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To reduce diabetes-related complications and to avoid futile procedures, foot and ankle surgeons need to understand the relative timings of catastrophic events, their incidence, and probabilities of transitions between disease states in diabetes in different patient populations. For this study, we tracked medical events (including an initial diagnosis of diabetes, ulcer, wound care, osteomyelitis, amputation, and reamputation, in order of severity) and the time between each such event in patients with diabetes, stratifying by sex, race, and ethnicity. We found that the longest average duration between the different lower extremity states was a diagnosis of diabetes to the occurrence of ulcer at 1137 days (38 months). The average durations of amputation to reamputation, osteomyelitis, wound care, and ulcer were 18, 49, 23, and 18 days, respectively. The length of each disease transition for females was greater, while those of the Hispanic population were shorter than in the total cohort. This knowledge may permit surgeons to time and tailor treatments to their patients, and help patients to address, delay, or avoid complications., (Copyright © 2024 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Because of the established path of bacterial entry and contamination-associated mechanisms, grade 3 open orthopedic fractures represent a substantial infection risk. The Eastern Association for the Surgery of Trauma (EAST) guidelines recommended covering Staphylococcus aureus and adding aminoglycoside gram-negative coverage. Local institutional guidelines rely on ceftriaxone for gram negative coverage and add methicillin-resistant Staphylococcus aureus coverage with vancomycin. Patients and Methods: The electronic health records of adults admitted for a grade 3 open fracture between January 1, 2016, and October 31, 2021, were retrospectively reviewed. Patients who received cefazolin and gentamicin (CZ+GM) or ceftriaxone and vancomycin (CRO+VA) as prophylaxis were included. We recorded the rate of a composite treatment failure outcome of receipt of antibiotic agents, infection-related hospitalization, or subsequent debridement for injury-site skin and soft tissue infection or osteomyelitis. The presence of acute kidney injury (AKI) was also evaluated. Results: There were 65 patients included in the CZ+GM group and 53 patients in the CRO+VA group. Patients in the CZ+GM group were younger (mean 42.6 compared with 50.6 years; p = 0.02). Otherwise, there were no significant differences between groups' demographics, mechanism and site of injury, timeline of care, or surgical interventions. More patients in the CZ+GM arm met the composite treatment failure outcome, but it was not statistically significant (45% vs. 32%; p = 0.2). There were similar rates of treatment failure at 30 days (21% vs. 26%; p = 0.5) and for only osteomyelitis (8% vs. 9%; p = 1). Conclusions: The trend in numerically lower treatment failure rates in the CRO+VA group across outcomes provides sufficient evidence to continue the current local recommendations. Given our sample size, type 2 error may have occurred, and studies with greater power should analyze this question.

Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulfate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an antibacterial effect locally. In vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET interaction, we investigated the effect of serum exposure on HA-TET binding in an antibacterial assay. Although, serum exposure reduced the zone of inhibition (ZOI) of Staphylococcus aureus, a significant ZOI could still be observed after pre-incubation of HA with serum. We could in addition show that zoledronic acid (ZA) competes for the same binding sites as TET and that exposure to high doses of ZA led to reduced TET-HA binding. In an in-vivo setting, we then confirmed that systemically administered TET seeks HA particles that were pre-implanted in muscle and subcutaneous pouches in rats and mice respectively, preventing HA particles from being colonized by S. aureus. Clinical Significance: This study describes a new drug delivery method that could prevent bacterial colonization of a HA biomaterial and reduce recurrences in bone infection., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria., (© 2022. The Author(s).)

