Bone infection can recur months or years after initially successful treatment. It is difficult to review patients for many years to determine the true incidence of recurrence. This study determined the minimum follow-up period which gives a good indication of the recurrence rate after surgery for chronic osteomyelitis and infected non-union. We studied five cohorts of patients who had surgery for long bone infection, over a 10 year period. We investigated the efficacy of various antibiotic carriers (PMMA and Collagen; n=185, Calcium Sulphate; n=195, Calcium Sulphate/Hydroxyapatite; n=233) and management of infected non-unions (n=146). Patients were reviewed and Kaplan-Meier Survivorship curves were constructed to show the incidence and timing of recurrence. The microbiology of the initial infection and the recurrent culture was also compared.Aim
Method
We have reviewed the published classifications of long-bone osteomyelitis. This review demonstrated the limitations and poor recognition of existing classifications. We have designed a new system which includes four easily identifiable variables which are Bone involvement, Antimicrobial availability, Soft tissue coverage and Host status. This is called the B.A.C.H. classification system. In this study, we aim to retrospectively validate this classification in a cohort of osteomyelitis cases. We identified 100 patients who had received surgery for osteomyelitis between 2013–2015 in a single specialist centre. Each patient was classified retrospectively by two assessors who were not involved in the initial patient care. Osteomyelitis was confirmed in each patient by a validated composite protocol.Aims
Methods
Ilizarov described four methods of treating non-unions but gave little information on the specific indications for each technique. He claimed, ‘infection burns in the fire of regeneration’ and suggested distraction osteogenesis could effectively treat infected non-unions. This study investigated a treatment algorithm for described Ilizarov methods in managing infected tibial non-union, using non-union mobility and segmental defect size to govern treatment choice. Primary outcome measures were infection eradication, bone union and ASAMI bone and function scores. A consecutive series of 79 patients with confirmed, infected tibial non-union, were treated with one of four Ilizarov protocols, consisting of; monofocal distraction (26 cases), monofocal compression (19), bifocal compression/distraction (16) and bone transport (18). Median non-union duration was 10 months (range 2–168). All patients had undergone at least one previous operation (mean 2.2; range 1–5), 38 had associated limb deformity and 49 had non-viable non-unions. Twenty-six cases (33%) had a new simultaneous muscle flap reconstruction at the time of Ilizarov surgery and 25 had pre-existing flaps reused. Treatment algorithm based on assessment of bone gap and non-union stiffness, measured after resection of non-viable bone.Aims
Patients and Methods
Culture of multiple periprosthetic tissue samples is the current gold-standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through sonication fluid culture of explants. These current techniques can have relatively low sensitivity, with prior antimicrobial therapy or infection by fastidious organisms particularly influencing culture results. Metagenomic sequencing has demonstrated potential as a tool for diagnosis of bacterial, viral and parasitic infections directly from clinical samples, without the need for an initial culture step. We assessed whether metagenomic sequencing of DNA extracts from sonication fluid can provide a sensitive tool for diagnosis of PJI compared to sonication fluid culture. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopaedic device-related infections. Sonication fluids were filtered to remove whole human cells and tissue debris, then bacterial cells were mechanically lysed before DNA extraction. DNA was sequenced and sequencing reads were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples.Aim
Method
To investigate a treatment algorithm of various Ilizarov methods in managing infected tibial non-union. A consecutive series of 76 patients with infected tibial non-union were treated with one of four Ilizarov protocols, consisting of; monofocal distraction (25 cases), monofocal compression (18), bifocal compression/distraction (16) and bone transport (17). Median duration of non-union was 10.5 months (range 2–546 months). All patients underwent at least one previous operation, 36 had associated limb deformity and 49 had non-viable non-unions. Twenty-six cases had a new muscle flap at the time of Ilizarov surgery and 24 others had pre-existing flaps.Aims
Patients and Methods
In our Bone Infection Unit, epidural anaesthesia and sedation (EA+Sed) is the technique of choice for complex orthoplastic surgery involving lower limb free tissue transfer (LLFTT) (1) as it avoids complications of prolonged general anaesthesia (GA). Following our initial reports of successful use of audio-visual distraction (AVD) as an adjunct to regional anaesthesia we wished to evaluate the AVD effect on the patients’ experience during long duration, complex orthoplastic surgery for chronic osteomyelitis under EA+Sed. Our AVD equipment consists of a WiFi connected tablet and noise reducing head phones, providing access to downloaded music, films and the internet. Patients are also allowed to use their own equipment. All patients were fully informed about AVD and EA+Sed as a choice of anaesthesia. EA was established in the anaesthetic room and continued perioperatively. Sedation with propofol was titrated to the patients’ requirements to ensure comfort during surgery. All patients were followed up postoperatively with a structured questionnaire.Aim
