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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., Competing Interests: Declaration of competing interest No conflict., (Copyright © 2024. Published by Elsevier Ltd.)

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest with respect to the preparation and writing of this article., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Open fractures are still a challenge in orthopaedic trauma surgery, and compared to closed fractures, the rate of complications including fracture-related infection (FRI) remains significantly higher. Although different guidelines on prevention of FRI have been published in past decades, the current recommendations vary significantly. The objectives of this international questionnaire were to evaluate clinical practice procedures for the prevention of FRI in open fractures and to evaluate adherence to available guidelines., Methods: A 17-item questionnaire regarding prophylaxis against infection in fracture care was administered by SurveyMonkey® and was sent via blast e-mail to all users of AOTrauma (Davos, Switzerland)., Results: Overall, 1197 orthopaedic trauma surgeons answered the survey. Although cephalosporins were the most commonly prescribed agents for perioperative antibiotic prophylaxis (PAP) in open fractures, a total of 13 different antibiotics were mentioned in the survey. Furthermore, the duration of PAP was extremely variable with a tendency towards longer treatment periods with increasing open fracture severity. The majority of surgeons (71%) agreed that the optimal duration of PAP was not well defined in the literature. The use of local anti-infective agents varied significantly, although all options received additional votes with increasing injury severity. Some of the other surgical aspects addressed in this review were associated with debridement and irrigation. A delay of six hours from injury to the first debridement was acceptable to 47% of surgeons, but delays were tolerable. Normal saline was the solution used most often for wound irrigation in open fractures (89%), with low-pressure irrigation being applied most commonly (55%)., Conclusions: This international survey provided an overview of clinical practice in FRI prevention, particularly in open fracture cases. The treatment of these serious injuries remains heterogeneous. A major issue is the lack of consensus concerning type and duration of PAP. Furthermore, there seems to be no agreement on the indication for the use of local anti-infective agents. Overall, it is unknown what the repercussions are of this lack of internationally accepted guidelines on daily clinical practice, but it is clear that standardised treatment protocols are preferable in the current medical landscape., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: One of the most challenging musculoskeletal complications in modern trauma surgery is infection after fracture fixation (IAFF). Although infections are clinically obvious in many cases, a clear definition of the term IAFF is crucial, not only for the evaluation of published research data but also for the establishment of uniform treatment concepts. The aim of this systematic review was to identify the definitions used in the scientific literature to describe infectious complications after internal fixation of fractures. The hypothesis of this study was that the majority of fracture-related literature do not define IAFF., Material and Methods: A comprehensive search was performed in Embase, Cochrane, Google Scholar, Medline (OvidSP), PubMed publisher and Web-of-Science for randomized controlled trials (RCTs) on fracture fixation. Data were collected on the definition of infectious complications after fracture fixation used in each study. Study selection was accomplished through two phases. During the first phase, titles and abstracts were reviewed for relevance, and the full texts of relevant articles were obtained. During the second phase, full-text articles were reviewed. All definitions were literally extracted and collected in a database. Then, a classification was designed to rate the quality of the description of IAFF., Results: A total of 100 RCT's were identified in the search. Of 100 studies, only two (2%) cited a validated definition to describe IAFF. In 28 (28%) RCTs, the authors used a self-designed definition. In the other 70 RCTs, (70%) there was no description of a definition in the Methods section, although all of the articles described infections as an outcome parameter in the Results section., Conclusion: This systematic review shows that IAFF is not defined in a large majority of the fracture-related literature. To our knowledge, this is the first study conducted with the objective to explore this important issue. The lack of a consensus definition remains a problem in current orthopedic trauma research and treatment and this void should be addressed in the near future., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