Antibiotic-loaded chitosan pastes have shown advantages in the treatment and coverage of complex musculoskeletal defects. We added mannitol, previously shown to increase antibiotic susceptibility of biofilm, to an injectable chitosan/polyethylene glycol paste for delivery of antibiotics. Ground sponges (0.85% acetic acid solution, 1% chitosan, 0% or 2% mannitol, 1% polyethylene glycol) were hydrated using phosphate-buffered saline with 10 mg/ml amikacin and 10 mg/ml vancomycin added to form pastes. We inoculated rabbit radial defects with 10 5 colony-forming units of Staphylococcus aureus (UAMS-1) and inserted titanium pins into the cortical bone. Groups compared included mannitol blend pastes, non-mannitol blends, antibiotic-loaded bone cement, vancomycin powder, and no treatment controls. We harvested tissue samples and retrieved the pins retrieved at 3 weeks. All antibiotic-loaded groups lowered bacterial growth and colony-forming unit counts in soft and bone tissue and on titanium pins in in vivo studies. The results indicate this biomaterial is capable of eluting active antibiotics at concentrations that reduce bacterial growth on biomaterials and tissue, which, in turn, may prevent biofilm formation. Blends of chitosan and mannitol may be useful in prevention and treatment of osteomyelitis and implant-associated infections., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Background:  Osteoradionecrosis (ORN) is one of the most severe complications of free fibula reconstruction after radiotherapy. The gold standard treatment of osteomyelitis involves extensive debridement, antibiotics, and sufficiently vascularized muscle flap coverage for better circulation. Therefore, we hypothesized that free fibula flap with muscle could decrease the risk of ORN., Methods:  This study consisted of 85 patients who underwent reconstruction with free fibula flap in head and neck cancer by a single reconstructive surgeon at Kaohsiung Veterans General Hospital over a period of 19 years (1998-2016). Patients with postoperative adjuvant radiotherapy were included in the study and were grouped by either free fibula osteocutaneous flap or free fibula osteomyocutaneous flap (with flexor hallucis longus muscle), and the incidence of ORN was compared., Results:  Of the 85 patients, 15 were reconstructed with osteocutaneous fibula flap and 70 were with osteomyocutaneous fibula flap. The rate of ORN or osteomyelitis was significantly lower in the muscle group (18.6%, n  = 13/70 vs. 46.7%, n  = 7/15, p  = 0.020, Chi-square test)., Conclusion:  Vascularized muscle transfer increases perfusion of surrounding tissues and the bone flap, thereby decreasing the incidence of osteomyelitis or osteonecrosis., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: While the majority of pediatric osteomyelitis cases are acute in nature, a significant subset present with prolonged symptoms often associated with substantial morbidity. Little data exist to guide clinicians in the management of these infections. We sought to describe the epidemiology, clinical features and management of chronic osteomyelitis (CO) in children., Methods: We reviewed hospital admissions for CO from 2011 to 2018 at Texas Children's Hospital. Cases were included if symptoms lasted ≥28 days on presentation. Cases were classified as those associated with: (1) a contiguous focus of infection; (2) penetrating trauma; (3) orthopedic hardware; (4) postacute CO (PACO, those occurring after ≥28 days of therapy for acute osteomyelitis); and (5) primary hematogenous CO., Results: One hundred fourteen cases met inclusion criteria. The median patient age was 11.8 years and 35.9% had comorbidities. 70.2% of patients underwent ≥1 surgical procedure. A microbiologic etiology was identified in 72.8% of cases and Staphylococcus aureus was most common (39.4%). Contiguous focus of infection was more often associated with polymicrobial disease with or without Pseudomonas. Postacute CO was caused by S. aureus in 95%. The median duration of total therapy was 210 days. 26.3% of patients experienced treatment failure of which 46% underwent repeat hospital admission/surgery. There was no association between duration of intravenous therapy for CO and treatment failure., Conclusions: Children with CO represent a diverse group both in terms of pathogenesis and microbiology. Pathogenesis and clinical presentation can provide clues to microbiologic etiology. Prolonged intravenous therapy does not appear to improve outcomes in CO., Competing Interests: J.C.M. receives grant funding from the Agency for Healthcare Research and Quality (AHRQ R01HS026896) and is the local PI on a multicenter clinical trial sponsored by Nabriva Therapeutics unrelated to osteomyelitis; J.G.V. is a coinvestigator in this study. J.C.M. and J.G.V. are subinvestigators on studies sponsored by Merck and Allergan. J.C.M. has also received a donation of laboratory materials from Allergan for work unrelated to this manuscript. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The cell membrane-coated nanoparticles (MNPs) showed great potential in treating infectious disease due to their superior biofunctions in improving biocompatibility of nanoparticles and neutralization of pathogen or toxins. However, bone infection is accompanied with severe inflammation and bone loss, which also requires anti-inflammatory and osteoconductive treatment. The conventional membrane coating method has to undergo ultrasonication and extrusion procedures, which reduces the functionality of cell membrane and limits the choice of nanoparticles. In this study, we proposed an electroporation-based membrane coating strategy to facilitate the synthesis of MNPs to tackle those problems. Methods: Magnetic composite nanoparticles with osteoconductive Ca 3 (PO 4 ) 2 and bactericidal TiO 2 were assembled into macrophages through phagocytosis and then collected to expose in electric field for obtaining macrophage membrane-coating nanoparticles. By using molecular dynamics simulation and materials characterizations, the cell membrane coating efficiency was confirmed. The in vitro anti-bacterial and anti-inflammatory abilities were tested by bacteria culturing and immune cells activation. Then drug-resistant bacteria induced bone infection model was established to verify its in vivo therapeutic effects. Results: The coated membrane prepared through electroporation reserved the integrality of membrane structure and right-sidedness, with more functional proteins. Those led to the superior properties of recognition and adsorption with bacteria, toxins and inflammatory cytokines. Owing to the benefits of electroporation, the MNPs exhibited significant better antibacterial and anti-inflammatory abilities for enhancing the tissue repair process. Conclusion: This study provides a novel self-assembly cell membrane coating strategy by electroporation to construct multifunctional membrane-coating nanoparticles for bone infection treatment. This strategy not only improves the functions of coated membrane, but is also proved to be universal for varies nanoparticles or cells, indicating a great potential for future applications in the bioengineering field., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This report demonstrates that high levels of lameness can be induced by a limited bacterial challenge in drinking water for birds raised on litter flooring, comparable with lameness induced by the gold standard for inducing lameness, growth on suspended wire flooring. The bacterium used in the challenge was cultured from lesions in birds induced for bacterial chondronecrosis with osteomyelitis (BCO) in the wire-flooring model so the epidemiology appears similar. The litter-flooring model could better approximate broiler operations. Furthermore, the work demonstrates that 2 commercial probiotics (GalliProTect and GalliProMax) can reduce lameness in the bacterial challenge litter-flooring model. Lameness attributable to BCO is one of the most significant animal welfare issues for broiler production. The wire-flooring and litter-flooring models afford alternatives for understanding the etiology, and epidemiology of BCO, and development of management strategies to reduce lameness. Probiotics afford a promising management strategy. The results suggest that the probiotic protection may extend beyond just intestinal health and intestinal barrier function., (Copyright © 2020. Published by Elsevier Inc.)

The incidence of a fracture-related infection (FRI) can reach 30% of open tibia fractures (OTF). The use of antibiotic-coated implants is one of the newest strategies to reduce the risk of infection in orthopedic surgery. The aim of this study was to investigate the efficacy and safety of a gentamicin-coated tibia nail in primary fracture fixation (FF) and revision surgery (RS) of nonunion cases in terms of FRI incidence. We conducted a systematic review according to the PRISMA checklist on Pub-Med, Cochrane, and EMBASE. Of the 32 studies, 8 were included, for a total of 203 patients treated: 114 were FF cases (63% open fractures) and 89 were RS cases, of which 43% were infected nonunion. In the FF group, four FRI were found (3.8%): three OTF (Gustilo-Anderson III) and one closed fracture; bone healing was achieved in 94% of these cases. There were four relapses of infection and one new onset in the RS group; bone healing occurred in 88% of these cases. No side effects were found. There were no significant differences in terms of FRI, nonunion, and healing between the two groups. Gentamicin-coated tibia nail is an effective therapeutic option in the prophylaxis of high-risk fracture infections and in complex nonunion cases.

