Locally delivered adjuvant biofilm-penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection.

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.

Local transplantation of bone marrow concentrated granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect.

PURPOSE: Infected, long bone non-unions present a significant clinical challenge. New and alternative therapies are needed to address this problem. The purposes of this study were to compare the number of circulating granulocyte-macrophage colony-forming units (CFU-GM) in the peripheral blood of polytraumatic patients with infected tibial non-unions and in the peripheral blood of control patients with the hypothesis that their number was decreased in polytraumatic patients; and to treat their infection without antibiotics and with local transplantation of bone marrow concentrated granulocytes precursors. METHODS: Thirty (18 atrophic and 12 hyperthrophic ) infected tibial non-unions (without bone defect) that occurred after open fractures in polytraumatic patients were treated without antibiotics and with percutaneous injection of autologous bone marrow concentrate (BMC) containing granulocytes precursors (CFU-GM). CFU-GM progenitors were assessed in the bone marrow aspirate, peripheral blood, and fracture site of these patients. The number of these progenitors was compared with the CFU-GM progenitors of control patient samples (healthy donors matched for age and gender). Outcome measures were: timing of union, callus formation (radiographs and CT scan), and recurrence of clinical infection. RESULTS: As compared to control patients, the number of CFU GM derived colonies was lower at peripheral blood in patients with infected nonunions. The bone marrow graft injected in nonunions contained after concentration 42 621 ± 20 350 CFU-GM-derived colonies/cc. Healing and cure of infection was observed at six months for 25 patients and at one year follow up for 30 patients. At the median ten year follow-up (range: 5 to 15), only one patient had clinical recurrent infection after healing (between 6 months and last follow-up). CONCLUSION: The peripheral blood of these polytraumatic patients with infected nonunions had a remarkable decrease in CFU-GM-derived colonies as compared with normal controls. Local transplantation of concentrated CFU-GM-derived colonies aspirated from bone marrow allowed cure of infection and healing without antibiotics.

Bacterial contamination of open fractures - pathogens, antibiotic resistances and therapeutic regimes in four hospitals of the trauma network Cologne, Germany.

INTRODUCTION: The bacterial contamination of soft tissues and bone in open fractures leads to an infection rate of up to 50%. Pathogens and their resistance against therapeutic agents change with time and vary in different regions. In this work, our aims were to characterize the bacterial spectrum present in open fractures, analyze the bacterial resistance to antibiotic agents and question the EAST guideline recommendations for antibiotic prophylaxis after open fractures in a German Trauma Network. MATERIALS AND METHODS: We conducted a retrospective cohort study and included all patients with open fractures from 1(st) of January 2011 until the 31(st) of December 2014 in four hospitals of the trauma network cologne. Soft tissue damage was classified according to the Gustilo Anderson classification. RESULTS: We included 123 patients. Forty-five injuries (37%) were classified I°, 45 (37%) as II° and 33 (27%) as III°. Lower leg (34%) was the most commonly injured location. An antibiotic prophylaxis was administered to 109 patients (89%). In 107 of them (98%) a cephalosporin or cephalosporin combination was given. In 35 of the patients (28%), microbiological samples were taken of the fracture site. Wound cultures were positive in 21 patients (60%). Fifty percent of the bacterial detections occurred in III° fractures. Coagulase negative Staphylococci (COST) were the most frequent pathogens. In II° open fractures one gram-negative strain was isolated. Fewest resistances were seen against quinolones and co-trimoxazole. DISCUSSION: The recommended EAST guideline prophylaxis would have covered all but one bacterium (97% of positive cultures). One Escherichia coli was found in a II° open fracture and would have been missed. One of the isolated Staphylococci epidermidis and an Enterococcus faecium were resistant against gentamycin and first- and second-generation-cephalosporin's which were used as prophylaxis frequently. However, a regional adaption of the EAST guidelines seems not justified due to the rather low number of cases in our study. CONCLUSION: The EAST guideline seems to be adequate in a high percentage of cases (97%) in the setting of the trauma network cologne. Further research should be guided at identification of initial open fracture pathogens to improve the efficiency of antibiotic prophylaxis.

Hyperbaric Oxygen in Lower Limb Trauma (HOLLT); protocol for a randomised controlled trial.