One of the most challenging complications in trauma surgery is infection after fracture fixation (IAFF). IAFF may result in permanent functional loss or even amputation of the affected limb in patients who may otherwise be expected to achieve complete, uneventful healing. Over the past decades, the problem of implant related bone infections has garnered increasing attention both in the clinical as well as preclinical arenas; however this has primarily been focused upon prosthetic joint infection (PJI), rather than on IAFF. Although IAFF shares many similarities with PJI, there are numerous critical differences in many facets including prevention, diagnosis and treatment. Admittedly, extrapolating data from PJI research to IAFF has been of value to the trauma surgeon, but we should also be aware of the unique challenges posed by IAFF that may not be accounted for in the PJI literature. This review summarizes the clinical approaches towards the diagnosis and treatment of IAFF with an emphasis on the unique aspects of fracture care that distinguish IAFF from PJI. Finally, recent developments in anti-infective technologies that may be particularly suitable or applicable for trauma patients in the future will be briefly discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Fracture-related infection (FRI) is a common and serious complication in trauma surgery. Accurately estimating the impact of this complication has been hampered by the lack of a clear definition. The absence of a working definition of FRI renders existing studies difficult to evaluate or compare. In order to address this issue, an expert group comprised of a number of scientific and medical organizations has been convened, with the support of the AO Foundation, in order to develop a consensus definition. The process that led to this proposed definition started with a systematic literature review, which revealed that the majority of randomized controlled trials in fracture care do not use a standardized definition of FRI. In response to this conclusion, an international survey on the need for and key components of a definition of FRI was distributed amongst all registered AOTrauma users. Approximately 90% of the more than 2000 surgeons who responded suggested that a definition of FRI is required. As a final step, a consensus meeting was held with an expert panel. The outcome of this process led to a consensus definition of FRI. Two levels of certainty around diagnostic features were defined. Criteria could be confirmatory (infection definitely present) or suggestive. Four confirmatory criteria were defined: Fistula, sinus or wound breakdown; Purulent drainage from the wound or presence of pus during surgery; Phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; Presence of microorganisms in deep tissue taken during an operative intervention, as confirmed by histopathological examination. Furthermore, a list of suggestive criteria was defined. These require further investigations in order to look for confirmatory criteria. In the current paper, an overview is provided of the proposed definition and a rationale for each component and decision. The intention of establishing this definition of FRI was to offer clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It is important to note that the proposed definition was not designed to guide treatment of FRI and should be validated by prospective data collection in the future., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Fracture-related infection (FRI) is one of the most challenging musculoskeletal complications in orthopaedic-trauma surgery. Although the orthopaedic community has developed and adopted a consensus definition of prosthetic joint infections (PJI), it still remains unclear how the trauma surgery community defines FRI in daily clinical practice or in performing clinical research studies. The central aim of this study was to survey the opinions of a global network of trauma surgeons on the definitions and criteria they routinely use, and their opinion on the need for a unified definition of FRI. The secondary aims were to survey their opinion on the utility of currently used definitions that may be at least partially applicable for FRI, and finally their opinion on the important clinical parameters that should be considered as diagnostic criteria for FRI., Methods: An 11-item questionnaire was developed to cover the above-mentioned aims. The questionnaire was administered by SurveyMonkey and was sent via blast email to all registered users of AO Trauma (Davos, Switzerland)., Results: Out of the 26'563 recipients who opened the email, 2'327 (8.8%) completed the questionnaire. Nearly 90% of respondents agreed that a consensus-derived definition for FRI is required and 66% of the surgeons also agreed that PJI and FRI are not equal with respect to diagnosis, treatment and outcome. Furthermore, "positive cultures from microbiology testing", "elevation of CRP", "purulent drainage" and "local clinical signs of infection" were voted the most important diagnostic parameters for FRI., Conclusion: This international survey infers the need for a consensus definition of FRI and provides insight into the clinical parameters seen by an international community of trauma surgeons as being critical for defining FRI., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Staphylococci are the most common pathogens causing orthopaedic device-related infections (ODRI). The treatment of these infections often involves multiple surgical procedures combined with systemic antibiotic therapy to treat the infection and restore functionality. Older patients frequently present with a compromised health-status and/or low bone quality, and despite growing importance their outcomes are not well described to date. The primary aim of the current study is to describe