The feed additive Availa-ZMC was investigated for the ability to reduce lameness in broilers using 2 alternative models for inducing lameness. The mixture of organic trace minerals was effective in reducing lameness by 20% in the wire flooring model and 25% in the litter flooring model with the bacterial challenge. Lameness in both models is overwhelmingly attributable to bacterial chondronecrosis with osteomyelitis. The reduction in lameness was associated, at least in part, with enhanced intestinal barrier integrity mediated by elevated expression of tight junction proteins and stimulation of bactericidal killing of adherent peripheral blood monocytes obtained from the birds treated with Availa-ZMC. Lameness is a major animal welfare concern in broiler production. The wire flooring model and litter flooring model with the bacterial challenge are effective models for evaluation of management strategies for mitigating infectious causes of lameness., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: In this study, a novel oxygenated nanocomposite thin film, TaON-Ag, was investigated in vitro and in vivo to evaluate its biocompatibility and antibacterial ability., Material and Methods: The antibacterial ability of TaON-Ag nanocomposite-coated titanium (Ti) was evaluated using the Kirby-Bauer disk diffusion susceptibility test. The effects of TaON-Ag nanocomposite-coated metal on osteogenesis were further evaluated in an in vitro osteogenic culture model with rat marrow-derived mesenchymal stem cells (rMSCs). Furthermore, titanium rods coated with TaON-Ag were implanted into a rat femur fracture model either with or without osteomyelitis to investigate the effects of TaON-Ag in osteogenesis., Results: The TaON-Ag-coated Ti exhibited an effective antibacterial effect against Staphylococcus aureus , coagulase-negative Staphylococcus , and the Gram-negative strains Escherichia coli and Pseudomonas aeruginosa . Using an osteogenic culture with rMSCs and a rat femoral fracture model, the TaON-Ag-coated Ti did not interfere with the ossification of rMSCs in vitro or during fracture healing in vivo. Field-emission scanning electron microscopy (FE-SEM) revealed that coating with TaON-Ag could inhibit pathogen adhesion and biofilm formation in both Staphylococcus aureus and Escherichia coli., Conclusion: Using the proposed novel oxygenation process, TaON-Ag nanocomposite-coated Ti yielded robust biocompatibility and antibacterial ability against common microorganisms in orthopedic infections, thereby demonstrating potential for use in clinical applications., Competing Interests: Dr Chih-Chien Hu reports grants from Chang Gung Medical foundation, grants from Ministry of Science and Technology, Taiwan, during the conduct of the study. Professor Jang-Hsing Hsieh reports grants from Ministry of Science and Technology ROC, during the conduct of the study. The authors declare no other potential conflicts of interest for this work., (© 2020 Hu et al.)

Background: While increases in overdoses, viral hepatitis, and endocarditis associated with drug use have been well-documented in North Carolina, the full scope of invasive drug-related infections (IDRIs) has not. We characterized trends in IDRIs among hospitalized patients in North Carolina., Methods: We compared invasive infections that were related or not related to drug use among hospitalized patients aged 18-55 years based on retrospective review of administrative records from 2010-2018. Hospitalizations for endocarditis, central nervous system/spine infections, osteomyelitis, and septic arthritis were labeled as IDRIs if discharge codes included opioid and/or amphetamine misuse. Trends, rates, and distributions were calculated., Results: Among 44 851 hospitalizations for the specified infections, 2830 (6.3%) were IDRIs. The proportion of infections attributable to drug use increased from 1.5% (2010) to 13.1% (2018), and the rate grew from 1.2 to 15.1 per 100 000. Compared with those who had non-drug-related infections, patients with IDRIs were younger (median age, 35 vs 46 years), more likely to be non-Hispanic white (81% vs 56%), and had longer hospitalizations (median, 8 vs 6 days). 43% of hospitalizations for IDRIs involved infective endocarditis., Conclusions: The rate of IDRIs in North Carolina increased substantially during 2010-2018, indicating an urgent need for enhanced infection prevention, harm reduction, and addiction services aimed at community and inpatient settings., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment.

Background: Open fractures are among the most severe injuries observed in orthopedic patients. Treating open fractures is difficult because such patients with infections may require multiple operations and amputations. Furthermore, only a few studies have focused on antibiotic prophylaxis in open fractures and evaluated how to cover lost soft tissue to increase the success rate of reconstruction. We evaluated the risk factors for deep infection in lower limb Gustilo-Anderson (G-A) type III fractures., Materials and Methods: This retrospective study investigated patients who underwent surgical procedures for lower limb G-A type III fractures between January 2007 and January 2017 at our institution. We enrolled 110 patients with 114 lower limb G-A type III fractures (77 G-A type IIIA fractures and 37 G-A type IIIB fractures) who were followed up for at least 2 years. We compared patients presenting infections with those without infections by assessing the following factors: severe contamination, diabetes, smoking, Injury Severity Scale, segmental fracture, location of fracture, G-A classification, damage control surgery, methods of surgery, timing of fixation, combination of antibiotics used, duration of antibiotic prophylaxis, timing of wound closure, and soft-tissue reconstruction failure., Results: Eighteen fractures presented deep infections. Compared with patients without infections, patients developing infections differed significantly in terms of severe contamination (P < 0.01), G-A classification (P < 0.01), duration of antibiotic prophylaxis (P < 0.01), timing of wound closure (P < 0.01), and incidence of soft-tissue reconstruction failure (P < 0.01). Skin grafting was associated with significantly higher failure rates than muscle and free flap reconstructions (P = 0.04). Treatment with antibiotics was significantly longer in patients with drug-resistant bacterial infections than in those without infections (P < 0.01)., Conclusion: Early flaps rather than skin grafting should be used to cover G-A type IIIB fractures, because skin grafting resulted in the highest failure rate among soft-tissue reconstructions in open fractures. Longer duration of antibiotic use had a significant impact not only on deep infection rates but also on the presence of drug-resistant bacteria. These findings suggest that prolonged use of antibiotics should be avoided in cases of open fractures., Level of Evidence: Level IV retrospective observational study.

