Treatment Of Chronic Bone Infections Research Articles

Dual drug delivery system of teicoplanin and phenamil based on pH-sensitive silk fibroin/sodium alginate hydrogel scaffold for treating chronic bone infection.

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10days. The eluted TEC maintained its antibacterial activity of >75% during 35days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

Does local implantation of gentamicin impair renal function in patients undergoing surgery for chronic bone infection?

<p><strong>Background: </strong>The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity. We aim to establish the risk of acute kidney injury (AKI) with local delivery in a ceramic carrier.</p><p><strong>Methods: </strong>163 patients with Cierny-Mader type 3 or 4 chronic osteomyelitis had a single-stage operation including filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. Mean gentamicin dosing was 191.3 mg (maximum 525 mg). Glomerular filtration rate (GFR) was calculated pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the chronic kidney disease (CKD) staging system, and AKI was assessed using the RIFLE criteria.</p><p><strong>Results: </strong>155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 had pre-existing renal disease. 70 patients (45.2%) had a temporary GFR drop post-operatively, with the greatest decrease occurring at a mean of 3.06 days following surgery. Twenty cases had a >10% decline in GFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. </p><p><strong>Conclusions: </strong>Renal function is not significantly affected by local implantation of gentamicin up to 525 mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy.</p><p><strong> </strong></p>

Use of contemporary biomaterials in chronic osteomyelitis treatment: Clinical lessons learned and literature review.

Chronic osteomyelitis has always been a therapeutic challenge for patient and surgeon due to the specific problems related with bone infection and bacterial biofilm eradication. Other than being the cause of infection or facilitating spread or persistence of infection, biomaterials are also becoming a tool in the treatment of infection. Certain novel biomaterials have unique and ideal properties that render them perfectly suited to combat infection and are therefore used more and more in the treatment of chronic bone infections. In case of infection treatment, there is still debate whether these properties should be focused on bone regeneration and/or their antimicrobial properties. These properties will be of even greater importance with the challenge of emerging antimicrobial resistance. This review highlights indications for use and specific material properties of some commonly used contemporary biomaterials for this indication as well as clinical experience and a literature overview.

A preliminary in vitro evaluation of the bioactive potential of cryogel scaffolds incorporated with Manuka honey for the treatment of chronic bone infections.

Previous studies have identified honey as an agent in bacterial inhibition and a mediator in lowering the pH at the wound site. Manuka honey (MH), indigenous to New Zealand, contains a Unique Manuka Factor that provides an additional antibacterial agent. While there are many potential benefits to incorporating MH into wounds, there is currently no ideal way to deliver the material to the site of injury. Cryogels are a type of scaffold that possess high porosity, mechanical stability, and a sponge-like consistency. This study uniquely incorporates varying amounts of MH into cryogel scaffolds, utilizing its properties in a sustained release fashion to assist in the overall healing process, while using the cryogel structure as a tissue template. All cryogels were evaluated to determine the effects of MH on porosity, swelling potential, mechanical durability, and cell compatibility. The release of MH was also quantified to evaluate bacterial clearance potential, and the scaffolds were mineralized to replicate native bone. It was determined that a 5% MH silk fibroin cryogel has the potential to inhibit bacterial growth while still maintaining adequate porosity, mechanical properties, and cell infiltration. Such a scaffold would have use in a number of applications, including bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1918-1933, 2018.

Treatment of Chronic Bone Infections Using the Collagen Based Haemostatic - Collatamp G

Treating chronic bone infection is challenging, requiring complete excision of the affected areas and antimicrobial therapy. Acquiring active concentrations of antibiotics is difficult, as well as filling up bone defects resulting from sequestrectomy, and very few methods of treatment address both issues simultaneously. The authors describe the clinical results after using Collatamp G, a collagen-based, antibiotic filled sponge with two actions: local delivery of high antibiotic doses without systemic side effects and enhancement of healing due to collagen, thus covering the bone defect without any further osteoplastic surgery. This paper thus identifies Collatamp G as a biomaterial able to solve the above mentioned problems in treating bone infections.Keywords: bone infections, collagen matrix, gentamicine, antibiotic delivery

