Mario Morgenstern

Infection after fracture fixation: Current surgical and microbiological concepts.

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.

Antibiotic Resistance of Commensal Staphylococcus aureus and Coagulase-Negative Staphylococci in an International Cohort of Surgeons: A Prospective Point-Prevalence Study

Nasal colonization with antibiotic resistant bacteria represents both a risk factor for the colonized individual and their immediate contacts. Despite the fact that healthcare workers such as orthopedic surgeons are at a critical interface between the healthcare environment and an at-risk patient population, the prevalence of antibiotic resistant bacteria within the surgical profession remains unclear. This study offers a snapshot of the rate of nasal colonization of orthopedic surgeons with multi-resistant staphylococci including methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS). We performed a prospective, observational study obtained at a single time point in late 2013. The participants were active orthopedic, spine and head & neck surgeons from 75 countries. The prevalence of nasal carriage of the different bacteria and the corresponding 95% confidence interval were calculated. From a cohort of 1,166 surgeons, we found an average S. aureus nasal colonization rate of 28.0% (CI 25.4;30.6) and MRSA rate of 2.0% (CI 1.3;2.9), although significant regional variations were observed. The highest rates of MRSA colonization were found in Asia (6.1%), Africa (5.1%) and Central America (4.8%). There was no MRSA carriage detected within our population of 79 surgeons working in North America, and a low (0.6%) MRSA rate in 657 surgeons working in Europe. High rates of MRCoNS nasal carriage were also observed (21.4% overall), with a similar geographic distribution. Recent use of systemic antibiotics was associated with higher rates of carriage of resistant staphylococci. In conclusion, orthopedic surgeons are colonized by S. aureus and MRSA at broadly equivalent rates to the general population. Crucially, geographic differences were observed, which may be partially accounted for by varying antimicrobial stewardship practices between the regions. The elevated rates of resistance within the coagulase-negative staphylococci are of concern, due to the increasing awareness of their importance in hospital acquired and device-associated infection.

Orthopaedic device-related infection: current and future interventions for improved prevention and treatment

Orthopaedic and trauma device-related infection (ODRI) remains one of the major complications in modern trauma and orthopaedic surgery. Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, leading to infections that negatively impact clinical outcome and significantly increase healthcare expenditure. The following review summarises the microbiological profile of modern ODRI, the impact antibiotic resistance has on treatment outcomes, and some of the principles and weaknesses of the current systemic and local antibiotic delivery strategies. The emerging novel strategies aimed at preventing or treating ODRI will be reviewed. Particular attention will be paid to the potential for clinical impact in the coming decades, when such interventions are likely to be critically important. The review focuses on this problem from an interdisciplinary perspective, including basic science innovations and best practice in infectious disease. Cite this article: Moriarty TF, Kuehl R, Coenye T, et al. Orthopaedic device related infection: current and future interventions for improved prevention and treatment. EFORT Open Rev 2016;1:89-99. DOI: 10.1302/2058-5241.1.000037.

Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection

Staphylococcus epidermidis is a permanent member of the normal human microbiota, commonly found on skin and mucous membranes. By adhering to tissue surface moieties of the host via specific adhesins, S. epidermidis is capable of establishing a lifelong commensal relationship with humans that begins early in life. In its role as a commensal organism, S. epidermidis is thought to provide benefits to human host, including out-competing more virulent pathogens. However, largely due to its capacity to form biofilm on implanted foreign bodies, S. epidermidis has emerged as an important opportunistic pathogen in patients receiving medical devices. S. epidermidis causes approximately 20% of all orthopedic device-related infections (ODRIs), increasing up to 50% in late-developing infections. Despite this prevalence, it remains underrepresented in the scientific literature, in particular lagging behind the study of the S. aureus. This review aims to provide an overview of the interactions of S. epidermidis with the human host, both as a commensal and as a pathogen. The mechanisms retained by S. epidermidis that enable colonization of human skin as well as invasive infection, will be described, with a particular focus upon biofilm formation. The host immune responses to these infections are also described, including how S. epidermidis seems to trigger low levels of pro-inflammatory cytokines and high levels of interleukin-10, which may contribute to the sub-acute and persistent nature often associated with these infections. The adaptive immune response to S. epidermidis remains poorly described, and represents an area which may provide significant new discoveries in the coming years.

Fracture-related infection: A consensus on definition from an international expert group

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.

Staphylococcal orthopaedic device-related infections in older patients

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.

Definition of infection after fracture fixation: A systematic review of randomized controlled trials to evaluate current practice.

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 RCTs 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.