Bacterial osteomyelitis is a major clinical challenge in human and veterinary patients. This infection is an infrequent but feared complication of orthopedic surgery and is mainly caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of dalbavancin (dosed for either 7 or 14 days) in an MRSA-osteomyelitis tibial bone model. A total of 39 rats were included in the study. All animals received an inoculum of a clinical strain of MRSA (10 6 colony-forming units [CFU]) injected into the proximal tibia under general anesthesia. Dalbavancin was injected intraperitoneally for 7 or 14 days in 13 animals each; the remaining 13 animals received saline solution. After treatment, the animals were sacrificed. Infected tibiae were recovered for histological evaluation and microbiological analysis (MRSA count per gram of bone). Rats that received dalbavancin showed a statistically significant reduction of MRSA counts compared with the control group: median 0 CFU/g bone (14 days of dalbavancin) vs. 70 CFU/g bone (7 days of dalbavancin) and 1600 CFU/g bone (control). Histological evaluation showed typical signs of osteomyelitis in the control group, whereas there were no signs of bone infection in 92% of the rats that received 14 days of dalbavancin. According to this model, dalbavancin seems to have good efficacy for treating serious Gram-positive bone infections, including those caused by MRSA., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objectives: To determine the incidence, types, risk factors, identify organisms, and assess outcomes of surgical wound infections (SWIs) after cardiac surgery at a tertiary hospital in Riyadh, Saudi Arabia. Methods: This historical cohort study reviewed the chart of  patients who underwent cardiac surgery at King Khalid University Hospital, Riyadh, Saudi Arabia between January 2009 and December 2014. The proforma contained personal data, comorbidities, type of surgery, microbiological analysis, and management outcomes. Results: A total of 1241 patients were enrolled in the study comprising 1,032 (83.2%) men and 209 (16.8%) women. Forty (3.2%) patients developed SWI, of which 32 (2.5%) were superficial and 8 (0.7%) were deep. Gender, obesity, diabetes mellitus, non-use of statins, and coronary artery bypass graft (CABG) surgery were not significant predictors of infection in the study. Methicillin-susceptible Staphylococcus aureus was isolated predominantly in 45%, followed by Klebsiella and Pseudomonas species. Methicillin-resistant Staphylococcus aureus, Enterococcus faecium, and extended β-lactamase-producing gram-negative organisms were pathogens isolated in last 3 years of the review.  Simple and vacuum assisted closure therapies led to complete resolution in 32 (80%) patients, while 8 (20%) developed sternal osteomyelitis. All patients survived except one with a deep SWI who died of uncontrolled sepsis.  Conclusion: Despite the low incidence of postoperative SWIs, the risk of sternal osteomyelitis development persists. Meticulous choice of CABG components and appropriate postoperative management, especially detecting early signs of SWI could contribute to lower its incidence and complications.

The treatment of Gustilo type IIIB and IIIC open fractures remains a challenging problem, because the infection rate is 15-45%. Infection can lead to serious complications such as osteomyelitis or amputation. The intra-wound continuous negative pressure and irrigation treatment (IW-CONPIT) was developed for infected wounds and intractable ulcers, and is very effective in suppressing infection and accelerating wound healing. Here the IW-CONPIT was applied to severe open fractures for the purpose of preventing infection. After thorough debridement and lavage of the wound, bony stabilization is performed by external fixation. Dermal matrix is grafted onto any areas where the bone or tendon is exposed. A sponge containing two tubes is placed over the entire surface of the wound including the dermal matrix. Then it is covered with a film dressing to make the wound completely airtight. A bottle of physiologic saline solution is attached to one tube, and a continuous aspirator is attached to the other. This system maintains negative pressure on the wound surface, which is continuously irrigated. Thirty-five patients were treated with this method. A superficial infection developed in two cases but was resolved by additional debridement and continued application of IW-CONPIT. Complete wound healing was obtained with split thickness skin graft in all cases. There were no complications such as osteomyelitis, delayed bone union or amputation. IW-CONPIT was able to definitively prevent wound infection in Gustilo type ⅢB open fractures. We believe this method will become a standard treatment option for this condition.

Infection is a main cause of implant failure. Early implant-related infections often occur in the first 4 weeks post-operation. Inhibiting bacterial adhesion and biofilm formation at the early stage and promoting subsequent implant osseointegration are important for implant success. Our previous studies demonstrated that dimethylaminododecyl methacrylate (DMADDM) provided dental materials with antibacterial effects. In the present study, DMADDM and hydroxyapatite (HA) are loaded on to the titanium (Ti) surface via poly dopamine (PDA) self-polymerization. This local DMADDM-delivery Ti is referred as Ti-PHD. Here we report the two-staged capability of Ti-PHD: (1) in the first stage, releasing DMADDM during the high-infection-risk initial period post-implantation for 4 weeks; (2) then in the second stage, enhancing osteogenesis and promoting osseointegration. Ti-PHD has a porous surface with higher average roughness and greater hydrophilicity than pure Ti. Its biocompatibility is verified in vitro and in vivo. During the first 4 weeks of release, both DMADDM remaining on Ti surface and DMADDM released into the soaking medium greatly reduced the adherence and growth of pathogens. This is further confirmed by the prevention of bone destruction in a rat osteomyelitis model. After releasing DMADDM for 4 weeks, Ti-PHD promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and new bone formation around the implants in vivo. This article represents the first report on the two-staged, time-dependent antibacterial and osteogenesis effects of Ti-PHD, demonstrating its potential for clinical applications to inhibit implant-associated infections. STATEMENT OF SIGNIFICANCE: The present study develops a two-staged time-dependent system for local dimethylaminododecyl methacrylate (DMADDM) delivery via Ti implant (referred to as Ti-PHD). DMADDM and hydroxyapatite (HA) are loaded on to the Ti surface with poly dopamine (PDA). Ti-PHD can release DMADDM during the high-risk period of infection in the first stage, and then promote osseointegration and new bone formation in the second stage. This bioactive and therapeutic Ti is promising to inhibit infections and enhance implant success., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Treatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes., Methods: In this study, a novel open fracture mouse model was developed using Staphylococcus aureus ( S. aureus ) and single-stage intramedullary fixation. The model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus . In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period., Results: We found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray., Conclusion: Vancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. This novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans., Competing Interests: The authors have that there are no conflicts of interest., (Copyright © 2019 A. I. Stavrakis et al.)

Reconstruction of a bone defect using the Masquelet induced membrane technique has been well described. However, there are few reports of arthrodesis using this technique. In this case report, we describe a modified Masquelet technique for ankle arthrodesis with nailing. The patient was a 32-year-old man who sustained an open fracture of the right ankle with a substantial osteochondral defect as a result of a fall. Immediately after the injury, a staged procedure using the Masquelet technique was planned. The bone defect was filled with bone cement in the acute stage, but replacement of the cement was needed 6 months after the injury because of a prolonged inflammatory reaction. Ten months after the injury, the bone cement was removed, and ankle arthrodesis was performed using an IM nail with a combination of autologous and artificial bone. As a modification of the Masquelet technique, the anterior surface of the transplant site was covered with a large but thin layer of cortical bone instead of suturing the incised membrane. At 1 year postoperatively, firm bony union was achieved and the implant was removed. At follow-up 3 years after his injury, the patient is able to walk, undertake physical work, and has no clinical signs of infection. Our experience suggests that a modified induced membrane technique may be useful when treating an open limb fracture with an extensive osteochondral defect where preservation of the joint is difficult and arthrodesis is considered., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Complex wounds are commonly thought to require aggressive surgical intervention to achieve healing. However, optimal healing results can often be achieved when greater emphasis is placed on optimizing patient factors prior to any surgical intervention. A retrospective review was performed of pressure ulcers and complex wound cases treated over 5 years at the Yale New Haven Wound Center. Optimal healing including clinical resolution of osteomyelitis and improved scarring was achieved when patient factors, such as glucose control and nutrition, were optimized. Surgical intervention can be more effective and even avoided entirely with the appropriate focus on optimizing patient factors.

