Willem-Jan Metsemakers

A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus.

Implant-associated bone infections caused by antibiotic-resistant pathogens pose significant clinical challenges to treating physicians. Prophylactic strategies that act against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are urgently required. In the present study, we investigated the efficacy of a biodegradable Polymer-Lipid Encapsulation MatriX (PLEX) loaded with the antibiotic doxycycline as a local prophylactic strategy against implant-associated osteomyelitis. Activity was tested against both a doxycycline-susceptible (doxy(S)) methicillin-susceptible S. aureus (MSSA) as well as a doxycycline-resistant (doxy(R)) methicillin-resistant S. aureus (MRSA). In vitro elution studies revealed that 25% of the doxycycline was released from the PLEX-coated implants within the first day, followed by a 3% release per day up to day 28. The released doxycycline was highly effective against doxy(S) MSSA for at least 14days in vitro. A bolus injection of doxycycline mimicking a one day release from the PLEX-coating reduced, but did not eliminate, mouse subcutaneous implant-associated infection (doxy(S) MSSA). In a rabbit intramedullary nail-related infection model, all rabbits receiving a PLEX-doxycycline-coated nail were culture negative in the doxy(S) MSSA-group and the surrounding bone displayed a normal physiological appearance in both histological sections and radiographs. In the doxy(R) MRSA inoculated rabbits, a statistically significant reduction in the number of culture-positive samples was observed for the PLEX-doxycycline-coated group when compared to the animals that had received an uncoated nail, although the reduction in bacterial burden did not reach statistical significance. In conclusion, the PLEX-doxycycline coating on titanium alloy implants provided complete protection against implant-associated MSSA osteomyelitis, and resulted in a significant reduction in the number of culture positive samples when challenged with a doxycycline-resistant MRSA.

The use of gentamicin-coated nails in complex open tibia fracture and revision cases: A retrospective analysis of a single centre case series and review of the literature.

INTRODUCTION Despite modern advances in fracture care, deep (implant-related) infection remains a problem in the treatment of tibia fractures. There is some evidence that antibiotic-coated implants are beneficial in the prevention of this sometimes devastating complication. In the following study we describe our results using a gentamicin-coated intramedullary tibia nail (Expert Tibia Nail (ETN) PROtect™) for the surgical treatment of complex open tibia fracture and revision cases. MATERIALS AND METHODS We describe the outcome of patients treated between January 2012 and September 2013, using a gentamicin-coated intramedullary tibia nail. Treatment indications included acute, Gustilo grade II-III, open tibia fractures or closed tibia fractures with long-term external fixation prior to intramedullary nailing and complex tibia fracture revision cases with a mean of three prior surgical interventions. Outcome parameters in this study were deep infection and nonunion. RESULTS In total, 16 consecutive patients with 16 tibia fractures were treated with a gentamicin-coated intramedullary nail. The overall patient population was subdivided into two groups. The first group consisted of 11 patients (68.8%) with acute fractures who were treated with a gentamicin-coated intramedullary nail. The second group consisted of 5 complex revision cases (31.2%). In our patient population no deep infections could be noted after the treatment with a gentamicin-coated tibia nail. Nonunion was diagnosed in 4 patients (25.0%), 1 of these was a revision case. CONCLUSIONS Musculoskeletal complications place a cost burden on total healthcare expenditure. Better understanding of the epidemiology and pathogenesis is essential because this can lead to prevention rather than treatment strategies. The purpose of the study was to evaluate a gentamicin-coated tibia nail in the prevention of deep (implant-related) infection. In our patient population no deep infections occurred after placement of the gentamicin-coated nail. Following this study and literature data, antibiotic-coated implants seem a potential option for prevention of deep infection in trauma patients. In the future this statement needs to be confirmed by large randomised clinical trials.

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.