Method
Eradication of infection in chronic osteomyelitis requires effective dead space management after debridement. Residual bacteria in biofilm may be resistant to normal levels of systemic antibiotic penetrating bone and will contribute to recurrence of osteomyelitis. This study evaluated a new antibiotic-loaded biocomposite in the eradication of chronic infection from bone defects. We report a prospective study of 100 patients with Cierny and Mader types III and IV chronic osteomyelitis, in 105 bones. Osteomyelitis followed open fracture or ORIF of closed fractures in 71%. Nine had concomitant septic arthritis. 80% had comorbidities (Cierny-Mader Class B hosts). Ten had infected non-unions. All patients were treated by a multidisciplinary team with a single-stage protocol including; debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with Cerament G™ and immediate primary skin closure. Stabilisation was required in 21 cases and 5 required joint fusion as part of the initial surgery. Plastic surgical skin closure was needed in 23 cases (18 free flaps). Patients were followed up for a minimum of one year (mean 19.5 months; 12–34).Aim
Patients and Method
Advocates of Debridement-Antibiotics-and-Implant-Retention (DAIR) in hip peri-prosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared to revision. However, no evidence supports this. This case-control study's aims were to compare outcome of DAIRs for infected 1° total hip arthroplasty (THA) with outcomes following 1° THA and 2-stage revisions of infected 1° THAs. We retrospectively reviewed all DAIRs, performed for confirmed infected 1° THR (DAIR-Group, n=80), in our unit between 1997–2013. Data recorded included patient demographics, medical history, type of surgery and organism identified. Outcome measures included complications, mortality, implant survivorship and functional outcome using the Oxford Hip Score (OHS). Outcome was compared with 2 control groups matched for gender and age; a cohort of 1° THA (1°-THA-Group, n=120) and a cohort of 2-stage revisions for infection (2-Stage-Revision-Group, n=66).Aim
Method
This study aimed to define the increased costs incurred by a return to theatre for cases requiring free tissue transfer for surgical treatment of chronic osteomyelitis. We hypothesised that there would be a significantly greater cost when patients required re-exploration of the free flap. We retrospectively analysed the costs of a consecutive series of sixty patient episodes treated at the Bone Infection Unit in Oxford from 2012 to 2015. Treatment involved excision of osteomyelitis with free tissue transfer for immediate soft tissue cover. We compared the costs of uncomplicated cases with those who returned to theatre and determined the profit/loss for the hospital from remuneration through the UK National Health Service Tariff Structure.Aim
Method
This study describes and correlates the radiographic and histologic changes which develop in a Gentamicin-eluting synthetic bone graft substitute 100 patients with COM were treated with a single stage procedure, including management of the dead space with insertion of a Gentamicin-eluting synthetic bone graft substitute Five patients had subsequent surgery, not related to recurrence of infection, which allowed biopsy of the implanted material. These biopsies were harvested between 12 days and 9 months after implantation. Tissue was fixed in formalin and stained with haematoxylin-eosin and immunohistochemically for bone matrix markers.Aim
Method
We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.Objectives
Materials and Methods
Bone and joint infections are not only common but their management can be technically complex. They carry significant healthcare costs and are a daunting experience for patients [1]. Frequently, multiple operations are required in order to treat the infection. Each surgical intervention usually results in greater bone loss, worsening skin and soft tissue scarring and increasingly diverse and resistant micro- organisms [2]. Specialist bone infection units involving highly integrated orthopaedic and plastic surgery, as well as infection physicians, may improve patient outcomes [3–4]. However, it is difficult to determine the hierarchy of factors contributing to outcome of treatment. This problem is confounded by a lack of structured, prospective data collection in many units around the world. In 2014, we designed a modular database which allows collection of patients’ details, components of the disease, the treatment, microbiology, histology, clinical outcome and patient-reported outcome measures (PROMS). The registry was implemented in November 2014 and has already demonstrated its function as a Hospital-wide service evaluation tool. Over 200 patients have been referred to the unit and their baseline demographic information registered. Their progress through the bone infection unit patient pathway is prospectively monitored with use of the registry and data collection ongoing. We aim to present the preliminary clinical outcomes of these 200 patients including surgical procedures performed, key microbiology results, antibiotic treatment regimens and patient reported outcomes. Our goal is to demonstrate that a bone infection registry is an integral part of infection management clinical practice. It can be used for designing service provision, assist in allocating healthcare resources and expand the evidence base for specialist bone infection units in managing complex orthopaedic infections.