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model., Methods: Sixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology., Results: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups., Conclusions: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model., Competing Interests: The authors disclose receiving materials from BoneSupport, but no financial support. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Recommendation: There is a paucity of data regarding total ankle arthroplasty (TAA) in patients with prior infection involving the ankle, whether it be septic arthritis, osteomyelitis, or infection of the surrounding soft tissues. We recommend that patients with prior infections in the affected ankle be worked up for infection, including a thorough history and physical examination, as well as ordering serologic tests and possible aspiration of the joint. During ankle arthroplasty in patients with prior infection, antibiotics should be added to the cement (if used), and the joint should be thoroughly cleansed. Intraoperative cultures of bone and soft tissue should also be obtained., Level of Evidence: Consensus., Delegate Vote: Agree: 100%, Disagree: 0%, Abstain: 0% (Unanimous, Strongest Consensus).

Acromioclavicular joint (ACJ) injury is a common shoulder injury. There are various techniques of ACJ reconstruction. Superficial infection after ACJ reconstruction is not an uncommon complication. However, osteomyelitis post ACJ reconstruction has never been highlighted as a possible complication. Our patient is a 31-year-old male who sustained a Rockwood 5 ACJ dislocation and had anatomical ACJ reconstruction with autogenous gracilis and semitendinosus graft. Our technique involved the anatomical reconstruction of the ACJ and the coracoclavicular ligament with the usage of two bioscrews and the temporary stabilisation of the ACJ with two k-wires. As in any orthopaedic surgery, infection is often disastrous especially when the surgery involves implants. It can be disastrous with high morbidity to the patient as well as a costly complication to treat. Therefore, we wish to highlight this case as despite its rarity, osteomyelitis can be devastating to the patient and should be prevented if possible., (Copyright © 2019 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Pin tract infection in external fixation (ExFix) is a frequent finding which can eventually lead to loosening, osteomyelitis and loss of fixation. Its diagnosis is based on high empiricism and low validity, although it is possible to distinguish between minor and major infection. The first is limited to soft tissues, whereas the latter includes bone involvement. The rate of infection after conversion of external fixation to intramedullary nailing (IMN) is not well known. Unfortunately, papers referring to infection after the conversion of ExFix to intramedullary nailing (IMN) are of evidence level IV or V. It is suggested that conversion of ExFix to IMN should be carried out in a 2 step regimen. The time interval of 2 step regimen is uncertain although some authors have recommended to occur within 9 days. There is no consensus as to which prophylaxis protocol should be applied prior to conversion. In order to throw more light into this important issue, registries capturing important related parameters to the development of infection should be established., (Copyright © 2019. Published by Elsevier Ltd.)

Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono (Debio 1452, AFN-1252), a novel antibiotic in development which targets the staphylococcal enoyl-acyl carrier protein reductase (FabI) and exhibits selective potent antibacterial activity against staphylococcal species, including methicillin-resistant Staphylococcus aureus As part of clinical development in bone and joint infections, a distribution study in bone was performed in 17 patients who underwent elective hip replacement surgery. Patients received 3 doses of 240 mg afabicin orally (every 12 h) at various time points before surgery. Afabicin desphosphono concentrations were measured by liquid chromatography-tandem mass spectrometry in plasma, cortical bone, cancellous bone, bone marrow, soft tissue, and synovial fluid collected during surgery at 2, 4, 6, or 12 h after the third afabicin dose. The study showed good penetration of afabicin desphosphono into bone tissues, with mean area under the curve ratios for cortical bone-, cancellous bone-, bone marrow-, soft tissue-, and synovial fluid-to-total plasma concentrations of 0.21, 0.40, 0.32, 0.35, and 0.61, respectively. When accounting for the free fraction in plasma (2%) and synovial fluid (9.4%), the mean ratio was 2.88, which is indicative of excellent penetration and which showed that the afabicin desphosphono concentration was beyond the MIC 90 of S. aureus over the complete dosing interval. These findings, along with preclinical efficacy data, clinical efficacy data for skin and soft tissue staphylococcal infection, the availability of both intravenous and oral formulations, and potential advantages over broad-spectrum antibiotics for the treatment of staphylococcal bone or joint infections, support the clinical development of afabicin for bone and joint infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02726438.)., (Copyright © 2019 Menetrey et al.)

