infections related to implants.

Improving the microbiological diagnosis of fracture-related infection and prosthetic joint infection through culturing sonication fluid in Bactec blood culture bottles.

Sonication of surgically removed implants appears to optimize the microbiological diagnosis in orthopedic implant-associated infections (OIAI). However, reports of infection with negative cultures can still reach high rates. A study evaluating the inoculation of sonication fluid into blood culture bottles (SFBCB) in patients with fracture-related infection (FRI) and prosthetic joint infection (PJI) is necessary. This study compared the accuracy SFBCB over the conventional sonication fluid cultures (CSFC) and tissue culture (TC). Consecutive patients who underwent implant removal surgeries due to any reason had their implants sonicated according to standardized method. Definitions of PJI and FRI were based upon criteria by European Bone and Joint Infection Society (EBJIS) and Metsemakers, respectively. Between three to five intraoperative tissue samples were processed. The implant`s sonication fluid was seeded onto sheep blood agar, chocolate agar, thioglycolate broth and on tryptic soy broth for CSFC, while was also inoculated into blood culture bottles and incubated in the automated system during 5 days for SFBCB. Overall, 74 patients were analyzed, of which 57 with OIAI (48 FRI and 09 PJI) and 17 aseptic failures (03 arthroplasties and 14 osteosynthesis). Interestingly, SFBCB demonstrated significantly higher sensitivity compared to CSFC (96.5% [95% CI, 88-100] vs. 78.9% [95% CI, 66-89], p = 0.004), and to TC (96.5% [95% CI, 88-100], vs. 57.9% [95% CI, 44-71], p < 0.001), whereas there were no significant differences in specificity between the three methods. In comparison to CSFC and TC, SFBCB improved sensitivity for diagnosing OIAI without compromising specificity.

Key-risk factors for fracture-related infection after ankle surgery: a retrospective study

Background: Fracture-related infection (FRI) is a serious complication following ankle fracture surgery, with significant implications for patient outcomes. This study aimed to identify the key risk factors associated with FRI in a cohort of patients undergoing surgical fixation of ankle fractures. Methods: A retrospective analysis was conducted on 261 patients who underwent open reduction and internal fixation (ORIF) for ankle fractures between 2019 and 2021. Patient demographics, comorbidities, and surgical details were extracted from medical records. The primary outcome was the development of FRI within one year postoperatively. Logistic regression analysis was used to identify independent predictors of infection. Results: The mean age of the patients was 61.8 years (SD=16.5), with 69.3% being female. The overall infection rate was 8%. Significant predictors of FRI included smoking (OR=13.643, p=0.002), peripheral vascular disease (OR=17.684, p&lt;0.001), and diabetes mellitus (OR=11.309, p=0.002). Gender, congestive heart failure, obesity, and age were not statistically significant predictors of infection. Conclusion: This study identifies smoking, peripheral vascular disease, and diabetes mellitus as significant risk factors for FRI following ankle fracture surgery. These findings underscore the importance of targeted interventions to manage these comorbidities in high-risk patients to reduce the incidence of postoperative infections. Further research is needed to explore the role of other potential factors and to develop effective prevention strategies.

Non-tuberculous mycobacterial bone and joint infections - a case series from a tertiary referral centre in Australia.

Non-tuberculous mycobacteria (NTM) are rare causes of bone and joint infection (BJI) and there is limited evidence on which to base management decisions. This study describes 1 year of experience from a multi-disciplinary BJI team which collects data on all cases reviewed at a tertiary referral centre in Queensland, Australia. The database was interrogated for all cases in which NTM were recovered from operative samples. Individual chart review was performed to collect the details of each case. A total of seven cases were managed between 1st February 2021 and 28th February 2022, comprising one patient with chronic osteomyelitis, three with fracture-related infections, two with prosthetic joint infections, and one with infection of a synthetic ligament graft. In contrast to pulmonary NTM infections, most patients were clinically well and immunocompetent, and most infections were propagated by direct inoculation. Time to diagnosis was unknown in three patients, with 1, 2, 2, and 5 months for the remaining four. Rapid growing NTM were diagnosed on routine cultures and specific mycobacterial cultures were confirmatory. Management was characterized by multiple stage surgical procedures and prolonged antimicrobial regimens. Antimicrobial complications were common; however, all patients were infection free at their latest follow up. Despite the inherent limitations, these results suggest that routinely ordering mycobacterial culture is of low yield. There is potential for shorter-term oral antimicrobial treatments. Prospective research is required to optimize treatment regimens and durations.