INTRODUCTION: Open fractures with significant soft tissue injury are associated with high rates of complications, such as non-union, infection, chronic pain and disability. Complications often require further inpatient care, and in many cases, multiple operations and prolonged rehabilitation. Use of hyperbaric oxygen therapy as an adjunct to standard orthopaedic trauma care has the potential to reduce the complications of musculoskeletal injury and thus improve outcomes. Two previous randomised trials have suggested some positive effect, but neither functional measures nor long-term outcomes were reported. METHODS AND ANALYSIS: An international, multicentre, randomised, open-label, clinical trial. Patients with trauma with an acute open fracture of the tibia with severe soft tissue injury (Gustilo grade 3) and high risk of injury-related complications were recruited from participating major trauma hospitals with hyperbaric facilities. Patients were enrolled with the expectation of commencing 12 sessions of hyperbaric oxygen therapy within 48 h of injury. The primary outcome measure is the incidence of acute complications of the open fracture wound at 14 days. Other short-term outcome measures include amputation, need for fasciotomy, time until wound closure, breakdown of closed wounds, time until definitive orthopaedic fixation, number of operative procedures, intensive care stay and hospital stay. Long-term follow-up will continue for 2 years postinjury. ETHICS AND DISSEMINATION: Ethics approval was given by The Alfred Health Human Ethics Committee (206/04) and the Monash University Human Research Ethics Committee (CF07/4208). Approval was also obtained from the institutional research ethics committee at each participating site. This study will make a significant contribution to the trauma literature and should answer the question of whether hyperbaric oxygen therapy can significantly improve outcomes in severe lower limb trauma. Collective study results will be published in international journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT00264511; Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12607000559415.

Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been adopted for crush injuries, but there are few studies supporting its use. We therefore investigated the effects of HBO2 on management of patients with complicated crush injuries. METHODS: This historic cohort study included patients with crush injuries and open fractures with severities greater than or equal to Gustilo class IIIA. We divided the patients into two groups: Control and HBO2. The control group received conventional treatment, while the HBO2 group received conventional treatment plus HBO2. We compared the groups with respect to the incidence of infection, need for additional surgery, and length of intensive care unit (ICU) and hospital stays. RESULTS: There were 16 patients in the HBO2 group and 13 in the control group. There were no patients with infections in the HBO2 group, whereas in the control group six patients had infections and five needed another drainage procedure. These incidences were significantly lower in the HBO2 group (p = 0.003 and 0.013). However, the durations of ICU and hospital stays were similar across the two groups. CONCLUSIONS: HBO2 is effective in the management of crush injuries from the viewpoint of reducing complications and reoperations. These observations should be verified in additional studies with larger sample sizes because the patient number is limited.

Acute compartment syndrome after open forearm fracture--scale of the problem and case report.

Acute compartment syndrome is caused due to a sudden increase in the tissue pressure in a given fascial compartment. Missed and undiagnosed or not treated in time can lead to irreversible damage to limb muscles and nerves due to ischemia mechanism. This paper presents a case of a patient with an open forearm fracture treated conservatively in plaster.

Thalidomide prolongs survival after experimental musculoskeletal injury, through an effect on mononuclear apoptosis.

BACKGROUND: This study was conducted to investigate the effects of intravenous thalidomide administration in an experimental model of musculoskeletal trauma. We hypothesized that because thalidomide inhibits secretion of tumor necrosis factor alpha (TNF-α), survival of animals that received thalidomide would be significantly prolonged. MATERIAL AND METHODS: After an open fracture of the right femur, 24 rabbits were randomly assigned to control and thalidomide groups. Intravenous therapy with thalidomide was started 30 min after fracture. Hemodynamic monitoring of all animals was performed for 4 h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-α measurement and for isolation of peripheral blood mononuclear cells (PBMCs). Apoptosis of PBMCs was measured by flow cytometry. RESULTS: Survival was significantly prolonged in the thalidomide group. Apoptosis of PBMCs was increased in the control group compared with the thalidomide group at 24 h. There were no differences in vital signs, blood and tissue cultures, and serum TNF-α concentration between the two groups. CONCLUSIONS: Intravenous thalidomide prolonged survival in an experimental model of severe musculoskeletal injury in rabbits. Its mechanism of action did not involve TNF-α suppression but prevention of mononuclear apoptosis. In view of these promising results, further research is needed to clarify the immunomodulatory mechanism of action of thalidomide and its potential use for the management of severe trauma.

Antibiotic-impregnated calcium sulfate use in combat-related open fractures.