Introduction: Local delivery of high dose antibiotics in the form of antibiotic impregnated polymethyl methacrylate (PMMA) cement beads or coated rods is commonly used in the management of long bone infections. The downsides of antibiotic cement beads for intramedullary long bone infections are associated with difficulty in removal from the medullary canal, bead breakage, and lack of stability. Antibiotic cement-coated smooth flexible guide wires, rods and nails can have complications such as delamination or debonding of the cement. In addition, the current techniques for cement rod insertion have a risk of iatrogenic joint contamination. To improve upon this technique and decrease potential complications, we propose the use of an antibiotic cement-coated hinged threaded rod as a temporary intramedullary spacer. This technique utilizes both an antegrade and retrograde insertion of the threaded rod into the medullary canal through the bony defect site with connection at the hinge to treat intramedullary long bone infections and infected nonunions., Material and Methods: A total of 40 patients were included in the study. The details in making the cement rod were well documented. The shape of cement rod and the integrity of the cement at the time of rod insertion and rod removal were compared to identify any cement debonding or delamination. Potential postoperative complications including iatrogenic joint infection, displacement or breakage of the threaded cement rods, and fracture displacement were all carefully documented. The preliminary biological effect of the initial debridement and antibiotic cement rod placement was determined using the negative conversion rate of intraoperative cultures., Results: A single antibiotic coated threaded rod was inserted in 18 cases. Two separate antibiotic coated threaded rods were inserted and connected via hinge in 22 cases. There were zero cases of rod breakage and no secondary loss of reduction from antibiotic rod placement to the definitive staged operation. There were zero iatrogenic joint infections. There were zero cases of cement debonding or delamination from the rod. The conversion rate to a negative culture after initial debridement and antibiotic rod placement was 85% (34/40 cases)., Conclusions: The use of an antibiotic coated cement threaded rod with a hinge as an intramedullary spacer provides the benefits of local antibiotic delivery, offers improved construct stability, makes implant removal easier without delamination of the cement mantle, and utilizes the versatility of a hinge to prevent violation of native joints when treating infected nonunions and intramedullary long bone infections., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To present a case that benefited from utilizing hyperbaric oxygen therapy in conjunction with antibiotics for a non-healing mandibular fracture that was highly suspicious of osteomyelitis. Also, to discuss research set forth by Undersea and Hyperbaric Medical Society that supports the use hyperbaric oxygen in such cases., Case: A 25-year-old male status post fist to face resulting in bilateral mandibular fracture. He underwent two surgeries in an attempt to plate the fracture with the assistance of a bone graft. After failure of the bone graft and significant soft tissue wound breakdown, the surgeon was concerned for osteomyelitis and began therapy with intravenous antibiotics and hyperbaric oxygen therapy., Conclusion: The patient completed 30 hyperbaric oxygen treatments and 30 d of intravenous antibiotics. Clinically, the patient responded well and showed healed intraoral wounds and an objective decrease in erythrocyte sedimentation rate over the course of treatment. Unfortunately, on serial imaging the patient showed to have fibrous non-bony union of left fracture site. Even though the patient will need a final definitive plate for his fracture, it will be performed from an extraoral approach with no evidence of underlying infection., (© Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: French reference centers for bone and joint infections (BJI) were implemented from 2009 onwards to improve the management of complex BJIs. This study compared BJI burden before and after the implementation of these reference centers., Patients and Methods: BJI hospital stays were selected from the 2008 and 2013 national hospital discharge database using a validated algorithm, adding the new complex BJI code created in 2011. Epidemiology and economic burden were assessed., Results: BJI prevalence increased in 2013 (70 vs. 54/100,000 in 2008). Characteristics of BJI remained similar between 2008 and 2013: septic arthritis (50%), increasing prevalence with age and sex, case fatality 5%, mean length of stay 17.5 days, rehospitalization 20%. However, device-associated BJIs increased (34 vs. 26%) as well as costs (€421 million vs. €259 in 2008). Similar device-associated BJI characteristics between 2008 and 2013 were: septic arthritis (70%), case fatality (3%), but with more hospitalizations in reference centers (34 vs. 30%) and a higher cost per stay. Among the 7% of coded complex BJIs, the mean length of stay was 22.2 days and mean cost was €11,960., Conclusions: BJI prevalence highly increased in France. Complex BJI prevalence assessment is complicated by the absence of clinical consensus and probable undercoding. A validation of clinical case definition of complex BJI is required., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Bone loss is a common problem in periprosthetic joint infection (PJI) scenarios. Modular megaprosthesis (MP) could offer a limb salvage solution in such situations. Concerns about risk of infection relapse, reinfection and implant longevity exist regarding MP use in cases of chronic PJI, rather than standard implants. We therefore sought to analyze our results with MP use in chronic PJI cases., Methods: We performed a retrospective analysis of 29 MP patients. Inclusion criteria were the use of this type of modular megaimplant for reconstruction of segmental bone defects in chronically infected lower-extremity arthroplasties (hip or knee) and a minimum follow-up of 18 months. We evaluated the primary outcome of infection control or recurrence. The MPs were classified into 3 groups, according the bone segment replaced (proximal femur, distal femur or total femur). We further analyzed complications, pain, patient satisfaction and functional results., Results: Mean age was 75 years; mean follow-up was 48 months (range 18-82). The most frequently involved pathogens were coagulase-negative staphylococci (62%). Polymicrobial infection was detected in 7 patients. Twenty-eight patients were managed with a two-stage approach. The infection-free rate at the end of follow-up was 82.8% (24 of 29 patients). Aside from infection relapse, the most frequent complication was dislocation. Final-point survival rate was 91.2% (CI 68.1-97.8). Clinical outcome data and satisfaction results were acceptable., Conclusion: According our data, MP is a useful tool in treating end-stage PJI cases, achieving acceptable eradication, satisfaction and implant survivorship rates.

In this study, electrolytically deposited strongly adherent silver nanoparticles on stainless-steel (SS) implants were used for in situ osteomyelitis treatment. Samples were heat treated to enhance adhesion of silver on 316 L SS. Ex vivo studies were performed to measure silver-release profiles from the 316 L SS screws inserted in equine cadaver bones. No change in the release profiles of silver ions were observed in vitro between the implanted screws and the control. In vivo studies were performed using osteomyelitic rabbit model with 3 mm diameter silver-deposited 316 L SS pins at two different doses of silver: high and low. Infection control ability of the pins for treating osteomyelitis in a rabbit model was measured using bacteriologic, radiographic, histological, and scanning electron microscopic studies. Silver-coated pins, especially high dose, offered a promising result to treat infection in animal osteomyelitis model without any toxicity to major organs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1073-1083, 2018., (© 2017 Wiley Periodicals, Inc.)

Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. Eighty-six patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p = 0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p = 0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads., (© 2018 by the Wound Healing Society.)

If a bone or joint infection is suspected, perioperative antibiotic prophylaxis is frequently withheld until intraoperative microbiological sampling has been performed. This practice builds upon the hypothesis that perioperative antibiotics could render culture results negative and thus impede tailored antibiotic treatment of infections. We aimed to assess the influence of antibiotic prophylaxis within 30 to 60 min before surgery on time to positivity of microbiological samples and on proportion of positive samples in Cutibacterium acnes bone and joint infections. Patients with at least one sample positive for C. acnes between January 2005 and December 2015 were included and classified as having an "infection" if at least 2 samples were positive; otherwise they were considered to have a sample "contamination." Kaplan-Meier curves were used to illustrate time to culture positivity. We found 64 cases with a C. acnes infection and 46 classified as having a C. acnes contamination. Application of perioperative prophylaxis significantly differed between the infection and contamination groups (72.8% versus 55.8%; P < 0.001). Within the infection group, we found no difference in time to positivity between those who had or had not received a perioperative prophylaxis (7.07 days; 95% confidence interval [CI], 6.4 to 7.7, versus 7.11 days; 95% CI, 6.8 to 7.5; P = 0.3). Also, there was no association between the proportion of sample positivity and the application of perioperative prophylaxis (71.6% versus 65.9%; P = 0.39). Since perioperative prophylaxis did not negatively influence the microbiological yield in C. acnes infections, antibiotic prophylaxis can be routinely given to avoid surgical site infections., (Copyright © 2018 American Society for Microbiology.)

Background: Treatment of bone infection is difficult due the systemic administration of antibiotics, which means that only low concentrations reach the inflamed bone tissue. Loss of bone stock is common in osteomyelitis and device associated infection. Local antibiotics are administered in several ways for prophylactic purposes and also for treatment of bone infection. We intend to show the options and limitations of clinical use of antibiotic-loaded bone grafts., Suitability: Bone grafts are a suitable carrier system for antibiotics. Bone grafts may be loaded with a variety of antimicrobial agents so that individual therapies may be carried out. Critical systemic side effects are unlikely even though extreme high drug concentrations are obtained locally, if the thresholds for loading with antibiotics are respected. Thus, antibiotic-loaded bone grafts are appropriate for prophylaxis and therapy as well. If processing is done in the operating theatre compliance to the legal rules must be respected., Rules: Due to a lack of standardised procedures for loading, application and performance of the application of antibiotic-loaded bone grafts medical societies are being asked to initiate consensus meetings in order to issue recommendations or guidelines with respect to antibiotic-loaded bone grafts to establish reliable rules for surgeons using these devices.

Multifunctional-therapeutic three-dimensional (3D) scaffolds have been prepared. These biomaterials are able to destroy the S. aureus bacterial biofilm and to allow bone regeneration at the same time. The present study is focused on the design of pH sensitive 3D hierarchical meso-macroporous 3D scaffolds based on MGHA nanocomposite formed by a mesostructured glassy network with embedded hydroxyapatite nanoparticles, whose mesopores have been loaded with levofloxacin (Levo) as antibacterial agent. These 3D platforms exhibit controlled and pH-dependent Levo release, sustained over time at physiological pH (7.4) and notably increased at infection pH (6.7 and 5.5), which is due to the different interaction rate between diverse Levo species and the silica matrix. These 3D systems are able to inhibit the S. aureus growth and to destroy the bacterial biofilm without cytotoxic effects on human osteoblasts and allowing an adequate colonization and differentiation of preosteoblastic cells on their surface. These findings suggest promising applications of these hierarchical MGHA nanocomposite 3D scaffolds for the treatment and prevention of bone infection., Statement of Significance: Multifunctional 3D nanocomposite scaffolds with the ability for loading and sustained delivery of an antimicrobial agent, to eliminate and prevent bone infection and at the same time to contribute to bone regeneration process without cytotoxic effects on the surrounding tissue has been proposed. These 3D scaffolds exhibit a sustained levofloxacin delivery at physiological pH (pH 7.4), which increasing notably when pH decreases to characteristic values of bone infection process (pH 6.7 and pH 5.5). In vitro competitive assays between preosteoblastic and bacteria onto the 3D scaffold surface demonstrated an adequate osteoblast colonization in entire scaffold surface together with the ability to eliminate bacteria contamination., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period., Methods: We identified patients ≤18 years old with pneumococcal OAI at 8 children's hospitals in the United States (2000-2015). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory., Results: We identified 97 (3.3%) patients with pneumococcal OAI out of 2943 patients with IPD. Over 60% of the children were <2 years old. Septic arthritis (56.7%, 55/97) was the most common pneumococcal OAI, followed by osteomyelitis (25.8%, 25/97) and septic arthritis with concomitant osteomyelitis (17.5%, 17/97). Hospitalization for pneumococcal OAI overall decreased from 6.8 [95% confidence interval (CI): 5.2-8.6] to 4.4 (95% CI: 3.0-6.3) per 100,000 admissions from 2000-2009 to 2010-2015 (-35%, P = 0.05). Hospitalization for pneumococcal OAI caused by PCV13 serotypes decreased from 4.6 (95% CI: 3.4-6.2) to 0.9 (95% CI: 0.3-1.9) per 100,000 admissions from 2000-2009 to 2010-2015 (-87%, P < 0.0001). Overall, 12% of isolates had a penicillin minimal inhibitory concentration> 2 µg/mL, 3% a ceftriaxone minimal inhibitory concentration> 1 µg/mL and 15% were clindamycin resistant; these proportions remained unchanged after the introduction of PCV13. Serotypes 19A and 35B were responsible for penicillin and ceftriaxone nonsusceptible isolates in 2010-2015., Conclusions: Pneumococcal OAI represents 3% of all IPD, affecting mainly healthy infants and young children. Hospitalization for pneumococcal OAI caused by PCV13 serotypes dramatically decreased (-87%) after the introduction of PCV13.

Background: We examined combat-related open extremity fracture infections as a function of whether posttrauma antimicrobial prophylaxis included expanded Gram-negative (EGN) coverage., Methods: Military personnel with open extremity fractures sustained in Iraq and Afghanistan (2009-2014) who transferred to participating hospitals in the United States were assessed. The analysis was restricted to patients with a U.S. hospitalization period of ≥7 days. Prophylaxis was classified as narrow (e.g., IV cefazolin, clindamycin, and/or amoxicillin-clavulanate) or EGN, if the prophylactic regimen included fluoroquinolones and/or aminoglycosides., Results: The study population included 1,044 patients, of which 585 (56%) and 459 (44%) received narrow and EGN coverage, respectively (p < 0.001). Skin and soft-tissue infections (SSTIs) were more common among patients who received narrow prophylaxis compared to EGN coverage (28% vs. 22%; p = 0.029), whereas osteomyelitis rates were comparable between regimens (8%). Similar findings were noted when endpoints were measured at 2 and 4 weeks postinjury. There was no significant difference related to length of hospitalization between narrow and EGN regimens (median: 34 and 32 days, respectively) or operating room visits (median: 5 and 4). A higher proportion of EGN coverage patients had Gram-negative organisms isolated that were not susceptible to fluoroquinolones and/or aminoglycosides (49% vs. 40%; p < 0.001). In a Cox proportional model, narrow prophylaxis was independently associated with an increased risk of extremity SSTIs (hazard ratio: 1.41; 95% confidence interval: 1.09-1.83)., Discussion: Despite seeing a small benefit with EGN coverage related to a reduction of SSTIs, it does not decrease the risk of osteomyelitis, and there seems to be a cost of increased antibiotic resistance associated with use. Overall, our findings support the current post-combat trauma antibiotic prophylaxis guidelines, which recommend the use of cefazolin or clindamycin with open fractures., Level of Evidence: Prognostic/Epidemiological, Level II; Therapy, level IV.