Prehospital Antibiotic Administration for Suspected Open Fractures: Joint COT/OTA/ACEP/NAEMSP/NAEMT Position Statement

One of the primary concerns associated with open fractures is the development of a fracture-related infection (FRI). To minimize the risk of developing an FRI and subsequent morbidity, prophylactic antibiotics should be administered to patients with open fractures as soon as possible. While the antibiotic recommendations for severe open fractures are somewhat debatable, the use of a cephalosporin remains a mainstay of prophylactic treatment. Though administration of prehospital antibiotics does represent an expansion of EMS responsibilities, there have been several other treatment expansions in the prehospital setting, such as the administration of tranexamic acid and the application of pelvic binders. The administration of antibiotics, specifically cefazolin, is inexpensive, technically simple, and does not require special storage. The following recommendations are supported by and represent consensus of the COT, OTA, ACEP, NAEMSP and NAEMT with regards to prehospital antibiotic prophylaxis for suspected fractures: In a responsive patient with no history of penicillin or cephalosporin allergy, the administration by EMS of a 1st generation cephalosporin should be performed after the management of life threats. This intervention should not delay transport. In an obtunded patient, the administration by EMS of a 1st generation cephalosporin should be performed after the management of life-threats. This intervention should not delay transport. In a responsive patient with a documented penicillin allergy, the administration by EMS of a 1st generation cephalosporin should be performed with close monitoring after the management of life-threats. This intervention should not delay transport.

Development and Validation of a Preclinical Canine Model for Early Onset Fracture-Related Infections

Development and Validation of a Preclinical Canine Model for Early Onset Fracture-Related Infections

Salvage of a comminuted proximal tibial polymicrobial infected non-union with antibiotic loaded bio-composite and intramedullary nailing: a case report

Background. Management of open proximal metaphyseal fractures poses a significant challenge and is fraught with complications. These injuries are severe, often accompanied by extensive soft tissue and vascular damage, leading to high risks of infection and long-term disability. Case presentation. A 72-year-old male was severely injured in a road traffic accident. Plain X-rays and CT angiogram identified a comminuted proximal tibial fracture with transection of the popliteal artery and vein. Initial emergency treatment included fasciotomies, external fixation, and vascular primary repair. On the 12th day of admission, the patient underwent open reduction and internal fixation (ORIF) with dual plate fixation using a two incision technique. A plastic surgeon performed skin grafting, harvested from the patient’s thigh, to allow closure of his fasciotomy wounds immediately following ORIF. Four weeks post-operatively, the patient developed a wound breakdown over the lateral fasciotomy site, exposing the metal plates with a small defect developing on the medial fasciotomy wound in tandem. The patient’s course was further complicated by persistent polymicrobial infections. Over 6 months of antibiotic regimes, operative intervention was ultimately required. All of the infected metal implants were removed, the non-union sites were aggressively debrided. The tibial canal was reamed to prepare for a tibial nailing. An antibiotic loaded bio-composite was then inserted through the non-union sites into the canal followed by an intramedullary nail. A blocking screw was used to address the procurvatum deformity in the sagittal plane. The patient currently shows signs of recovery, mobilizing over short distances, weight-bearing with assistive aids and with healing wounds and early signs of callus formation on recent CT scans and plain X-rays. Conclusions. The management of complex tibial fractures with vascular involvement demands an aggressive multidisciplinary approach and continuous adaptability in treatment plans to address the evolving challenges of such severe injuries. This case exemplifies the utility of injectable antibiotic-loaded bio-composites in a limb-salvage setting and their ability to provide high doses of local antibiotics to an infection site which, in conjunction with appropriate stable fixation and systemic antibiotics, can aid in eradicating and treating fracture-related infections.

