Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Aim. Antibiotic-eluting calcium compounds can be used to deliver antibiotics in the management of prosthetic joint infection (PJI). Described omplications include wound drainage, heterotopic ossification(HO) as well as hypercalcaemia which is potentially life threatening. The aim of this study is to assess the incidence of hypercalcaemia and other complications between two calcium based antibiotic delivery systems. Method. A retrospective study was performed. Thirty two patients treated with Stimulan or Cerament Calcium based antibiotic delivery system between August 2014 to January 2017 were included. Seven patients received Cerament, 21 cases received Stimulan and one patient received both. The volume used as well as pre- and post-operative serum calcium were recorded as well as any wound related complications and radiologic changes suggestive of heterotopic ossification. The postoperative serum adjusted Calcium were taken weekly during the initial post operative period. Patients with overactive parathyroid disease and pre-existing renal disease were excluded. Results. Stimulan group (n=22, Mean volume 39.2ml). Mean pre-operative serum calcium was 2.48mmol/l. At 1 and 2 weeks post-surgery mean levels were 2.51 and 2.47mmol/l (patients receiving <40ml), and 2.47 and 2.50mmol/l (patients receiving >40ml – 9 cases) respectively. There was no significant difference between pre/post-operative levels at 1 (p=0.97) or 2 weeks (p=0.91) and no difference between those treated with <40ml or >40ml of Stimulan at 1 or 2 weeks (p=0.91). Cerament group (n=8, Mean volume 9.4ml). Mean pre-operative serum calcium was 2.42mmol/l. Mean post-operative levels at 1 and 2 weeks post-surgery were 2.44mmol/l (p=0.92) and 2.37mmol/l (p=0.61) respectively. One patient had prolonged wound discharge and required re operation. No HO was encountered. Conclusions. Our results suggest that hypercalcaemia and other complications are uncommon with the use calcium based antibiotic delivery systems and that calcium based antibiotic delivery systems are safe in the treatment of PJI

Bone infection occurring after fractures or orthopedic surgery can progress to the chronic stage and lead to poor results of treatment. Optimal treatment of chronic osteomyelitis are stabilization the fracture, biological recovery of bone defects and destroy bacterial infection. Traditional methods of treatment are systemic administration of antibiotics and surgical treatment of active infection focus. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. The aim of this investigation was to study the results of the complex treatment of patients with chronic osteomyelitis using biodegradable nanomaterials “PerOssal” as antibiotic delivery system. The study was performed at Regional center traumatology and orthopedics, Karaganda, Kazakhstan. A total 20 patient with post-traumatic/post-operative osteomyelitis were included in this open-label, prospective study. Bacteriological examination was taken with the determination of culture and sensitivity test preoperatively, during and postoperatively. After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal which can be loaded with different antibiotics depending from the antibiotic sensitivity test. Postoperative wound is completely was sutured. Systemic antibiotic treatment are allowed. The course of infection was monitored by determination leukocyte count and blood sedimentation rate; blood samples were taken befor, 24 hours after surgery, and on days 3, 7, 10, 14. Wound healing was assessed on days 2, 3, 7, 10, and at the time of removal of sutures. Resorption of implanted beads and bone reconstruction were evaluated by X-ray at after operation and at approximately one, three and six months after implantation. A total of 20 patients (mean age 38,1 (26 to 53), 14 male, 6 female) were treated with Perossal pellets (AAP, Germany) from October 2013 to April 2015. Mean leukocyte counts and blood sedimentation rate were within the normal laboratory range and did not indicate infectious complications during the first 21 days after surgery. Primary wound healing occurred in 18 patients and secondary wound healing in two patients. There were two cases of re-infection during the course of the study, one of them related to an incomplete eradication of infected tissue and multidrug-resistant strain occurring during the course of the study, the other is occurred that patient non-compliance. Radiographic analysis six months after surgery showed progressive resorption of the implanted pellets, but only 10 cases have decreasing size of defects on X-ray. This study in adult patients with chronic post-traumatic/post-operative osteomyelitis demonstrated that these biodegradable bone filler pellets which can be loaded with different antibiotics are a clinically useful local antibiotic delivery system and bone substitute which can be used as an alternative to other anti-infective implants. The implantation of the pellets was safety and well tolerated in all patients. This composite can provide adequate protection against bacterial infection during the first weeks after implantation and to support the bone healing process