Treatment of Chronic Bone Infection

The treatment of chronic osteomyelitis depends on the obstinate persistence of the offending micro-organism(s) and often results in long-term patient disability causing remarkable costs to the health care system. Difficulties of treating chronic osteomyelitis derive from biofilm-forming pathogens that resist the host immunologic defense and antimicrobial substances, and the need to treat osseous defects that result from the disease itself and eventual previous interventions. Established surgical techniques require multiple costly operations with extended periods of disablement and impairment of the patients, sometimes making the therapy worse than the disease. This article suggests a new operative approach to address biofilm-adapted antimicrobial therapy and reconstruction of bony defects using antibiotic-impregnated allograft bone. The technique is applicable to all stages of the Cierny-Mader classification, and detailed description of specifications for the respective procedure is provided. Local use of high antibiotic concentrations enable simultaneous internal fixation with osteosynthetic material and minimize the need for using systemic antibiotics. This treatment results in short hospital stays, reduced pain, and faster rehabilitation for patients, markedly reducing their burden and the costs of treatment. Recurrences may occur in 10% of cases, but may be treated by repeating the procedure.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

In vitro elution of vancomycin from biodegradable osteoconductive calcium phosphate–polycaprolactone composite beads for treatment of osteomyelitis

In this work, osteoconductive composite materials comprising a large volume fraction of a bioresorbable calcium phosphate ceramic (CaP) and a smaller amount of a polycaprolactone polymer (PCL) were studied as a degradable antibiotic carrier material for treatment of osteomyelitis. Beads loaded with 1 and 4wt.% vancomycin were prepared by admixing dissolved drug to an in situ synthesized dicalcium phosphate (DCP)-PCL or solution-mixed beta-tricalcium phosphate (βTCP)–PCL composite powder followed by high pressure consolidation of the blend at room temperature. Vancomycin release was measured in phosphate-buffered saline (PBS) at 37°C. All the beads gradually released the drug over the period of 4–11weeks, depending on the composite matrix homogeneity and porosity. Mathematical modeling using the Peppas equation showed that vancomycin elution was diffusion controlled. The stability of the antibiotic after high pressure application at room temperature was demonstrated by high-performance liquid chromatography–mass spectrometry (HPLC–MS) studies and MIC testing. The preservation of the structure and activity of vancomycin during the processing of composite beads and its sustained in vitro release profile suggest that high pressure consolidated CaP–PCL beads may be useful in the treatment of chronic bone infections as resorbable delivery vehicles of vancomycin and even of thermally unstable drug substances.

Therapeutic Aspects of Chronic Bone Infections and Management Challenges

This study aims to investigate various aspects of the treatment of chronic bone infections and the challenges in their management. The characterization of treatment of 73 patients with chronic bone infection was reported. The four management challenges including consultation delay, immune depression, extreme variety of clinical manifestations and non-use of CT or MRI were discussed in this study. We conducted a retrospective study at Aristide Le Dantec Hospital on 90 cases of chronic bone infection in 73 patients. The mean duration of symptoms before consultation was 36 months. More than half of the patients had a productive fistula at the first consultation. Sickle cell anemia was found in 6 patients. Multiple lesions were found in 10 patients; and long bones were affected in 90% of cases. The bacterial culture was positive in 93.15%. Staphylococcus aureus was the most isolated germ (68.35%). Seventy-two out of seventy-three patients were operated on. The procedure depended on anatomical and radiological lesions. Surgical treatment was associated with antibiotherapy which was firstly probabilistic and secondarily adapted to the results of bacterial culture. A favorable trend was found in 41 patients (56.16%). 32 cases of adverse effects were noted (43.83%), and 27 patients had recurrence after a favorable outcome. Several complications and sequelae were observed demonstrating the tenacity of these chronic infections.