Despite the improvement of surgical techniques surgical site infections (SSIs) still remain clinically challenging in high risk patients undergoing osteosynthesis for tibia fractures. The use of an antibiotic coated implant might reduce the adhesion of bacteria on the implant surface and could therefore reduce the rate of implant-related infection or osteomyelitis. A gentamicin-coated tibia nail was evaluated in a prospective study. Four centers enrolled 100 patients (99 treated) with fresh open or closed tibia fractures, or for non-union revision surgery and followed them for 18 months. Data collected included infection events, radiographs, SF-12, EQ-5D, Iowa Ankle score, and the WOMAC questionnaire. Sixty-eight of the 99 treated patients suffered from a fresh fracture, while in 31 patients, the intramedullary nail was implanted for revision purposes, including non-unions due to infection. Fifteen (22%) of the fresh fractures were GA Type III. The follow-up rate was 87% and 82% at 12 months and 18 months, respectively. Deep surgical site infections occurred in 3 fresh fractures and two in revision surgeries. We did not observe any local or systemic toxic effects related to gentamicin during this study. The use of the antibiotic coated nail is an option in patients with a high infection risk, like open factures or infected non unions, in the prevention of the onset of an implant-related infection or osteomyelitis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections., Methods: Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed., Results: The most appropriate handling and mechanical properties (Young's modulus, E = 92 ± 4 MPa and breaking force, F MAX  = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F MAX  = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced., Conclusions: GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.

Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G) through in vivo study in rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G), nanotubular anodized titanium uncoated with gentamicin (NTATi) and titanium uncoated with gentamicin (Ti). The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively ( P <0.05). Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively ( P <0.01). The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti groups., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Open physeal fractures of the distal phalanx of the hallux are the lesser described counterpart to the same fracture of the finger, known by its eponym as a "Seymour fracture". Displaced Salter-Harris phalangeal fractures present with a concomitant nailbed or soft tissue injury. Often these fractures occur in the summer months when open-toe footwear can be worn, however, they may occur indoors as well. Frequently, the injury results from direct axial load of the toe, or "stubbing", which causes the fracture and associated soft tissue injury. Prompt diagnosis and appropriate treatment is necessary to prevent negative sequelae such as osteomyelitis, malunion, nonunion, or premature growth arrest. In this article, we present a 12year-old male who sustained an open physeal fracture of the distal phalanx when he "stubbed" his great toe on a bed post. His injury was initially misdiagnosed at an urgent care facility, thereby delaying appropriate intervention and necessitating an operative surgical procedure. Additionally, we review the existing literature discussing these infrequently reported injuries, as well as present key points as they pertain to the diagnosis and management of this injury in the emergency department., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To review the outcomes of patients treated with the Ilizarov method for an isolated, closed, simple diaphyseal, Tibial fracture at our institution over the last decade., Methods: The Ilizarov frame database was used to identify 76 skeletally mature patients who sustained an isolated, closed, extra-articular, simple, diaphyseal Tibial fracture; the injury also known as a "nail-able Tibial fracture.", Results: The average age of the patient was 38 (17-70). All 76 patients progressed to union. The average time until union was 148 (55-398) days. The coronal and sagittal alignment was 3° (0-17°) and 4° (0-14°) respectively. No patient suffered from compartment syndrome. No patient developed septic arthritis. No patient had documented anterior knee pain or secondary knee specialist input post frame removal. On average, there were 9(4-29) follow up appointments and 10(5-26) radiographs post frame application. There is a 59% chance of a patient having a difficulty post frame application. The malunion rate was 5%. Persisting pinsite infection post frame removal occurred in 5 patients (6.5%). Drilling of the pinsite sequestrum resolved the infection in four of these patients, giving a deep infection rate of 1.3%., Conclusions: The Ilizarov method has a role to play in the treatment of simple closed Tibial shaft fractures in patients who need to kneel. Patient education is a priority however; the patient must be made aware of the difficulty rate associated with the Ilizarov method when compared to the complication profile of alternative treatments., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Background: We investigated the clinical effectiveness of antimicrobial prophylaxis in lower-extremity open fractures following the Eastern Association for the Surgery of Trauma Guidelines., Methods: This observational, retrospective, single-center study included adults with lower-extremity open fractures of the ankle, tibia, fibula, or femur. The primary endpoint was the incidence of osteomyelitis within 12 months of the fracture. Secondary endpoint comparisons were the time of antibiotic initiation and drug selection., Results: A total of 90 patients were included. Patients suffered from Gustilo and Anderson grades I (14%), II (54.7%), and III (31.3%) fractures. Almost all patients received cefazolin (98%). Among grade III fractures, 59.3% (16/27) of patients received additional gram-negative coverage as recommended by the guidelines. The osteomyelitis rate was 8.9%. There was no difference in osteomyelitis rates among patients with grade III fractures who received or did not receive additional gram-negative coverage: 18.8% (3/16) and 0 (0/11) (p = 0.248), respectively. There was no correlation between median antibiotic start time or antibiotic stop time after closure and the development of osteomyelitis, respectively. Resistant organisms caused 50% (4/8) of the osteomyelitis cases. On univariate analysis, obesity had the most significant association with osteomyelitis (p = 0.026)., Conclusions: Bacterial resistance was common among cases of osteomyelitis in our cohort. Obesity was associated with a higher rate of osteomyelitis.

Background/aim: Staphylococcus aureus infection associated with orthopedic implants cannot always be controlled. We used a knee prosthesis model with implant-related osteomyelitis in rats to explore induction of an effective immune response with active and passive immunization., Materials and Methods: Fifty-two Sprague-Dawley rats were divided into active (N=28) and passive immunization groups (N=24). A bacterial inoculum of 10 3 S. aureus MN8 was injected into the tibia and the femur marrow before insertion of a non-constrained knee prosthesis in each rat. The active-immunization group received a synthetic oligosaccharide of polysaccharide poly-N-acetylglucosamine (PNAG), 9G1cNH 2 and the passive-immunization group received immunization with immunoglobulin from rabbits infected with S. aureus., Results/conclusion: Active immunization against PNAG significantly reduced the consequences of osteomyelitis infection from PNAG-producing intercellular adhesion (ica + ) but not ica - S. aureus. Passive immunization resulted in better clinical assessments in animals challenged with either ica + or ica - S. aureus, suggesting a lack of specificity in this antiserum., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Biofilms are a major aetiological factor in many infections. Bacteria growing within a biofilm are extremely resilient to standard antimicrobials; biofilm-associated infections are thus challenging to treat. Understanding how and why biofilms form can improve prevention and management of biofilm infections.