Background. The different biodegradable local antibiotic delivery systems are widely used in recent years. The aim of this study was to evaluate the bactericidal activity antibiotic loaded PerOssal pellet in vitro and its effectiveness in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Material and methods. MALDI-TOF have been applied to microbiological diagnosis in patient with osteomyelitis. In most cases, Staphylococcus aureus was isolated. In vitro Ceftriaxone-Loaded PerOssal pellet were placed in middle agar plate containing a stock strain of Staphylococcus aureus. Plates were incubated at 37ºC for 24 hours. The zones of bacterial inhibition were recorded after 24, 48 and 72 hours of incubation. In vivo evaluation was performed by prospectively studying of 21 patients with a clinically and bacteriologically diagnosed Staphylococcus aureus induced osteomyelitis. Mean age was 38±4,2(26 to 53)). After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal pellets loaded with different antibiotics depending from the antibiotic sensitivity test. Endpoints were the absence of clinical manifestation of infection or disease recurrence, no need for further surgery. Results. In vitro showed after 24 hrs inhibition zone was 4,2 х 4,9 cm, after 72 hrs the inhibition zone was increased till 7,6 х 8,4 cm. During the subsequent time, there were no changes. Results of the clinical study evidenced no signs of infection in 18 patients (86% (CI 69,8;100)) (p<0,05) at the follow up, while 3 (14%(CI 0;30,2)) (p<0,05) subjects showed infection recurrence at 6 months from operation and 2 of them needed further surgical procedures. Conclusion. PerOssal as an antibiotic carrier stabilizes the action of the antibiotic. This antibiotic carrier system allows to choose an antibiotic individually for each patient according to the antibiotic sensitivity test and can be successfully used in clinical cases of osteomyelitis

A multimodality approach is needed for management of infected joint replacement prostheses and infected skeletal metalwork. We present our results in six patients managed surgically with standard techniques, with the addition of a local antibiotic delivery system using absorbable Calcium Sulphate beads. A retrospective study was undertaken of 6 patients with established musculoskeletal infection in relation to existing metalwork. Two patients had infection in the hip replacement prosthesis, three had infected prosthetic knee joints and one had infection in a femoral locking plate. All were treated with extensive debridement, revision / retention of implants, parenteral antibiotics and local antibiotics. Patients were followed up in clinic for resolution of inflammatory markers and subsidence of signs of infection. Control of infection was achieved in five patients at average 19 months followup. One patient had persistent infection and has undergone further surgery. In this preliminary study, we found local antibiotic delivery using absorbable calcium sulphate beads to be an effective adjuvant to standard debridement, parenteral antibiotics and revision of implants

Aim. A prospective study to report the results of using gentamycin-collagen in the surgical treatment of osteomyelitis. Materials and Methods. After complete radiological and laboratory studies, empirical systemic Imipenem antibiotic was started pre-operatively followed by radical operation and implantation of Collatamp-EG®. Bone defects were treated with iliac or composite ceramic bone graft. Primary or secondary soft tissue reconstructive procedures were used. Closed gravitational suction drainage was used. Parental systemic antibiotics were continued for 2–3 weeks according to culture sensitivity results followed by oral therapy for another 4 weeks. Cattaneo et al scoring system was used to evaluate the final bony and functional results. Results. The mean number of Collatamp-EG® sponges implanted per patient were 3.6 and the mean follow-up period was 3.8 years. 85.7% of patients had showed positive cultures and staphylococcus aureus was the commonest cultured organism. The following complications were reported; pathological fracture (1), malnuion (2), nonunion (1). According to Cattaneo et al scoring system, bone healing was achieved in 94.4% of patients; bone infection control without relapse was achieved in 100% of patients. 89.2% of patients had complete functional recovery. Conclusions. Local antibiotic delivery system seems to be a useful and safe component in the armamentarium of the orthopedic surgeon dealing with bone infection by maximizing the local concentration while minimizing their systemic toxicity. Collatamp-EG® help bone and soft tissue repair without the need to remove it