Antibiotic-Loaded Hydrogel for the Treatment of Lower-Limb Fracture-Related Infections: A Single Center's Multidisciplinary Experience.

A fracture-related infection (FRI) is a severe complication of an orthopedic trauma, often leading to challenging treatments and poor outcomes. The surgical strategies are typically categorized into one-stage or two-stage procedures, with the use of systemic and local antibiotics being crucial for infection management. This study assessed the efficacy of an antibiotic-loaded hydrogel (ALH) applied over the internal fixation devices for treating FRIs, comparing the outcomes between the one-stage (OS) and two-stage (TS) reconstructions. This retrospective study included 17 patients with an FRI treated using the ALH at a single center. The patients were divided into OS and TS reconstruction groups. The data on demographics, surgical procedures, antibiotic regimens, and outcomes were collected. The primary and secondary outcomes included the infection cure rate, bone union, complications, and reoperation rates. Among the 17 patients (mean age 48.5 years, 16 males), infections were predominantly in the tibia, with 12 chronic and 5 acute cases. Seven patients had monomicrobial infections, and nine had multidrug-resistant pathogens. No significant differences were found between the OS and TS groups in terms of the infection cure rate, bone union, or complications. One patient in the OS group experienced an infection recurrence, and bone healing was achieved in all but one case. Additional complications included delayed wound closure in two cases and implant failure in one case, requiring a reoperation. The ALH demonstrated potential as an effective local antibiotic treatment for FRIs, particularly in the one-stage reconstructions, allowing for a safe application of internal fixation devices. However, further research with larger sample sizes and longer follow-ups is needed to validate these findings.

Biofilm Formation, Antibiotic Resistance, and Infection (BARI): The Triangle of Death.

Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays a decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing to infection chronicity and increasing morbidity and mortality. Research exploring the association between biofilm maturation and antibiotic resistance in orthopaedics primarily addresses aspects related to quality of life and physical function; however, little exists on life-threatening conditions and mortality. Understanding the intrinsic relationship between biofilm maturation, bacterial resistance, and mortality is critical in all fields of medicine. In the herein narrative review, we summarize recent evidence regarding biofilm formation, antibiotic resistance, and infection chronicity (BARI), the three basic components of the "triangle of death" of FRI, and its implications. Preoperative, perioperative, and postoperative prevention strategies to avoid the "triangle of death" of FRI are presented and discussed. Additionally, the importance of the orthopaedic trauma surgeon in understanding new tools to combat infections related to orthopaedic devices is highlighted.

Risk factors for fracture-related infections after low-velocity gunshot fractures to the pelvis

BackgroundAlthough treatments have improved dramatically in recent years, mortality following gunshot wounds (GSW) to the pelvis continue to range between 3 and 20 %. This project was designed to determine the incidence and risk factors associated with pelvic fracture-related infection (FRI) following GSWs to the pelvis given the paucity of evidence regarding this complication. MethodsA retrospective review of 13 years (1/2010–12/2022) of patients with GSW to the pelvis was performed. Patients meeting inclusion criteria underwent chart review for the development of pelvic FRI and the following additional data elements were extracted: demographics, presence and type of bowel injury, operations performed, complications, use of postoperative antibiotics (≤24 h vs. >24 h), surgical osseous debridement, presence of retained bullet fragments, and bullet trajectory. Discrete variables were analyzed using Wilcoxon rank-sum test, chi-square, and Fischer's exact test. Pearson correlation coefficients were calculated for continuous variables. Results242 patients were included in the study. Concomitant bowel injury was present in 108 patients (45 %). Eleven patients (4.5 %) developed FRI, all of whom had a concomitant bowel injury (p < 0.001). Neither the presence of retained bullet fragments nor the bullet trajectory (through bowel before the bone) was associated with FRI. Antibiotic duration >24 h was not associated with a lower rate of pelvic FRI. ConclusionDevelopment of FRI after a GSW to the pelvis occurs in 4.5 % of patients and is significantly associated with concomitant bowel injury, specifically colonic injury. These findings can be used to help guide further studies on the role of prophylactic antibiotics or other strategies to prevent pelvic FRI.