This article presents our experience with the use of antibiotic-impregnated calcium sulfate in the management of comminuted open fractures with a bony defect caused by combat-related blast injuries and high-energy wounds. Calcium sulfate was used 19 times in 15 patients (17 fractures) as a bone graft substitute and a carrier for antibiotics. The anatomic sites of the graft were as follows: 6 calcanei, 1 midfoot, 1 metatarsal, 5 tibiae, 3 femorae, and 1 humerus. The average number of procedures prior to grafting was 6.2 (range, 2-10; median, 6) with grafting performed at an average 28 days after injury (range, 9-194 days; median, 14 days). Average radiographic follow-up of 12 fractures not requiring repeat grafting or amputation was 8.5 months (range 1-19 months; median, 7 months), and all of these fractures demonstrated clinical and radiographic evidence of fracture healing and consolidation. Four patients subsequently underwent 5 transtibial amputations: 2 for persistent infection, 1 when the patient changed his mind against limb salvage acutely, and 2 for severe neurogenic pain. Including the 2 amputations for persistent infection, 4 patients (22.2%) required further surgical management of infection. Three patients (17.6%) subsequently developed heterotopic ossification at the graft site, which required surgical excision. Antibiotic-impregnated calcium sulfate is effective in treating severe, contaminated open fractures by reducing infection and assisting with fracture union.

Resolución de una complicación de herida grave de miembro inferior: a propósito de un caso / Resolution of a severe complication of lower limb injury: a propos of a case

Se presenta una sucesión de complicaciones, en el marco terapéutico de una lesión grave de miembro inferior. Se muestra la resolución de cada una de ellas, con la revaloración de la situación en los intervalos entre complicaciones. Diferentes lesiones necesitan diferentes coberturas: estas necesidades deben ser solucionadas de la mejor forma posible, más allá de su complejidad, y esto sólo se puede lograr manejando todas las variantes y técnicas de reconstrucción. Es también muy importante en el diseño del plan no alterar estructuras que podrían ser útiles, como rescate, en caso de no se exitosa la opción implementada. El apoyo durante el plan terapéutico de técnicas complementarias, como la terapia VAC y la cámara hiperbárica, en nuestro paciente fueron fundamentales; creemos que deben ser tenidas en cuenta como una herramienta más para el manejo de esta patología. Una de las características del protocolo de manejo interdisciplinario es el diálogo permanente entre los servicios de Traumatología y Cirugía Plástica y éste es el elemento que permite flexibilizar la terapéutica frente a cada caso particular.

Use of external fixation and primary wound closure in an open comminuted first metatarsal fracture: a case report.

Management of open, comminuted fractures presents a challenge for the foot and ankle surgeon. Reconstructive surgery for such injuries has a high potential for the development of serious complications, and factors such as the extent of soft tissue injury, neurovascular status to the foot, and fracture stability must be taken into consideration before determining a surgical plan. This article describes the case of a patient who presented with an open, comminuted first metatarsal fracture as a result of a chainsaw injury. The patient was treated with a uniplanar mini-external fixator, demineralized bone matrix, primary wound closure, and external bone growth stimulation. At 1-year follow-up, the interview and examination revealed the patient to be pain free with a functional first ray. ACFAS Level of Clinical Evidence: 4.

[Hyperbaric oxygenation in the treatment regimen using Ilizarov technique in patients with open fractures]. / Giperbaricheskaia oksigenatsiia v sisteme lecheniia po metodu Ilizarova bol'nykh s otkrytymi perelomami.

The dynamics of clinico-physiological parameters in complex treatment of patients with open fractures of the extremities using hyperbaric oxygenation was analyzed in 22 patients with severe injuries with different degree of ischemia of the extremity, and 9 patients with scanty injuries of the soft tissues. It was shown that vasospasm was observed in patients with the initially normal microcirculation after a course of HBO treatment. In patients with no or initially low capillary blood flow the microcirculation was enlarged due to vasodilatation of the arterioles. No considerable effects of the course of HBO on the main blood flow was revealed. Recommendations are given on using the HBO therapy in management of patients with severe open fractures and osteosynthesis of the injured segment by the Ilizarov methods.

Emotional impairment after right orbitofrontal lesion in a patient without cognitive deficits.