Prevention of Surgical Site Infections in Bone and Joint Procedures

There is strong evidence that preoperative nasal S. aureus screening/decolonization will significantly reduce surgical site infections (SSIs) after joint prostheses implantation. There is some evidence that antibiotic-containing bone cement may lower SSI rates. Timely administration of perioperative systemic antibiotic prophylaxis is recommended for patients with implants who are undergoing dental treatment, urogenital surgery, upper endoscopy, sigmoidoscopy, or colonoscopy. Advanced skin disinfection by chlorhexidine-gluconate-impregnated cloths may be protective. There is evidence that clippers are favored for hair removal, rather than razors, but no significant advantage, as compared with other modes of hair removal, has been found. Antibiotic-coated intramedullary nails and antibiotic-impregnated bone grafts may be useful for the treatment of chronic bone infections. No recommendation can be made for wound dressing types. Laminar air flow systems do not seem to prevent SSI but may even cause harm, instead. There is a strong association between the annual number of surgical procedures and low SSI rates.

Safety and Effectiveness of Extracorporeal Shockwave Therapy: Results of a Rabbit Model of Chronic Osteomyelitis

Extracorporeal shockwave therapy (ESWT) is applied successfully in various orthopedic disorders. Since shockwaves have demonstrated significant bactericidal effectiveness in vitro, safety and effectiveness of ESWT in vivo were evaluated in a rabbit model of osteomyelitis. Chronic osteomyelitis was induced by injecting sodium morrhuate and Staphylococcus aureus into the proximal tibia of 12 New Zealand white rabbits. Four and five wk after the initial operation, soft focused ESWT was applied twice to the infected limbs. Clinical parameters and laboratory values were followed and blood samples were taken for culture before and 30 min after ESWT. Following sacrifice after 8 wk, lungs, spleen and kidneys were studied histologically for signs of sepsis and secondary infection. Tibial osteomyelitis was assessed clinically, and by radiologic, microbiologic and histologic procedures. Signs of bacterial spreading were not detectable after ESWT, neither in blood cultures nor in histologic analyses of representative organs. Temperature, body weight, C-reactive protein and white blood cell levels also remained unchanged after ESWT. Of particular interest, histologic scores of osteomyelitis were significantly decreased in the ESWT-group compared to the untreated control ( p = 0.019). However, S. aureus was still detectable in tissue samples of all animals. This is the first study investigating the effects of ESWT applied to infected target areas. ESWT of infected bone did neither induce bacterial spreading nor worsening of infection, and the results suggest the reported treatment protocol of ESWT to be beneficial in the treatment of chronic bone infections. (E-mail: gollwitzer@bone-and-joint.org)

Ulcère de Marjolin sur ostéite chronique: Diagnostic et résultats du traitement : 7 cas

Purpose of the study Malignant degeneration of chronic wound inflammation is a rare complication which almost always develops late. Unstable wounds and scar tissue related to chronic osteitis can degenerate after a long period of chronic inflammation. We report seven cases. Case reports Seven patients presented squamous-cell carcinoma of the skin which had developed on wounds related to deep bone infections. Three patients had chronic bone infections subsequent to posttraumatic osteitis, two after hematogenous osteomyelitis, one after osteitis which developed on a zone of radiation-induced necrosis, and one after a deep burn was complicated by osteitis. The skin lesions developed over a period of 43 years on average before the diagnosis of malignant degeneration was established. Most of the lesions presented as budding malodorous ulcers. The pathological diagnosis was spinocellular squamous-cell carcinoma in five cases and verrucous squamous-cell carcinoma in two. Conservative treatment with wide resection and flap cover was attempted in all seven patients. Results Treatment failed in four patients and three required amputation. One patient died two years after amputation with local recurrence and metastatic dissemination to the brain. Discussion The diagnosis of malignant degeneration requires pathological proof. Biopsy material should be obtained whenever there is a modification leading to the development of a fistula or the formation of a scar tissue over a focus of chronic osteitis. Prevention requires adapted treatment of chronic bone infections, avoiding directed wound healing which can lead to fragile unstable scar tissue subject to degeneration.

Fluorescent tetracycline labeling as an aid to debridement of necrotic bone in the treatment of chronic osteomyelitis.

The authors have found that several months of preoperative tetracycline administration will label living bone so that it fluoresces under a blacklight during surgery. This allows intraoperative differentiation of viable bone from necrotic sequestra, which require removal in the treatment of chronic bone infection.