Evaluation of the surgical approach and treatment outcomes in patients with chronic osteomyelitis of the tibia classified as anatomic type 3 and 4, physiologic class B (Cierny-Mader). Analysis of surgical treatment of 68 patients (average age of 45.6 years) with chronic osteomyelitis of the tibia covered the period from June 1, 2013 till January 1, 2015. There were 49 males (72%). The first (I) group included 39 patients with type 3 chronic osteomyelitis of the tibia, the second (II) group – 29 patients with type 4 osteomyelitis. The follow-up was for 1–18 months. Duration of the surgery, intraoperative blood loss, causes of osteomyelitis and the frequency of infection recurrence were evaluated. In the group I, 33.3% of patients underwent debridement of the infected site and replacement of the bone defect with an antibiotic-laden cement spacer. In 28.2% of cases, a biodegradable antibiotic delivery system was used for the replacement. 23.1% of cases involved muscle flap coverage of the bone and tissue defect, while 15.4% – treatment with external fixation. In the group II, the proportion of cases treated with external fixation was 58.6%. It was higher than in group I (p<0.01). 27.6% of patients in this group had their defects replaced with an antibiotic-laden cement spacer, whereas 10.3% had muscle flap coverage. One patient had amputation of the tibia. Duration of the surgery and blood loss in group II was 2.4 and 1.7 times higher than in group I. The frequency of infection recurrence in both groups was comparable (about 13%). The average time of its manifestation was 20.8 days in group II and 41.6 days in group I. Infection recurrence after muscle flap coverage was not observed. S.aureus was the most common pathogen in both groups (50–60%). Microbial associations were isolated in 28.3 and 38% of cases in groups I and II, respectively. 33.3% of patients experienced infection caused by P.аeruginosa. Differences in the blood loss and duration of the surgery were due to the larger volume of the affected tissues in type 4 chronic osteomyelitis of the tibia. High frequency of infection recurrence was observed in patients with microbial associations and P.aeruginosa. The surgical treatment of choice for these patients might be muscle flap coverage. It is necessary to consider the type of a pathogen for systemic and local antimicrobial therapy

Two-stage revision procedure is the gold standard in management of periprosthetic infections. Cement spacers have long been used to preserve the space created during resection procedure and to release antiobiotics within the created dead space. However, the problems related to cement as an antibiotic carrier are well recognised (thermal necrosis, random porosity, unspecified antibiotic delivery rate). To present the concept of using PerOssal as a canal filling spacer and local antibiotic delivery system in two-stage revisions of hip and knee infected arthroplasty. 8 patients (6 females, 2 males) with infected arthroplasty (4 TKRs, 4 THRs) were managed with two-stage revision procedures during the years 2006–2008 (minimum FU: 12 months). Our protocol consisted of:. Preoperative determination of the causative organism. Radical debridement surgery and cement spacer with PerOssal implantation. Appropriate IV antibiotic therapy for 6 weeks, postoperative clinical evaluation and monitoring of inflammation markers. After a six-week antibiotic free interval and inflammation markers normalization second stage surgery took place: Medullary canal reaming, intraoperative cultures, thorough wound irrigation and prostheses implantation. Postoperative antibiotic therapy until culture results; IV antibiotic treatment for 6 more weeks if they were positive. FU evaluation at 3, 6, 12, and 24 months. We had 7 cases with eradication of infection, 2 with delayed wound closure, and 1 late recurrence of disease. We think that PerOssal can offer a very useful additional and genuine support in managing infected joint arthroplasties with so far good clinical results

To evaluate the medium term results of the Lautenbach procedures for the treatment of chronic osteomyelitis [COM] in long bones. Cohort of 17 patients (18 segments) prospectively treated. Mean age 37 years. High-energy trauma effecting 8 tibia (6 open) & 9 femora (5 open). Duration of COM was mean 12. 5 years (1–31 years). Discharging sinus present in all. Lautenbach procedure comprises intramedullary reaming/debridement to 13 mm and establishment of local antibiotic delivery system, cavity analysis for volume and culture. The end point is 3 clear culture results of the irrigate, improvement in blood indices and reduction of cavity volume. Mean treatment time 27 days (14–48). Mean hospital stay 38 days. Two needed revision of Lautenbach procedure and one local debridement for recurrence of infection. 7 non-unions needed further fixation. 2 needed Papineau grafting and 3 had further limb lengthening procedures. Mean follow-up is 3. 3 years. 4 patients have been discharged, 1 awaiting THR. This procedure permits precise control over the osteomyelitis cavity until objective assessment suggests that infection has been cleared and cavity obliterated