Fracture-related infections after osteosynthesis for hip fracture are associated with higher mortality: A retrospective single-center cohort study.

Fracture-related infections (FRIs) after osteosynthesis for hip fractures have not been thoroughly investigated. Our primary aim was to assess the association between FRIs and mortality after osteosynthesis for hip fracture. Secondary aims were to investigate the incidence, microbiology, and general epidemiological aspects of these FRIs. This retrospective single-center study included 1,455 patients > 18 years old with non-pathological hip fractures treated with osteosynthesis between 2015 and 2019. Medical records were reviewed and FRIs were diagnosed based on current consensus criteria. The follow-up period was 2 years. Mortality was estimated using Kaplan-Meier survival analysis. Cox regression analyses were performed to investigate the potential association between FRIs, as a time-dependent variable, and increased mortality. The median age for the entire cohort was 83 (interquartile range 75-89) years and 69% were females. At the 2-year follow-up mark, the crude mortality rate was 33% in the non-FRI group and 69% (11 of 16 patients) in the FRI group. Cox regression analysis assessing mortality risk revealed a hazard ratio of 3.5 (95% confidence interval [CI] 1.9-6.4) when adjusted for confounders. The incidence of FRI was 1.1% (16 of 1,455 patients).Staphylococcus aureuswas the most common pathogen. Most FRI patients (94%) required at least 1 revision and 56% underwent ≥ 2 revision. We found an association between FRIs after hip fracture osteosynthesis and increased mortality, underscoring the critical need for FRI prevention measures in this frail patient group. The incidence and microbiological findings were consistent with previous studies.

The value of current diagnostic techniques in the diagnosis of fracture-related infections: Serum markers, histology, and cultures

Although fracture-related infection (FRI) is a serious complication following bone fractures, a comprehensive definition and diagnostic criteria have only emerged in recent years. According to this consensus definition, the diagnosis of FRI is based on preoperative and intraoperative suggestive or confirmatory criteria. Serum markers, histology, and microbiological cultures are considered to play a crucial role in the FRI diagnostic pathway. However, at the time of publication of the FRI consensus definition in 2018 and its update in 2020, limited data was available on the accuracy of these diagnostic methods. This review aims to provide an overview of recent publications and discuss whether new evidence has been obtained regarding the value of these current diagnostic techniques.Meanwhile, several studies have confirmed the limited prognostic value of C-reactive protein, erythrocyte sedimentation ratio, and white blood cell count. Other serologic markers for preoperative diagnosis of FRI with promising diagnostic performance are d-dimer, plasma fibrinogen, platelet count to mean platelet volume ratio, and a risk prediction model that includes soft tissue injury type and fracture complexity in addition to blood markers. However, their true diagnostic value in daily clinical practice needs to be investigated in further studies. Data on histology in FRI diagnosis is still limited, but its potential as a confirmatory criterion seems to lie in its high specificity. Recent studies indicate that tissue culture exhibits moderate sensitivity and high specificity, with sensitivity improvements achieved by sampling of five specimens and long-term culture. Implant sonication also appears to enhance the sensitivity of culture and the detection rate of polymicrobial infections.In conclusion, the true value of diagnostic techniques is difficult to assess, in part because it is measured against a gold standard that is itself imperfect and still evolving, but also because of methodological differences in sample processing or the use of different thresholds. Nevertheless, this review has identified that the value of current diagnostic techniques is high when used in combination. To draw more accurate conclusions about the value of serum markers, histology, and culture including sonication, future studies should be prospective and utilize a greater standardization in sampling and methodological protocols.