Collection of 4–5 independent peri-prosthetic tissue samples is recommended for microbiological diagnosis of prosthetic joint infections. Sonication of explanted prostheses has also been shown to increase microbiological yield in some centres. We compared sonication with standard tissue sampling for diagnosis of prosthetic joint and other orthopaedic device related infections. We used standard protocols for sample collection, tissue culture and sonication. Positive tissue culture was defined as isolation of a phenotypically indistinguishable organism from ≥2 samples; and positive sonication culture as isolation of an organism at ≥50 cfu/ml. We compared the diagnostic performance of each method against an established clinical definition of infection (Trampuz 2011), and against a composite clinical and microbiological definition of infection based on international consensus (Gehrke & Parvizi 2013). 350 specimens were received for sonication, including joint prostheses (160), exchangeable components (76), other orthopaedic hardware and cement (104), and bone (10). A median of 5 peri-prosthetic tissue samples were received from each procedure (IQR 4–5). Tissue culture was more sensitive than sonication for diagnosis of prosthetic joint and orthopaedic device related infection using both the clinical definition (66% versus 57%, McNemar's Χ2 test p=0.016) and the composite definition of infection (87% vs 66%, p<0.001). The combination of tissue culture and sonication provided optimum sensitivity: 73% (95% confidence interval 65–79%) against the clinical definition and 92% (86–96%) against the composite definition. Results were similar when analysis was confined to joint prostheses and exchangeable components; other orthopaedic hardware; and patients who had received antibiotics within 14 days prior to surgery. Tissue sampling appears to have higher sensitivity than sonication for diagnosis of prosthetic joint and orthopaedic device infection at our centre. This may reflect rigorous collection of multiple peri-prosthetic tissue samples. A combination of methods may offer optimal sensitivity, reflecting the anatomical and biological spectrum of prosthetic joint and other device related infections.
Debridement, antibiotics and implant retention (DAIR) is a surgical option in the treatment of prosthetic joint infection (PJI). It is thought to be most appropriate in the treatment of early (≤6 weeks post-op) PJI. Most studies to-date reporting on DAIRs in hip PJI have been underpowered by reporting on small cohorts (n= <45), or report on registry data with associated biases and limitations. In our, tertiary referral, bone infection unit we consider DAIR to be a suitable option in all cases of PJI with a soundly fixed prosthesis, with early or late presentation, especially in patients who are too elderly or infirm to undergo major surgery. Aim: To define the 10-year outcome following DAIR in hip PJI and identify factors that influence it. We retrospectively reviewed all DAIRs performed in our unit between 1997 and 2013 for hip PJI. Only infected cases confirmed by histological and microbiological criteria were included. Data recorded included patient demographics and medical history, type of surgery performed (DAIR or DAIR + exchange of modular components), organism identified and type/duration of antibiotic treatment. Outcome measures included complications, mortality rate, implant survivorship and functional outcome. 121 DAIRs were identified with mean age of 71 years (range: 33–97). 67% followed an index procedure of 1° arthroplasty. 53% included exchange of modular components. 60% of DAIRs were for early onset PJI. Isolated staphylococcus was present in 50% of cases and 25% had polymicrobial infection. At follow-up (mean:7 years, range: 0.3 – 18), 83 patients were alive; 5- and 10- year mortality rates were 15% and 35% respectively. 45% had a complication (persistence of infection: 27%, dislocation: 10%) and 40% required further surgery. Twenty hips have been revised to-date (17%). Performing a DAIR and not exchanging the modular components was associated with an almost 3× risk (risk ratio: 2.9) of subsequent implant failure (p=0.04). 10-yr implant survivorship was 80% (95%CI: 70 – 90%). Improved 10-year implant survivorship was associated with DAIR performed for early PJI (85% Vs 68%, p=0.04). Functional outcome will be discussed. DAIR is a particularly valuable option in the treatment of hip PJI, especially in the early post-operative period. Whenever possible, exchange of modular implants should be undertaken, however DAIRs are associated with increased morbidity even in early PJI. Factors that predict success of DAIR in late PJI need to be identified.