Purpose. Gustilo type III open fractures are associated with high infection rates in spite of instituting a standard of care (SOC) consisting of intravenous antibiotics, irrigation and debridement (I&D), and delayed wound closure. Locally-delivered antibiotic has been proven to assist in reducing infection in open fractures. The aims of this study are to determine the effectiveness and safety of a new implantable and biodegradable antibacterial product. 1. in preventing bacterial infections and initiating bone growth in open fractures. Methods. The osteoconductive antibacterial BonyPid. TM. used is a synthetic bone void filler (comprised of ≤1 mm β-tricalcium phosphate granules) coated by a thin layer (≤20 µm) of PolyPid nanotechnology formulation. −. Upon implantation, the coating releases doxycycline at a constant rate for a predetermined period of 30 days. One BonyPid. TM. vial of 10 grams contains 65 mg of formulated doxycycline. After approval, sixteen subjects with Gustilo type III open tibia fractures, were implanted with the BonyPid. TM. immediately on the first surgical intervention (I&D), followed by external fixation. Patients had periodic laboratory, bacteriology and radiology follow-up. Results. Six months results showed that no infection developed and only one BonyPid. TM. implantation was needed with no subsequent I&D, in the target tibia fracture. Immediate soft wound closure was done in 6/16 subjects following implantation. Out of 10 remaining subjects, 3 needed soleus muscle transfer-skin grafting and 7 required delayed primary closure; by skin grafting (5) or suturing (2). Early callus formation was seen at 8–12 weeks post-surgery, followed by bone healing seen from 16 weeks onwards. Safety of implantation was remarkable, with only one deep infection at a fibular open fracture without BonyPid. TM. implantation. One BonyPid. TM. -related adverse event caused delay in skin healing due to excessive granules in the superficial soft tissues. Conclusion. BonyPid. TM. is effective in reducing bone infection and promoting early callus formation, resulting in early bone healing. BonyPid. TM. is safe for immediate implantation into contaminated/infected severe open-bone fractures. Results support that one month release of doxycycline in a controlled manner provides an effective way for treating open fractures. This new local antibiotic delivery system is applicable in unmet medical situations associated with localised infections

Introduction: Two-stage revision procedure is the gold standard in management of periprosthetic joint infections. Cement spacers have long been used to preserve the space created during resection procedure and to release antiobiotics within the created dead space. However, the problems related to cement as an antibiotic carrier are well recognised (thermal necrosis, random porosity, unspecified antibiotic delivery rate). Purpose: To present the concept of using PerOssal as a canal filling spacer and local antibiotic delivery system in two-stage revisions of hip and knee infected arthroplasty. Material & Methods: 8 patients (6 females, 2 males) with infected arthroplasty (4 TKRs, 4 THRs) were managed with two-stage revision procedures during the years 2006–2008 (minimum FU: 12 months). Our protocol consisted of:. Preoperative determination of the causative organism its sensitivity to antibiotics. Radical debridement surgery and cement spacer with PerOssal implantation. Appropriate IV antibiotic therapy for 6 weeks and postoperative clinical evaluation and monitoring of inflammation markers. After a six-week antibiotic free interval and if inflammation markers had return to normal second stage surgery took place: Medullary canal reaming, intraoperative cultures, thorough wound irrigation with 10L NS and prosthesis implantation. Postoperative antibiotic therapy until culture results; IV antibiotic treatment for 6 more weeks if they were positive. FU evaluation at 3, 6, 12, and 24 months. Results: We had 7 cases with eradication of infection, 2 with delayed wound closure, and 1 late recurrence of disease. Conclusion: We think that PerOssal can offer a very useful additional and genuine support in managing infected joint arthroplasties with so far good clinical results with respect to infection control