The use of antibiotic-containing bead chains in the treatment of chronic bone infections

The implantation of gentamicin polymethylmethacrylate (PMMA) chains or minichains into infected osteomyelitic cavities is a well-established local antibiotic therapy supplementary to radical debridement. The gentamicin concentrations achieved at the site of infection are far above the MICs for most common pathogens in chronic osteomyelitis. Serum and urine concentrations are low, and nephrotoxic and ototoxic side-effects of this form of gentamicin application are not to be feared. Under local antibiotic therapy with gentamicin PMMA chains, primary wound healing as in aseptic surgery can be expected. Prolonged systemic antibiotic therapy is unnecessary. In a series of 405 cases, a success rate of 90.4% was obtained.

Use of quinolones for the treatment of osteomyelitis and septic arthritis.

The low minimal inhibitory concentrations and minimal bactericidal concentrations of the quinolones for most pathogenic gram-negative and many gram-positive organisms, the ease of their administration, and their good oral absorption make them good candidates for the treatment of chronic bone infections. Data presently available suggest that the quinolones are effective in the treatment of experimental osteomyelitis due to Pseudomonas aeruginosa, osteomyelitis due to other gram-negative organisms, and (when combined with rifampin) in the treatment of gram-positive osteomyelitides. Quinolones have also been shown to be effective in the treatment of experimental septic arthritis. These results were confirmed by clinical studies. Quinolones have been effective in the treatment of patients with gram-negative bacterial bone infections and have been as effective as conventional antistaphylococcal therapy in the treatment of osteomyelitis due to Staphylococcus aureus. Finally, it should be kept in mind that as yet quinolones have not been released for use as therapy for childhood infections.

USE OF INSTILLATION-SUCTION TECHNIQUE IN TREATMENT OF CHRONIC OSTEOMYELITIS

Willenegger's closed instillation-suction technique for the treatment of chronic bone infection is described in which infected bone is first exposed and all sequestra removed. Two drainage tubes are perforated, inserted and brought out through the skin between 3 and 4 cm from the wound. the perforated portions of the tubes are laid close to the infected area and the wound closed in layers. One tube is connected to a drip bottle containing antibiotic solution and the second to a continuous suction pump. Closed continuous steady flow instillation-suction is thus established. the results of 28 cases are presented out of which 26 cases showed clinical resolution of the infection.

The unsuccessful surgical management of post-traumatic chronic bone infection. What is the role of serum factors?

Investigations in patients with chronic post-traumatic bone infections show dysfunctions in non-specific host defense mechanisms. There is a decreased availability of complement-derived chemotactic serum factors vs. an increased alternate complement pathway activity. We suppose these dysfunctions are acquired during the development of an acute to a chronic infection. Further investigations will show if there are therapeutic measures which are able to improve host defense mechanisms. Then, the future treatment of chronic bone infections will hopefully be more successful.

Silver Anode Treatment of Chronic Osteomyelitis

Twenty-five patients with active, chronic osteomyelitis, resistant to conventional management, were treated with surgical debridement and daily application of electrically activated silver dressings. Sixteen (64%) cases resulted in closed, stable, pain-free wounds, with the remainder resulting in persistent drainage or amputation. Nine of 12 cases complicated by nonunion achieved union. In 13 patients an open-bone graft was performed and silver treatment continued: these tended to remain free of purulent drainage but fared no better than average in the long-term follow-up. The silver anode dressing seems to be an effective aid in the treatment of chronic bone infection when combined with adequate surgical debridement, thereby reducing the need for prolonged systemic antibiotics.

INSTILLATION-SUCTION TECHNIQUE IN CHRONIC OSTEOMYELITIS

1. A technique of closed instillation-suction for the treatment of chronic bone infection is described in which infected bone is first exposed and all necrotic material removed. Three perforated drainage tubes are inserted, and brought out through the skin some distance from the wound. The perforated parts of the tubes are laid close to the infected area and the wound closed in layers. Two of the tubes are connected to a drip bottle containing antibiotic solution, and the third to a continuous suction pump. Closed continuous instillation-suction is thus established, and has been maintained for up to six weeks. 2. The results in twelve cases are presented, two-thirds of which showed clinical resolution of the infection.