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Bone & Joint Research
Vol. 7, Issue 1 | Pages 46 - 57
1 Jan 2018
Zhou J Zhou XG Wang JW Zhou H Dong J

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. Methods. The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects. Results. The prepared gelatin/β-TCP scaffolds exhibited a homogeneously interconnected 3D porous structure. The G-TCP0 scaffold exhibited the longest duration of vancomycin release with a release duration of eight weeks. With the increase of β-TCP contents, the release duration of the β-TCP-containing composite scaffolds was decreased. The complete release of vancomycin from the G-TCP5 scaffold was achieved within three weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold showed the most efficacious performance in eliminating infections and repairing bone defects. Conclusions. The composite scaffolds could achieve local therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed the optimal porosity, interconnection and controlled release performance. Therefore, this scaffold could potentially be used in the treatment of chronic osteomyelitis defects. Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H. Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold. Bone Joint Res 2018;7:46–57. DOI: 10.1302/2046-3758.71.BJR-2017-0129.R2


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 7 | Pages 1063 - 1068
1 Sep 2001
Li XD Hu YY

We have developed a new drug-delivery system using reconstituted bone xenograft to treat chronic osteomyelitis. This material, which has the capabilities of osteoinduction and osteoconduction, was supplemented with up to 2000 times the minimum inhibitory concentration of gentamicin against Staphylococcus aureus to prepare a gentamicin-reconstituted bone xenograft-composite (G-RBX-C). In a rabbit model, we evaluated the release of gentamicin from this composite in vivo, its capability for induction of ectopic bone and the repair of segmental defects of the radius. There was a high level of concentration of antibiotics, which was sustained for at least ten days. In the study of induction of ectopic bone, there was abundant woven bone in the G-RBX-C group two weeks after operation. At 16 weeks after implantation of G-RBX-C the radial defects had been repaired, with the formation of lamellar bone and recanalisation of the marrow cavity. Our findings suggest that G-RBX-C may be useful in the treatment of chronic osteomyelitis


Bone & Joint Open
Vol. 4, Issue 7 | Pages 516 - 522
10 Jul 2023
Mereddy P Nallamilli SR Gowda VP Kasha S Godey SK Nallamilli RR GPRK R Meda VGR

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.

Methods

Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30).


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 3 | Pages 527 - 530
1 May 1998
Kawanabe K Okada Y Matsusue Y Iida H Nakamura T

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum.

We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good.

Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results.


The Journal of Bone & Joint Surgery British Volume
Vol. 63-B, Issue 2 | Pages 178 - 184
1 May 1981
Dekel S Francis M

Osteomyelitis was induced in the tibiae of rabbits by injecting a suspension of Staphylococcus aureus and sodium tetradecylsulphate, a sclerosing agent. These rabbits were then divided into two groups: one group remained untreated and the other was fed a diet containing sodium salicylate. Two and four weeks after induction of osteomyelitis the tibiae taken from untreated rabbits with osteomyelitis and incubated in vitro released significantly more prostaglandin E and F than the control uninjected or uninfected tibiae. Tibiae taken from rabbits treated with sodium salicylate showed minimal radiographic changes and a significantly decreased release of prostaglandin E and F compared to the untreated rabbits. Prostaglandins are known to be potent bone resorbing agents and the results of this study suggest that they may also be involved in the destruction of bone which is characteristic of osteomyelitis. The treatment of rabbits with osteomyelitis using anti-inflammatory drugs, which block synthesis of prostaglandins, in addition to antibiotics, may prevent the destruction of bone and possible sequestration thereby decreasing the risk of chronic disease


Bone & Joint Research
Vol. 3, Issue 7 | Pages 223 - 229
1 Jul 2014
Fleiter N Walter G Bösebeck H Vogt S Büchner H Hirschberger W Hoffmann R

Objective

A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation.

Method

A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months.


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 2 | Pages 246 - 252
1 Mar 1991
Wei G Kotoura Y Oka M Yamamuro T Wada R Hyon S Ikada Y

We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.


Aims. Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones. Methods. Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed. Results. Patient infection in both groups was eradicated after IMT surgery. As for reconstruction surgery, no substantial changes in the operative period (p = 0.852), intraoperative blood loss (p = 0.573), or length of hospital stay (p = 0.362) were found between the two groups. All patients were monitored for 12 to 60 months. The median time to bone healing was 4.0 months (interquartile range (IQR) 3.0 to 5.0; range 3 to 7) and 5.0 months (IQR 4.0 to 7.0; range 3 to 10) in Groups BMCA and BMAA, respectively. The time to heal in Group BMCA versus Group BMAA was substantially lower (p = 0.024). Conclusion. IMT with BMCA or BMAA may attain healing in large bone defects secondary to COM in children. The bone healing time was significantly shorter for BMCA, indicating that this could be considered as a new strategy for bone defect after COM treatment. Cite this article: Bone Joint Res 2021;10(1):31–40


The Journal of Bone & Joint Surgery British Volume
Vol. 67-B, Issue 3 | Pages 443 - 448
1 May 1985
Ross E Cole W

A protocol for the treatment of subacute haematogenous osteomyelitis has been used and evaluated in 71 children. A group of 26 children with a radiologically "aggressive" lesion had biopsy followed by antibiotics and immobilisation for six weeks. A group of 45 children with 48 cavities in the metaphysis or the epiphysis or both was further subdivided according to the presence or absence of clinical signs of pus at subperiosteal level or in a joint. Children with evidence of pus had operation followed by antibiotics and immobilisation while the remaining children were treated similarly but without operation. Intravenous cloxacillin or flucloxacillin and benzylpenicillin were given in hospital for 48 hours and oral antibiotics and immobilisation were then continued at home for six weeks. Staphylococcus aureus was the only pathogen cultured. In all, 91% were cured by a single course of treatment. Of the 48 metaphysial and epiphysial lesions, 77% were treated without operation; and of these, 87% were cured by a single course of treatment, this figure reaching 94% in children under 11 years old.