Infection after fracture fixation of the tibia: Analysis of healthcare utilization and related costs

INTRODUCTION One of the most challenging complications in musculoskeletal trauma surgery is the development of infection after fracture fixation (IAFF). It can delay healing, lead to permanent functional loss, or even amputation of the affected limb. The main goal of this study was to investigate the total healthcare costs and length-of-stay (LOS) related to the surgical treatment of tibia fractures and furthermore identify the subset of clinical variables driving these costs within the Belgian healthcare system. The hypothesis was that deep infection would be the most important driver for total healthcare costs. PATIENTS AND METHODS Overall, 358 patients treated operatively for AO/OTA type 41, 42, and 43 tibia fractures between January 1, 2009 and January 1, 2014 were included in this study. A total of 26 clinical and process variables were defined. Calculated costs were limited to hospital care covered by the Belgian healthcare financing system. The five main cost categories studied were: honoraria, materials, hospitalization, day care admission, and pharmaceuticals. RESULTS Multivariate analysis showed that deep infection was the most significant characteristic driving total healthcare costs and LOS related to the surgical treatment of tibia fractures. Furthermore, this complication resulted in the highest overall increase in total healthcare costs and LOS. Treatment costs were approximately 6.5-times higher compared to uninfected patients. CONCLUSION This study shows the enormous hospital-related healthcare costs associated with IAFF of the tibia. Treatment costs for patients with deep infection are higher than previously mentioned in the literature. Therefore, future research should focus more on prevention rather than treatment strategies, not only to reduce patient morbidity but also to reduce the socio-economic impact.

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.

Prevention of fracture-related infection: a multidisciplinary care package

Fracture-related infection (FRI) remains a challenging complication. It may result in permanent functional loss or even amputation in otherwise healthy patients. For these reasons, it is important to focus attention on prevention. In treatment algorithms for FRI, antibiotic stewardship programmes have already proved their use by means of a multidisciplinary collaboration between microbiologists, surgeons, pharmacists, infectious disease physicians and nursing staff. A similar approach, however, has not been described for infection prevention. As a first step towards achieving a multidisciplinary care package for infection prevention, this review summarises the most recent guidelines published by the World Health Organization (WHO) and US National Institutes of Health Centers for Disease Control and Prevention (CDC), primarily focusing on the musculoskeletal trauma patient. The implementation of these guidelines, together with close collaboration between infection control physicians, surgeons, anaesthesiologists and nursing staff, can potentially have a beneficial effect on the rate of FRI after musculoskeletal trauma surgery. It must be stated that most evidence presented here in support of these guidelines was not obtained from musculoskeletal trauma research. Although most preventive measures described in these studies can be generalised to the musculoskeletal trauma patient, there are still important differences with nontrauma patients that require further attention. Future research should therefore focus more on this very defined patient population and more specifically on FRI prevention.

Are the current guidelines for surgical delay in hip fractures too rigid? A single center assessment of mortality and economics

PURPOSE Controversy remains around acceptable surgical delay of acute hip fractures with current guidelines ranging from 24 to 48 h. Increasing healthcare costs force us to consider the economic burden as well. We aimed to evaluate the adjusted effect of surgical delay for hip fracture surgery on early mortality, healthcare costs and readmission rate. We hypothesized that shorter delays resulted in lower early mortality and costs. METHODS In this retrospective cohort study 2573 consecutive patients aged ≥50 years were included, who underwent surgery for acute hip fractures between 2009 and 2017. Main endpoints were thirty- and ninety-day mortality, total cost, and readmission rate. Multivariable regression included sex, age and ASA score as covariates. RESULTS Thirty-day mortality was 5% (n = 133), ninety-day mortality 12% (n = 304). Average total cost was €11960, dominated by hospitalization (59%) and honoraria (23%). Per 24 h delay, the adjusted odds ratio was 1.07 (95% CI 0.98-1.18) for thirty-day mortality, 1.12 (95% CI 1.04-1.19) for ninety-day mortality, and 0.99 (95% CI = 0.88-1.12) for readmission. Per 24 h delay, costs increased with 7% (95% CI 6-8%). For mortality, delay was a weaker predictor than sex, age, and ASA score. For costs, delay was the strongest predictor. We did not find clear cut-points for surgical delay after which mortality or costs increased abruptly. CONCLUSIONS Despite only modest associations with mortality, we observed a steady increase in healthcare costs when delaying surgery. Hence, a more pragmatic approach with surgery as soon as medically and organizationally possible seems justifiable over rigorous implementation of the current guidelines.

Is open acute Achilles tendon rupture repair still justified? A single center experience and critical appraisal of the literature

INTRODUCTION Acute Achilles tendon ruptures are injuries with multiple treatment strategies with possibly far reaching consequences. Open repair is associated with a high complication rate, whereas percutaneous techniques are associated with higher re-rupture rates. The goal of this study was to evaluate the clinical outcome and economic burden of open surgical repair and define a medically and economically sound treatment protocol for acute Achilles tendon ruptures. METHODS Between June 2012 and December 2016 one hundred and five patients with an acute Achilles tendon rupture, treated in an open surgical manner, were studied retrospectively. All demographic, clinical and hospital-related costs were retrieved from the electronic patient database. ATRS questionnaires were sent to assess the functional outcome. A response rate of 70.5% was achieved. RESULTS We recorded a complication rate of 40%, respectively sural nerve hypoesthesia (14.3%), delayed wound healing (28.6%), infection (20.9%) and re-rupture (4.8%). Surgical resident, as primary operating surgeon was associated with a higher complication rate (p = 0.042). Overall, a median functional ATRS score of 17 (IQR 6.5-39.5) was recorded. Infection was associated with significantly higher total healthcare costs per patient as compared to re-rupture (€17,435 vs. €4,537, p = 0.013). The total cost for surgical debridement (n = 6) was approximately 5-times higher than for re-rupture (n = 5), €108,382 vs. €22,272. The median ATRS score for surgical debridement after infection and re-rupture did not differ significantly from the overall ATRS score, respectively 32 (IQR 21-63) and 28 (IQR 15-28). Nevertheless, a difference of 10 points is considered clinically relevant. CONCLUSION The overall functional outcome of open repair of Achilles tendon ruptures is rather good, however associated with a high complication rate, mainly due to wound problems and infection. Although several risk factors were identified, only the operating surgeon is modifiable. Considering the high total costs for surgical debridement in the context of infection compared to re-rupture surgery, despite equal functional outcome,we decided to change clinical practice to reduce the complication rate and healthcare costs. The outcome and precise costs for percutaneous repair will be addressed.

Insights into treatment and outcome of fracture-related infection: a systematic literature review

IntroductionStandardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients.MethodsA comprehensive search was performed in all scientific literature since 1990. Studies in English that described surgical patient series for treatment of FRI were included. Data were collected on diagnostic criteria for FRI, classifications used, surgical treatments, follow-up protocols, and overall outcome. A systematic review was performed according to the PRISMA statement. Proportions and weighted means were calculated.ResultsThe search yielded 2051 studies. Ninety-three studies were suitable for inclusion, describing 3701 patients (3711 fractures) with complex FRI. The population consisted predominantly of male patients (77%), with the tibia being the most commonly affected bone (64%), and a mean of three previous operations per patient. Forty-three (46%) studies described FRI at one specific location. Only one study (1%) used a standardized definition for infection. A total of nine different classifications were used to guide treatment protocols, of which Cierny and Mader was used most often (36%). Eighteen (19%) studies used a one-stage, 50 (54%) a two-stage, and seven (8%) a three-stage surgical treatment protocol. Ten studies (11%) used mixed protocols. Antibiotic protocols varied widely between studies. A multidisciplinary approach was mentioned in only 12 (13%) studies.ConclusionsThis extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago. Internationally accepted guidelines are urgently required to improve the quality of care for patients suffering from this significant complication.

Economics of open tibial fractures: the pivotal role of length-of-stay and infection

In order to define strategies to curb the continuing increase in healthcare costs, we describe the cost breakdown of open tibial fractures. Twenty-seven clinical and process variables were recorded retrospectively, and five main hospital related cost categories were defined. Three multivariate linear models were fitted to the data. Total healthcare costs of open tibial fractures were almost twice as high compared to closed fractures and mainly existed of hospitalization costs. Length-of-stay (LOS) was found to be the most important variable driving the healthcare costs of open tibial fractures. Deep infection lead to a 6-fold increase of LOS and 5-fold increase in total healthcare costs of open tibial fractures. Therefore, appropriate international consensus guidelines are required to improve not only the patient outcome (infection prevention) but also reduce overall healthcare cost by focusing on reducing the LOS.