The present study describes a patient, M.L., with right orbitofrontal lesion, who showed no impairment on main neuropsychological tests, including those measuring frontal functions. Nevertheless, he had deeply affected emotional responses. In line with Damasio's work, the patient had lower skin conductance during the projection of a standardized set of emotional slides. Furthermore, he showed altered facial expressions to unpleasant emotions, displaying low corrugator supercilii electromyographical activity associated with reduced recall of unpleasant stimuli. During a task focusing on imagery of emotional situations, M.L.'s heart rate and skin conductance responses were affected during both pleasant and unpleasant conditions. Facial expressions to unpleasant imagery scripts were also impaired. Thus, the orbitofrontal cortex proved to play a critical role in retrieval of psychophysiological emotional patterns, particularly to unpleasant material. These results provide the first evidence that orbitofrontal lesions are associated with emotional impairment at several psychophysiological levels.

Choice and duration of antibiotics in open fractures.

Open fracture wounds are contaminated wounds, and wide spectrum antibiotic therapy effective against both gram-positive and gram-negative organisms is recommended. Combination therapy has been shown to be effective in significantly reducing the infection rate in open fractures. For type I and II open fracture wounds, 3 days of antimicrobial therapy is recommended; for type III open fracture wounds, 5 days of treatment is recommended. When secondary procedures are performed, such as bone grafting, open reduction and internal fixation, soft tissue transfers, and other procedures involving the fracture site, an additional 72 hours of therapy is recommended. When antibiotic therapy is given after the initial period, antimicrobials administered should be selected on the basis of the culture and sensitivities of the original infecting organisms.

Gas gangrene following compound fractures

The authors report on the management of 4 cases of gangrene. These cases are presented to remind clinicians of the possibility of this complication following compound injuries. Two cases were treated with hyperbaric oxygen. The importance of keen index of suspicion in the early diagnosis of gas gangrene together with the use of hyperbaric oxygen in cases of spreading myositis negates the need for mutilating surgery. (AU)

Use of ofloxacin in open fractures and in the treatment of post-traumatic osteomyelitis.

In two open prospective studies, the efficacy and tolerance of ofloxacin in the prevention of infection in patients with open fractures (n = 58) and in the treatment of chronic post-traumatic osteomyelitis (n = 115) were examined. In the study with open fractures, bone and/or soft tissue infection occurred in only four cases (6.5%). During an observation period of at least 12 months, post-traumatic osteomyelitis was seen in two patients with III degree open fractures (9%), while in the groups with I degree and II degree open fractures no bone infection could be found. Therefore, the rate of post-traumatic osteomyelitis related to all patients was 3.3%. In the second study with 115 patients suffering from chronic post-traumatic osteomyelitis 141 different Gram-positive and Gram-negative pathogens were isolated. 73% were Gram-positive cocci with Staphylococcus aureus in more than 50% of the cases. An elimination rate of more than 90% was found in the Gram-positive and Gram-negative bacteria, leading to a clinical cure in 85% and a recurrence of infection in 5% of the cases. The tolerability of ofloxacin was excellent. No drug-related allergic reactions were observed. Diarrhoea and headache occurred in less than 2% of patients. With adequate surgical treatment, ofloxacin proved to be a useful antimicrobial agent in the prevention and therapy of bone infection.

Treatment of recalcitrant non-union with a capacitively coupled electrical field. A preliminary report.

Twenty-two well established non-unions in twenty patients were treated with a capacitively coupled electrical signal (sine wave, sixty kilohertz, five volts peak to peak) that was applied non-invasively through stainless-steel capacitor plates placed on the skin surface overlying the approximate site of the non-union. The average age of the eleven female and nine male patients in this series was 38.4 years, and the average duration of the twenty-two non-unions was 3.3 years. Seventeen of the non-unions were labeled recalcitrant, meaning that they had failed to heal after either previous bone-grafting or another type of electrical stimulation, or both. Five of the non-unions had not been previously treated. Seventeen (77.3 per cent) of the non-unions achieved solid osseous union after an average of 22.5 weeks of treatment with capacitive coupling. The results in this small series were not affected by the non-union being recalcitrant, by the fact that one patient bore full weight on the extremity in a cast, by the presence of osteomyelitis, or by the presence of remaining metallic internal-fixation devices in the bone. Since capacitive coupling is non-invasive, involves portable equipment, allows full weight-bearing on the lower extremity in a cast, is easy to apply, and does not require precise localization of the capacitor plates, it has distinct advantages over other methods of treating non-union with electricity.