The Journal of Bone & Joint Surgery British Volume
Vol. 64-B, Issue 2 | Pages 218 - 223
1 Apr 1982
Cole W Dalziel R Leitl S

A protocol of treatment for acute haematogenous osteomyelitis has been evaluated in 75 children. Intravenous cloxacillin and benzylpenicillin were given in hospital until the child had improved after which oral antibodies and immobilisation were continued at home for a total of six weeks. Oral cloxacillin was used most frequently as Staphylococcus aureus was the major pathogen. Simple drainage of subperiosteal pus was carried out in the 17 children with clinical evidence of an abscess. Ninety-two per cent of the 55 children with acute osteomyelitis diagnosed early were cured by a single course of antibiotics without an operation and with less than one week in hospital. Only 25 per cent of the 12 children with late-diagnosed acute osteomyelitis were cured with a single course of antibiotics and an operation. A longer period in hospital, a prolonged course of antibiotics, and secondary operations were required to cure the other children. Seven (88 per cent) of the eight neonates and infants with acute osteomyelitis were cured with a single course of antibiotics and an operation with only one to two weeks spent in hospital. The remaining infant was cured with a further course of antibiotics. The overall cure rate with a single course of treatment was 83 per cent, and the remaining children were cured with further treatment. More children would be cured with a single course of antibiotics and immobilisation without the need for surgical intervention if treated was started within one or two days of the onset of the illness rather than after four to five days when the disease is more advanced with the formation of and abscess.


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 829 - 836
1 Jun 2014
Ferguson JY Dudareva M Riley ND Stubbs D Atkins BL McNally MA

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 5 | Pages 845 - 846
1 Nov 1987
Cole W


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 4 | Pages 593 - 596
1 Aug 1989
Yoshimura M Shimada T Matsuda M Hosokawa M Imura S

We treated 11 patients with chronic osteomyelitis of the tibia or the foot by local excision and transfer of a peroneal myocutaneous island flap. This flap, pedicled proximally or distally on the peroneal artery and veins, provides viable muscle to fill the dead space in bone and skin to close the defect. Ten patients reviewed more than three years after operation were all free of drainage with no clinical or radiographic evidence of recurrence.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims. This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods. We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results. In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months’ (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion. Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence. Cite this article: Bone Joint Res 2023;12(8):467–475


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1443 - 1450
1 Dec 2024
Down B Ferguson J Loizou C McNally M Ramsden A Stubbs D Kendal A

Aims. Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below-knee amputation, particularly in the presence of severe soft-tissue destruction. This study assesses the outcomes of single-stage orthoplastic surgical treatment of calcaneal osteomyelitis with large soft-tissue defects. Methods. A retrospective review was performed of all patients who underwent combined single-stage orthoplastic treatment of calcaneal osteomyelitis (01/2008 to 12/2022). Primary outcome measures were osteomyelitis recurrence and below-knee amputation (BKA). Secondary outcome measures included flap failure, operating time, complications, and length of stay. Results. A total of 30 patients (14 female, 16 male; mean age 53.7 years (95% CI 48.0 to 59.5)) underwent combined orthoplastic surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (IQR 11.75 to 49.25). Of these, 19 received a local flap and 11 received a free flap. The most common causes were fracture-related infection (n = 12; 40%) and ulceration (n = 10; 33%); 21 patients (70%) had already undergone at least one operation elsewhere. Osteomyelitis was eradicated in 23 patients (77%). There were seven patients who developed recurrent osteomyelitis (23%), all in the local flap group. One patient required a BKA. Univariate analysis revealed that local flap reconstruction (OR 13.5 (95% CI 0.7 to 269.7); p = 0.029) and peripheral vascular disease (OR 16.5 (95% CI 1.35 to 203.1); p = 0.008) were associated with increased risk of recurrence. Free flap reconstruction took significantly longer intraoperatively than local flaps (mean 481 minutes (408 to 554) vs mean 168 minutes (119 to 216); p < 0.001), but without significant differences in length of stay or frequency of outpatient appointments. Conclusion. In our study involving 30 patients, single-stage orthoplastic management was associated with 77% (n = 23) eradication of infection and only one amputation in this complex and comorbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. While good outcomes can be achieved, this treatment requires high levels of inpatient and outpatient care. Cite this article: Bone Joint J 2024;106-B(12):1443–1450


Bone & Joint Research
Vol. 5, Issue 3 | Pages 101 - 105
1 Mar 2016
Wang X Luo F Huang K Xie Z

Objectives. Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. Methods. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. Results. The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. Conclusion. The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used. Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101–105. DOI: 10.1302/2046-3758.53.2000487


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 151 - 157
1 Feb 2011
El-Husseiny M Patel S MacFarlane RJ Haddad FS

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity. This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis


Bone & Joint Research
Vol. 9, Issue 7 | Pages 394 - 401
1 Jul 2020
Blirup-Plum SA Bjarnsholt T Jensen HE Kragh KN Aalbæk B Gottlieb H Bue M Jensen LK

Aims. CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods. Osteomyelitis was induced in nine pigs by inoculation of 10. 4. colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results. All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion. The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 720 - 727
1 Jul 2024
Wu H Wang X Shen J Wei Z Wang S Xu T Luo F Xie Z

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

Methods

A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 815 - 820
1 Jul 2023
Mitchell PD Abraham A Carpenter C Henman PD Mavrotas J McCaul J Sanghrajka A Theologis T

Aims

The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems.

Methods

A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation.