Treatment of fracture-related infection in Latin America (FRILA). Proposal for a multicentre regional registry.

Postoperative bone infection is a severe complication in the treatment of fractures. The management of this pathology is challenging, but recent advances have been made to achieve standardization that can help diagnosis and decision-making. However, we are unaware of studies validating these models in Latin America. Therefore, this study aims to collect data from patients with fracture-related infections treated in different institutions in Latin America to create a registry that will assist in future clinical decision-making regarding the diagnostic process and the surgical and medical treatment of these patients.

Vitamin D Receptor Genetic Variations May Associate with the Risk of Developing Late Fracture-Related Infection in the Chinese Han Population.

Variations in the vitamin D receptor (VDR) gene are related to several inflammatory disorders. However, the potential links between such alternations and the risk of developing late fracture-related infection (FRI) remain unclear. This study investigated associations between genetic variations in the VDR and susceptibility to late FRI in the Chinese Han population. Between January 2016 and December 2019, 336 patients with late FRI and 368 healthy controls were genotyped six VDR genetic variations, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820). Significant associations were observed between rs7975232 and FRI susceptibility in the recessive (P = 0.019, OR = 0.530, 95% CI 0.310-0.906) model. Patients with AA genotype had a relatively higher level of serological vitamin D (20.6 vs. 20.3 vs. 17.9 ng/ml) (P = 0.021) than those of AC and CC genotypes. Although no statistical differences were observed, potential correlations may exist between rs1544410 (dominant model: P = 0.079, OR = 0.634), rs2228570 (dominant model: P = 0.055, OR = 0.699), and rs4516035 (dominant model: P = 0.065, OR = 1.768) and the risk of FRI development. In the Chinese cohort, ApaI was associated with a decreased risk of developing FRI, and patients with the AA genotype had a higher vitamin D level. Further studies are required to assess the role of genetic variations in BsmI, FokI, and GATA in the pathogenesis of late FRI.

Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae.

A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient's wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient's K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.

Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study.

Although several studies have shown promising clinical outcomes of phage therapy in patients with orthopedic device-related infections, questions remain regarding the optimal application protocol, systemic effects, and the impact of the immune response. This study provides a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection (FRI) caused by Staphylococcus aureus. In a prevention setting, phage in saline (without any biomaterial-based carrier) was highly effective in the prevention of FRI, compared to systemic antibiotic prophylaxis alone. In the subsequent study involving treatment of established infection, daily administration of phage in saline through a subcutaneous access tube was compared to a single intraoperative application of a phage-loaded hydrogel and a control group receiving antibiotics only. In this setting, although a possible trend of bacterial load reduction on the implant was observed with the phage-loaded hydrogel, no superior effect of phage therapy was found compared to antibiotic treatment alone. The application of phage in saline through a subcutaneous access tube was, however, complicated by superinfection and the development of neutralizing antibodies. The latter was not found in the animals that received the phage-loaded hydrogel, which may indicate that encapsulation of phages into a carrier such as a hydrogel limits their exposure to the adaptive immune system. These studies show phage therapy can be useful in targeting orthopedic device-related infection, however, further research and improvements of these application methods are required for this complex clinical setting. IMPORTANCE Because of the growing spread of antimicrobial resistance, the use of alternative prevention and treatment strategies is gaining interest. Although the therapeutic potential of bacteriophages has been demonstrated in a number of case reports and series over the past decade, many unanswered questions remain regarding the optimal application protocol. Furthermore, a major concern during phage therapy is the induction of phage neutralizing antibodies. This study aimed at providing a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection caused by Staphylococcus aureus. Phage therapy was applied as prophylaxis in a first phase, and as treatment of an established infection in a second phase. The development of phage neutralizing antibodies was evaluated in the treatment study. This study demonstrates that phage therapy can be useful in targeting orthopedic device-related infection, especially as prophylaxis; however, further research and improvements of these application methods are required.

Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model.

Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. Staphylococcus aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be upregulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (P=0.22, Fisher's exact test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.