Bacterial infection of bone may result in bone destruction which is difficult to cure due to poor accessibility to bone of systemically-administrated antibiotic and poor performance of currently available local antibacterial treatments. PolyPid Ltd developed a novel local drug delivery system based on self-assembly of pharmaceutically approved lipids and polymers that encapsulate doxycycline (Doxy). The formulation is self-assembled lipid matrix via the interaction of the lipids (cholesterol and synthetic phospholipids) and biocompatible - biodegradable polymer (poly-lactic-co-glycolic). The entrapped Doxy is located within the anhydrous environment and therefore fully protected from both enzymatic and long-term water-exposure-related degradation. The fine coating of the tri-calcium phosphate (TCP) bone filler by this Doxy-containing formulation (BonyPid™) is capable of releasing intact and active drug at zero-order kinetics for a predetermined period of up to 30 days. The coating of the TCP granules with the polymer-lipids-Doxy formula (BonyPid™) did not change the granules’ macroscopic shape, but altered its color from white to pale yellow, which resemble the color of the entrapped Doxy. The average sizes of the non-coated TCP granules and the coated granules BonyPid™ were similar, as determined by measuring the widest dimension of each granule (1135±241 µm and 1072±242 µm, respectively, P=0.16). The MIC for Doxy that was released from BonyPid™ at different time points was similar to the non-encapsulated Doxy, suggesting full bioavailability of the released drug. BonyPid™ formulation structure was characterised by different physical methods including wide angle X-ray analyses (WAXS), differential scanning calorimetric (DSC) and SEM. WAXS analyses of BonyPid™ samples show a strong signal in the range of 1.3–1.8 2θ°, suggesting that the polymer and lipid TCP coating is a highly organised nano-substructure. The principle lipid in BonyPid™ formulation is phosphatidylcholine, which constitutes more than 85% of the overall lipid mass. It was found that the length of the acyl chains (14, 16 and 18 carbons, respectively) can significantly alter the release rate of Doxy during the prolonged (30 days), zero-order release phase, but did not alter the release profile. The anti-infection activity of BonyPid™ was tested in the rabbit tibia model contaminated with 5×10. 5. S. aureus. Both acute and chronic infection models were tested. Only BonyPid™ treatment demonstrated a statistically significant reduced bone absorption over the infected group (P<0.04 for day 7, 14 and 21) and significantly lower bacterial bone concentration (p>0.05) on day 21 following the bone grafting and the bacterial inoculation. In addition it was found that BonyPid™ did not reduce the osteo-conductivity as compared to non-coated TCP bone-filler. The first-in-man study for the treatment of contaminated / infected severe open long-bone fractures of BonyPid™ completed its 6 months follow-up. The results demonstrated high safety profile and significant efficacy; early bone callus formation and 0% infections in the BonyPid™ target bone fracture. Conclusion. Results demonstrate that BonyPid™ nan-technology that allow one month release of doxycycline in a controlled manner provides a new way for treating open fractures. This new local antibiotic delivery system is applicable in other medical situations associated with localised infections

Introduction: Chronic hip arthroplasty infection is a difficult situation to solve. The use of uncemented stem is questionable, as no antibiotic loaded cement is used to fix the implant. Bone deficiencies are often enlarged by the chronic infection process and the multiple previous surgeries. We report our experience in two stage revisions with massive allograft and uncemented distal locked stem. Material and method: We have retrospectively reviewed 15 patients operated on from chronic hip arthroplasty infection and secondary large femoral defects. Two stages revision with a temporarily antibiotic loaded cement spacer and 6-weeks second look reconstruction were performed with massive proximal femoral allograft and a long distally locked stem. The uncemented stem was cemented into the allograft and remained uncemented in the recipient distal femur. Outcome was assessed regarding infection control, allograft complication and function according to the Merle d’Aubigné score. Results: Patients mean age was 62 years (SD 11). Patients were already operated from the same hip 5.9 +/− 2.3 times before the actual procedure. Isolated microorganisms were MRSE (7), staph Aureus (4), MRSA (1), VRE (1), enterococcus (2). Muscle flaps were performed in 2 cases and discuss for 2 more. Allograft length was 22 +/− 9 cm. Antibiotic treatment was maintained for 4.6 +/− 2.5 months (median 3 months). Mean follow-up was 29 months (SD 26; median 23). Clinical outcome based on Merle d’Aubigné score is 5.3 +/− 3 before treatment and 13.8 +/− 2.5 at the last visit. Complications were registered in 4 cases. Infection recurrence was observed in 3 cases (2,7,20 months) but the function was preserved in all cases. One of them needed a two stage procedure with a new allograft after 19 months due to acute staph Aureus infection. One allograft was broken after 80 months and need one stage revision. Discussion: While the treatment of these cases was particularly demanding as bone deficiencies and microorganisms antibiotic resistance were high, functional result obtained was good. When infection recurrence was observed, function remains preserved. The use of uncemented distal locked stem with a cemented massive allograft did not lead to mechanical or hardware problem and allow us to restore the bone stock and the gluteus tendons insertion. The use of a modular stem was very helpful in solving these complex situations. Massive allografts can be used in case of infection as antibiotic delivery system

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Aims

The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

Aims

High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder.

Objective

In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits.

Objectives

Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin.

Objectives

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.