outcomes in older patients with ODRIs and to determine if they demonstrate lower cure rates and greater risk for complications in contrast to younger patients., Patients and Methods: Patients treated with an ODRI of the lower extremity at our institution were included in this study. Demographic data, comorbidities and infecting organisms were recorded. Older adult patients were defined as those aged 60 and older. At two-year follow-up post-discharge, we recorded the clinical course, the Lower-Extremity-Functional-Score, the patient reported general health status (SF-12-questionnaire) and the status of infection. The antibiotic resistance pattern of the disease causing pathogens was analysed and compared between the two age groups., Results: In total, 163 patients (age: 19-94 years) with a staphylococcal ODRI were included. Sixty-four of these infections occurred in older patients, which showed a significantly higher mortality rate (9%). Within follow-up period recurrence of infection occurred significantly more frequently in younger patients (41%) than in older patients (17%). At two-years follow-up cure, which was defined as eradication of infection and terminated therapy, was achieved in 78% of younger and 75% of older patients. However, an ODRI resulted in older patients in a significantly worse functional outcome and impaired physical quality of live, as well as more frequently in an on-going infection, such as a persisting fistula (14% versus 3% in younger patients). Disease causing staphylococci, isolated from older patients showed more frequently a methicillin or multi-drug resistance than those associated with infections in younger patients., Conclusions: ODRIs in older patients demonstrated higher morality rates rate, poor functional outcome and higher rates of persistent infections. A compromised health status and a poor bone quality may play a crucial role in this specific patient cohort., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Fracture fixation devices are implanted into a growing number of patients each year. This may be attributed to an increase in the popularity of operative fracture care and the development of ever more sophisticated implants, which may be used in even the most difficult clinical cases. Furthermore, as the general population ages, fragility fractures become more frequent. With the increase in number of surgical interventions, the absolute number of complications of these surgical treatments will inevitably rise. Implant-related infection and compromised fracture healing remain the most challenging and prevalent complications in operative fracture care. Any strategy that can help to reduce these complications will not only lead to a faster and more complete resumption of activities, but will also help to reduce the socio-economic impact. In this review we describe the influence of implant design and material choice on complication rates in trauma patients. Furthermore, we discuss the importance of local delivery systems, such as implant coatings and bone cement, and how these systems may have an impact on the prevalence, prevention and treatment outcome of these complications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Implant-related infection is a challenging complication in musculoskeletal trauma surgery. In the present study, we examined the role of implant material and surface topography as influencing factors on the development of infection in an experimental model of plating osteosynthesis in the rabbit., Methods: The implants included in this experimental study were composed of: standard Electropolished Stainless Steel (EPSS), standard titanium (Ti-S), roughened stainless steel (RSS) and surface polished titanium (Ti-P). Construct stability and load-to-failure of Ti-P implants was compared to that of Ti-S implants in a rabbit cadaveric model. In an in vivo study, a rabbit humeral fracture model was used. Each rabbit received one of three Staphylococcus aureus inocula, aimed at determining the infection rate at a low, medium and high dose of bacteria. Outcome measures were quantification of bacteria on the implant and in the surrounding tissues, and determination of the infectious dose 50 (ID50)., Results: No significant differences were observed between Ti-S and Ti-P regarding stiffness or failure load in the cadaver study. Of the 72 rabbits eventually included in the in vivo study, 50 developed an infection. The ID50 was found to be: EPSS 3.89×10(3) colony forming units (CFU); RSS 8.23×10(3) CFU; Ti-S 5.66×10(3) CFU; Ti-P 3.41×10(3) CFU. Significantly lower bacterial counts were found on the Ti-S implants samples compared with RSS implants (p<0.001) at the high inoculum. Similarly, lower bacterial counts were found in the bone samples of animals in the Ti-S group in comparison with both RSS and EPSS groups, again at the high inoculation dose (p<0.005)., Conclusion: No significant differences were seen in susceptibility to infection when comparing titanium and steel implants with conventional or modified topographies. Ti-P implants, which have previously been shown in preclinical studies to reduce complications associated with tissue adherence, do not affect infection rate in this preclinical fracture model. Therefore, Ti-P implants are not expected to affect the infection rate, or influence implant stability in the clinical situation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)