A murine Staphylococcus aureus fracture-related infection model characterised by fracture non-union, staphylococcal abscess communities and myeloid-derived suppressor cells.

A fracture-related infection (FRI) is a serious complication that can occur after surgical fixation of bone fractures. Affected patients may encounter delayed healing and functional limitations. Although it is well established that Staphylococcus aureus (S. aureus) is the main causative pathogen of an FRI, the pathophysiology of an S. aureus-induced FRI is not well characterised over time. Therefore, an experimental study in mice comparing S. aureus-inoculated and non-inoculated groups was performed that particularly focused on staphylococcal abscess communities (SACs) and host cellular response. C57Bl/6N female mice received a double osteotomy of the femur, which was stabilised using a titanium 6-hole MouseFix locking plate and four screws. Animals were either S. aureus-inoculated or non-inoculated and euthanised between 1 and 28 d post-surgery. Histopathological evaluation showed normal bone healing for non-inoculated mice, whereas inoculated mice had no fracture consolidation and severe osteolysis. Within the bone marrow of inoculated mice, SACs were observed from 7 d, which increased in size and number over time. A fibrin pseudocapsule enclosed the SACs, which were surrounded by many Ly6G+ neutrophils with some Ly6C+ monocytes and F4/80+ macrophages, the majority of which were viable. The abscesses were encapsulated by fibrin(ogen), collagen and myofibroblasts, with regulatory T cells and M2 macrophages at the periphery. Only bone marrow monocytes and neutrophils of inoculated mice displayed functional suppression of T cells, indicative of myeloid-derived suppressor cells. The present study revealed that an FRI in mice is persistent over time and associated with osteolysis, SAC formation and an immunosuppressive environment.

Bifidobacterium adolescentis supplementation attenuates fracture-induced systemic sequelae.

The gut microbiota is an important contributor to both health and disease. While previous studies have reported on the beneficial influences of the gut microbiota and probiotic supplementation on bone health, their role in recovery from skeletal injury and resultant systemic sequelae remains unexplored. This study aimed to determine the extent to which probiotics could modulate bone repair by dampening fracture-induced systemic inflammation. Our findings demonstrate that femur fracture induced an increase in gut permeability lasting up to 7 days after trauma before returning to basal levels. Strikingly, dietary supplementation with Bifidobacterium adolescentis augmented the tightening of the intestinal barrier, dampened the systemic inflammatory response to fracture, accelerated fracture callus cartilage remodeling, and elicited enhanced protection of the intact skeleton following fracture. Together, these data outline a mechanism whereby dietary supplementation with beneficial bacteria can be therapeutically targeted to prevent the systemic pathologies induced by femur fracture.

[Fracture-related infections in traumatology : Current standards and new developments in diagnostics and treatment]. / Implantatassoziierte Infektionen in der Traumatologie : Aktuelle Standards und neue Entwicklungen in der Diagnostik und Behandlung.

BACKGROUND: The high demands that fracture-related infections put on patients, physicians and the healthcare system have led to the establishment of a international group of experts called the Fracture-Related Infection (FRI) Consensus Group, whose aim is to develop evidence-based treatment recommendations. DIAGNOSIS: Fracture-related infections are classified according to the time of occurrence, extent and treatment options. The diagnostic algorithm distinguishes between confirmatory and suggestive diagnostic criteria. If there are indications of an infection, tissue biopsy with microbiological and histological workup is recommended to confirm the diagnosis. THERAPY: The primary objective of FRI treatment is to achieve fracture consolidation, while avoiding osteomyelitis. Therapeutic options are removal of the implant, eradication of the infection with implant retention or suppression of FRI. A multidisciplinary team is recommended to develop a patient-specific, optimized surgical and antimicrobial therapy.

Pathogen identification in 84 Patients with post-traumatic osteomyelitis after limb fractures.

BACKGROUND: Chronic osteomyelitis is a serious complication of orthopedic trauma. Residual bacteria after incomplete debridement and/or bacterial colonization, bacterial biofilm formation, and generation of antibiotic-resistant bacterial strains in the microtubule system of compact bones due to irrational use of antibiotics often make the condition more prolonged, recurrent, and refractory. The passive immunotherapy targeting the protein components of bacteria has become an area of intense research interest, for which identifying the bacterial isolates in different areas at different time points remains a key step. Few multicenter randomized controlled trials have investigated the epidemiological data of pathogens in different areas, and there is a lack of timely and dynamic data that can inform clinical treatment. METHODS: A total of 5,268 patients with limb fractures were treated in our center from January 1, 2012, to December 31, 2015, among whom 108 were diagnosed with post-traumatic osteomyelitis (PTO) based on clinical manifestations, imaging findings, and pathology. Bacteria cultures showed positive results in 84 patients. The clinical manifestations (including the infection site) were analyzed. The distribution and drug resistance of pathogens were analyzed and summarized based on the M-100-S22 protocol [Clinical and Laboratory Standards Institute® (CLSI) 2012, USA]. RESULTS: The incidence of PTO in limbs was 2.1% (n=108), and the bacterial cultures were positive in 84 patients (84/108, 77.8%). The infection sites included the tibia and fibula (n=40, 47.6%), femur (n=20, 23.8%), ulna and radium (n=11, 13.1%), humerus (n=5, 6%), patella (n=5, 6%), and calcaneus (n=3, 3.6%). In total, 104 of the following bacterial strains were identified: 56 strains of gram-positive bacteria (53.9%), among which Staphylococcus aureus (n=39, 37.5%) and Staphylococcus epidermis (n=6, 5.8%) were the most dominant bacteria, with both being sensitive to ampicillin, quinupristin, linazolamide, tigarycline, nitrofurantoin, and vancomycin; 48 strains of gram-negative bacteria (46.1%), among which Escherichia coli (n=16, 15.4%) and Enterobacter cloacae (n=11, 10.6%) were the most common bacteria, with both being sensitive to thiomycin; mixed infections were detected in 18 cases (21.4%). CONCLUSIONS: The incidence of PTO in the Zunyi area is similar to the national level. The most common site of infection is the lower extremity. Bacterial infections (mainly infection caused by a single bacterial type) were observed in 77.8% of the cases. Staphylococcus aureus is the most common pathogenic bacteria, followed by Escherichia coli and Enterobacter cloacae. The antibiotic-resistant bacteria have characteristic distributions in different regions.

Fracture-related infection: current methods for prevention and treatment.

Introduction: Fracture-related infection (FRI) is a serious complication related to orthopedic trauma, both from an infectious disease and a surgical point of view. The lack of scientific data with respect to diagnostic criteria and treatment principles of this entity has hampered efforts for an evidence-based approach and, as such, practices to prevent and treat FRI are often extrapolated from peri-prosthetic joint infection (PJI) literature. Recently, consensus guidelines were developed with respect to prevention, diagnosis and treatment of FRI.Areas covered: This review will define FRI and approaches to prevent and treat this complication will be discussed, with an emphasis on antimicrobial and surgical considerations. Guidelines focusing on FRI will be highlighted and aspects of pre-clinical research with imminent translational potential described.Expert opinion: New strategies are currently under investigation to improve the outcome of this sometimes-devastating complication. Local delivery of antimicrobials seems to be a promising approach; however, further high-quality clinical research is necessary to demonstrate efficacy. Delivery mechanisms for local antimicrobials include polymethyl methacrylate, implant coatings, collagen fleece, hydrogels and ceramics. The reintroduction of antimicrobials such as bacteriophage therapy has demonstrated promise in the management of drug-resistant organisms.

Focused high-energy extracorporeal shockwaves as supplemental treatment in a rabbit model of fracture-related infection.

Focused high-energy extracorporeal shockwave therapy (fhESWT) is used to improve fracture healing in cases of nonunion. In addition, it has been shown to have direct antibacterial effects. We evaluated fhESWT as an adjunct to conventional treatment in a clinically relevant rabbit model of fracture-related infection (FRI). A humeral osteotomy in 31 rabbits was fixed with a seven-hole locking compression plate. FRI was established with a clinical Staphylococcus aureus isolate. After 2 weeks, a revision surgery was performed with debridement, irrigation, and implant retention. Rabbits then received: no further treatment (controls); shockwaves (4000 impulses with 23 kV at days 2 and 6 after revision); systemic antibiotics (rifampin and nafcillin); or the combination of antibiotics and shockwaves. Treatments were applied over 1 week. Blood cultures were taken before and after shockwave sessions. After another 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 bacteremia. All the rabbits were infected at revision surgery as determined by the bacteriological culture of debrided materials. fhESWT in combination with antibiotic treatment lowered the bacterial burden 100-fold compared with antibiotic treatment alone in all samples (P = .38). This effect was most prevalent for the implant sample (P = .08). No significant effect was seen for fhESWT alone compared with untreated controls. No signs of bacteremia occurred in blood cultures and organs. fhESWT appears safe and could be a helpful adjunct to conventional treatment in certain difficult-to-treat FRIs.

[Clinical Features and Prognosis Factors of Spinal Tuberculosis in Northern Tunisia: A Case Series of 60 Patients]. / Profil clinique et facteurs pronostiques du mal de Pott au nord de la Tunisie : à propos de 60 cas.

Spondylodiscitis is a common but potentially serious form of extra-pulmonary tuberculosis. Very few descriptions are known from Tunisia. We have conducted a retrospective study including 60 cases of spinal tuberculosis, performed over a period of 20 years (1996-2016). The diagnosis was retained on bacteriological, radiological and anatomopathologic evidence. Sixty cases including 31 women and 29 men of spinal tuberculosis were involved. The mean age was 54.4 ±â€…21.3 years. The delay from onset to diagnosis was 6 months (1-14). Lumbar region was the most common infection site (68%). The magnetic resonance imaging has confirmed spinal infection in all cases. The percutaneous image guided spinal biopsy was conclusive in 24/42 cases (57.1%). All patients were put under anti-tuberculosis treatment with total treatment duration of 14 months. Fourteen patients underwent surgical act. The outcome was favorable in 42 cases (7%). Advanced age ≥ 65 years (P = 0.026), radiological evidence of spinal cord compression (P = 0.033) or abscess (P = 0.024), hyperleucocytosis higher than 11,500 elements/mm3 (0.031), or fractures on bone imaging (P = 0.018) and vertebral deformity (P < 0.001) were strongly linked to a bad outcome. Early diagnosis and treatment onset may ensure better outcomes and reduce neurological complications and vertebral deformity.

La spondylodiscite est une forme fréquente et potentiellement grave de tuberculose extrapulmonaire. Elle n'a été que peu décrite en Tunisie. Nous avons mené une étude rétrospective portant sur 60 cas de spondylodiscite tuberculeuse (SPDT) colligés sur une période de 20 ans (1996­2016) dans un centre hospitalier universitaire au nord de la Tunisie. Le diagnostic a été retenu sur des preuves bactériologiques, anatomopathologiques et radiologiques. Il s'agit de 31 femmes et de 29 hommes âgés en moyenne de 54,4 ±â€…21,3 ans. Le délai moyen de diagnostic était de six mois (1­14 mois). L'étage lombaire était le plus touché (68 %). L'imagerie par résonance magnétique était évocatrice du diagnostic dans tous les cas. La ponction-biopsie discovertébrale a permis de porter le diagnostic dans 24/42 cas (57,1 %), fondé sur des preuves histologiques. Tous les patients ont reçu un traitement antituberculeux d'une durée moyenne de 14 mois, associé à un geste interventionnel dans 14 cas. L'évolution était favorable dans 42 cas (70 %). Les facteurs de mauvais pronostic étaient l'âge avancé de plus de 65 ans (p = 0,026), la présence de signes radiologiques de compression médullaire (p = 0,033) ou d'abcès paravertébral (p = 0,024), l'hyperleucocytose initiale supérieure ou égale à 11 500 éléments/mm3 (p = 0,031), la présence de fracture vertébrale (p = 0,018) et d'une déformation vertébrale (p < 0,001). La SPDT est une maladie insidieuse dont le diagnostic et le traitement précoces sont la clé pour éviter les complications neurologiques et ostéoarticulaires.

Early outcome of culture-negative infection in open fractures of the lower limb: A prospective study.

Background: Culture-negative infections in open long bone fractures are frequently encountered in clinical practice. We aimed to identify the rate and outcome of culture-negative infections in open long bone fractures of lower limb. Methodology: A prospective cohort study was conducted from November 2015 to May 2017 on Gustilo and Anderson Grade III open long bone fractures of the lower limb. Demographic data, injury details, time from injury to receiving antibiotics and index surgical procedure were noted. Length of hospital stay, number of additional surgeries and occurrence of complications were also noted. Patients with infected open fractures were grouped as culture positive or culture negative depending on the isolation of infecting microorganisms in deep intraoperative specimen. The clinical outcome of these two groups was statistically analysed. Results: A total of 231 patients with 275 open fractures involving the femur, tibia or fibula were studied. There was clinical signs of infection in 84 patients (36.4%) with 99 fractures (36%). Forty-three patients (51.2%) had positive cultures and remaining 41 patients had negative cultures (48.8%). The rate of culture-negative infection in open type III long bone fractures in our study was 17.7%. There was no statistical difference in the clinical outcome between culture-negative and culture-positive infections. Conclusion: Failure to identify an infective microorganism in the presence of clinical signs of infection is routinely seen in open fractures and needs to be treated aggressively.

Prevalence of Deep Surgical Site Infection After Repair of Periarticular Knee Fractures: A Systematic Review and Meta-analysis.

Importance: Surgical management of periarticular knee fractures can be challenging, and adverse outcomes may be severe. Recent literature indicates that the rate of periarticular knee surgical site infection (SSI) may range from 2% to 88% depending on the fracture site. Objective: To examine the prevalence of deep SSI and the rate of septic arthritis after surgical repair of fractures around the knee. Data Sources: The electronic databases MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to July 1, 2018. Study Selection: Eligible studies had to specifically report deep SSI rates and include fractures in the distal femur, patella, tibial plateau, or proximal tibia. Risk factors that were associated with increased the risk of deep SSI were also examined. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were extracted by multiple investigators. Comprehensive Meta-Analysis software was used for the pooling of data, using either random-effects or fixed-effects models, with respect to the degree of statistical heterogeneity present. Data analyses were conducted in October 2019. Main Outcomes and Measures: The primary outcome was overall prevalence of deep SSI after periarticular knee fracture repair. The secondary outcomes were the overall prevalence of septic arthritis, risk factors associated with deep SSI, and the most commonly cultured bacteria specimens found periarticular knee infections. Results: Of 6928 articles screened, 117 articles met inclusion criteria and were included in analysis. Among 11 432 patients included in analysis, 653 patients (5.7%) experienced deep SSIs, most commonly among patients with proximal tibia fractures (56 of 872 patients [6.4%]). Among studies that included information on septic arthritis, 38 of 1567 patients (2.4%) experienced septic arthritis. The 2 most commonly reported bacteria were methicillin-resistant Staphylococcus aureus, found in 67 SSIs, and methicillin-susceptible S aureus, found in 53 SSIs. Sixty-two studies (53.0%) in the sample received a Coleman Methodological Score of poor (<50 points). Conclusions and Relevance: Deep SSIs occurred in nearly 6% of periarticular knee fracture repairs, and 2.4% of SSIs were associated with septic arthritis. Surgeons managing these injuries should be vigilant when wounds are not pristine. Efforts should be made to elevate the quality of research conducted not only in this subject but also in orthopedic surgery as a whole.

Clinical pathologies of bone fracture modelled in zebrafish.

Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The csf1ra mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with Staphylococcus aureus, neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput.This article has an associated First Person interview with the first author of the paper.

Implants induce a new niche for microbiomes.

Although much work is being done to develop new treatments, research and knowledge regarding factors underlying implant-related microbial colonization leading to infection are less comprehensive. Presence of microorganisms in and around implants clinically characterized as uninfected remains unknown. The objective of this study was to detect and identify bacteria and fungi on implants from various groups of patients with no prior indications of implant related infections. Patient samples (implants and tissue) were collected from five different hospitals in the Capital region of Denmark. By in-depth microbiological detection methods, we examined the prevalence of bacteria and fungi on 106 clinically uninfected implants from four patient groups (aseptic loosening, healed fractures, craniofacial complications and recently deceased). Of 106 clinically uninfected implants and 39 negative controls investigated, 66% were colonized by bacteria and 40% were colonized by fungi (p < 0.0001 compared to negative controls). A large number of microbes were found to colonize the implants, however, the most prevalent microbes present were not common aetiological agents of implant infections. The findings indicate that implants provide a distinct niche for microbial colonization. These data have broad implications for medical implant recipients, as well as for supporting the idea that the presence of foreign objects in the body alters the human microbiome by providing new colonization niches.

The value of quantitative histology in the diagnosis of fracture-related infection.

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.

Diagnostic challenges and future perspectives in fracture-related infection.

Fracture-related infection (FRI) is one of the most challenging complications in orthopaedic trauma surgery. It has severe consequences for patients and an important socio-economic impact. FRI has distinct properties and needs to be addressed interdisciplinary. Since criteria for the diagnosis of FRI are not standardized, an expert panel recently proposed a definition for FRI. In this review the current diagnostic modalities and an interdisciplinary diagnostic algorithm based on this recently published definition, are presented and future diagnostic techniques discussed. Since to date, there is no single universal diagnostic test available that gives the clinician the definitive diagnosis of FRI, it is mandatory to follow a standardized diagnostic algorithm to correctly diagnose FRI.

Local control of polymicrobial infections via a dual antibiotic delivery system.

BACKGROUND: Contaminated traumatic open orthopedic wounds are frequently complicated by polymicrobial contamination and infection. In high-risk wounds, the standard of care comprises debridement and irrigation combined with antibiotics which can be applied directly or combined with systemic antibiotics. Recently, bioabsorbable chitosan sponges have been shown to be an effective single-agent delivery device for local antibiotics with and without negative pressure wound therapy (NPWT). Severely contaminated orthopedic wounds, however, are often complicated by polymicrobial infections, necessitating multiple antibiotic agents. As such, the purpose of this study was to determine if a chitosan sponge would provide a suitable delivery vehicle for multiple antibiotics for the treatment of a polymicrobial infection in a large animal polytraumatic extremity wound model. METHODS: A complex polytraumatic extremity wound was created in 11 adult male Boer goats. Each wound was contaminated with a bioluminescent strain of S. aureus (1 ml of 108 colony forming units/ml) and of P. aeruginosa (1 ml of 108 CFU/ml) which are genetically engineered to allow quantification with a photon-counting camera. Six hours following initial wound creation and contamination, wounds were debrided and irrigated with low-pressure normal saline. The animals were randomized into one of two treatments: wet-to-dry dressings alone or a commercially available chitosan sponge loaded with 1 g vancomycin and 1.2 g of tobramycin. Each animal was then recovered and reimaged 48 h later for total bacteria content; tissue samples were taken from the wound bed to determine relative bacterial colonization. RESULTS: All animals in the chitosan sponge group saw significant reductions in overall bacterial load of S. aureus and P. aeruginosa (p = 0.001). The bioluminescence was also significantly reduced compared to the wet-to-dry dressing group (p = 0.0001). Furthermore, whereas the antibiotic sponge group displayed near complete eradication of bacteria, the wounds treated with the wet-to-dry dressings alone displayed a significant 2-log increase in total bacteria at 48 h p = 0.0001). S. aureus was the predominant species found in the wounds, comprising 95 and 99% of all bacteria found in the chitosan sponge and wet-to-dry, respectively. CONCLUSION: Dual antimicrobial therapy loaded in a chitosan sponge is an effective way to reduce polymicrobial infections traumatic extremity wound.

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.