The missing effect of human recombinant Bone Morphogenetic Proteins BMP-2 and BMP-7 in surgical treatment of aseptic forearm nonunion

INTRODUCTION In this cohort study, the surgical revision concept of open compression plating and autologous bone grafting with and without additional application of BMP for treatment of aseptic ulna and/or radius shaft nonunion was evaluated. The purpose was to evaluate the clinical and radiological outcome, and to determine any difference in osseous healing, range of time between revision surgery and bone healing, and postoperative complications between the cohort groups. PATIENTS AND METHODS Between 01/2005 and 03/2015, a prospective, randomised, controlled cohort study was performed in a Level I Trauma Centre. Forty-nine patients were treated with the diagnosis of aseptic diaphyseal ulnar and/or radial shaft nonunion using compression plating and autologous bone grafting. Additional biological augmentation using BMP-2 or BMP-7 was performed in 24 patients. Clinical and radiological follow-up was performed six weeks, three and six months after revision surgery in accordance to the system by Anderson. RESULTS The study group consisted of 38 men and 11 women with a median age of 44 years (range 19-77). Twenty-four out of 49 patients obtained compression plating either with autologous iliac crest bone grafting (11/24 patients) or cancellous bone grafting (13/24 patients) and additional application of BMP-2 (4/24 patients) or BMP-7 (20/24 patients). The remaining 25 patients did not receive any additional application of BMP, but autologous bone grafting. The median follow-up was 15 months (range 6-54 months). Forty-six out of 49 nonunion healed within 12 months after revision surgery with a median time to union of six months. The clinical outcome, as assessed using the system by Anderson, as well as osseous healing, duration of time interval between revision surgery and bone healing, and postoperative complications did not demonstrate significant differences between the cohort groups. DISCUSSION Atrophic/oligotrophic forearm nonunion healed irrespective of additional application of BMP combined with autologous bone grafting. For successful treatment, radical resection of fibrous nonunion tissue and internal compression plate fixation is required with the aim of achieving high degree of rigid stability. Also, correction of angular deformities, restoration of length, and precise axial alignment of the distal radio-ulnar joint are mandatory prerequisites to successfully achieve bone healing.

Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome

ABSTRACT Staphylococcus epidermidis has emerged as an important opportunistic pathogen causing orthopedic-device-related infections (ODRI). This study investigated the association of genome variation and phenotypic features of the infecting S. epidermidis isolate with the clinical outcome for the infected patient. S. epidermidis isolates were collected from 104 patients with ODRI. Their clinical outcomes were evaluated, after an average of 26 months, as either “cured” or “not cured.” The isolates were tested for antibiotic susceptibility and biofilm formation. Whole-genome sequencing was performed on all isolates, and genomic variation was related to features associated with “cured” and “not cured.” Strong biofilm formation and aminoglycoside resistance were associated with a “not-cured” outcome (P = 0.031 and P < 0.001, respectively). Based on gene-by-gene analysis, some accessory genes were more prevalent in isolates from the “not-cured” group. These included the biofilm-associated bhp gene, the antiseptic resistance qacA gene, the cassette chromosome recombinase-encoding genes ccrA and ccrB, and the IS256-like transposase gene. This study identifies biofilm formation and antibiotic resistance as associated with poor outcome in S. epidermidis ODRI. Whole-genome sequencing identified specific genes associated with a “not-cured” outcome that should be validated in future studies. (The study has been registered at ClinicalTrials.gov with identifier NCT02640937.)

The unstable thoracic cage injury: The concomitant sternal fracture indicates a severe thoracic spine fracture

INTRODUCTION The thoracic cage is an anatomical entity composed of the upper thoracic spine, the ribs and the sternum. The aims of this study were primarily to analyse the combined injury pattern of thoracic cage injuries and secondarily to evaluate associated injuries, trauma mechanism, and clinical outcome. We hypothesized that the sternal fracture is frequently associated with an unstable fracture of the thoracic spine and that it may be an indicator for unstable thoracic cage injuries. PATIENTS AND METHODS Inclusion criteria for the study were (a) sternal fracture and concomitant thoracic spine fracture, (b) ISS≥16, (c) age under 50 years, (d) presence of a whole body computed-tomography performed at admission of the patient to the hospital. Inclusion criteria for the control group were as follows: (a) thoracic spine fracture without concomitant sternal fracture, (b)-(d) same as study cohort. RESULTS In a 10-year-period, 64 patients treated with a thoracic cage injury met inclusion criteria. 122 patients were included into the control cohort. In patients with a concomitant sternal fracture, a highly unstable fracture (AO/OTA type B or C) of the thoracic spine was detected in 62.5% and therefore, it was significantly more frequent compared to the control group (36.1%). If in patients with a thoracic cage injury sternal fracture and T1-T12 fracture were located in the same segment, a rotationally unstable type C fracture was observed more frequently. The displacement of the sternal fracture did not influence the severity of the concomitant T1-T12 fracture. CONCLUSIONS The concomitant sternal fracture is an indicator for an unstable burst fracture, type B or C fracture of the thoracic spine, which requires surgical stabilization. If sternal and thoracic spine fractures are located in the same segment, a highly rotationally unstable type C fracture has to be expected.