To compare the costs of treatment and income received for treating patients with tibial osteomyelitis, comparing limb salvage with amputation. We derived direct hospital costs of care for ten consecutive patients treated with limb salvage procedures and five consecutive patients who underwent amputation, for tibial osteomyelitis. We recorded all factors which affect the cost of treatment. Financial data from the Patient-Level Information and Costing System (PLICS) allowed calculation of hospital costs and income received from payment under the UK National Tariff. Hospital payment is based on primary diagnosis, operation code, length of stay, patient co-morbidities and supplements for custom implants or external fixators. Our primary outcome measure was net income/loss for each in-patient episode. The mean age of patients undergoing limb salvage was 55 years (range 34–83 years) whereas for amputation this was 61 years (range 51–83 years). Both groups were similar in Cierny and Mader Staging, requirement for soft-tissue reconstruction, anaesthetic technique, diagnostics, drug administration and antibiotic therapy. In the limb salvage group, there were two infected non-unions requiring Ilizarov method and five free flaps. Mean hospital stay was 15 days (10–27). Mean direct cost of care was €16,718 and mean income was €9,105, resulting in an average net loss of €7,613 per patient. Patients undergoing segmental resection with Ilizarov bifocal reconstruction and those with the longest length of stay generated the greatest net loss. In the amputation group, there were 3 above knee and 2 below knee amputations for failed previous treatment of osteomyelitis or infected non-union. Mean hospital stay was 13 days (8–17). Mean direct cost of care was €18,441 and mean income was €15,707, resulting in an average net loss of €2,734 per patient. Length of stay was directly proportional to net loss. The UK National Tariff structure does not provide sufficient funding for treatment of osteomyelitis of the tibia by either reconstruction or amputation. Average income for a patient admitted for limb salvage is €6,602 less than that for amputation even though the surgery is frequently more technically demanding (often requiring complex bone reconstruction and free tissue transfer) and the length of hospital stay is longer. Although both are significantly loss-making, the net loss for limb salvage is more than double that for amputation. This makes treatment of tibial osteomyelitis in the UK National Health Service unsustainable in the long term.
To evaluate the clinical outcome of three different local antibiotic delivery materials, used as bone defect fillers after excision of chronic osteomyelitis. We reviewed all patients receiving Collagen Fleece with Gentamicin (Septocoll E)(n=74), Calcium Sulphate with Tobramycin pellets (Osteoset T)(n=166) or Calcium Sulphate/Hydroxyapatite biocomposite with Gentamicin (Cerament G)(n=73) for dead space filling after resection of C-M Stage III and IV chronic osteomyelitis. Data was collected on patient comorbidities, operation details, microbiology, postop complications and need for plastic surgery or external fixation. All operations were performed by two surgeons. All patients had similar systemic antibiotic therapy and rehabilitation. Primary outcomes were recurrence rate, fracture rate and wound leakage rate. All three groups had very similar mean age and range, microbiological cultures, need for free muscle flaps or local flaps, proportion of femur, tibia and upper limb bones and use of external fixation. There were small differences in the proportion of C-M Class B hosts and anatomic Type IV cases, between the groups. All patients were followed up for at least one year. Mean follow-up was 1.75 years for Septocoll E, 1.96 years for Osteoset T and 1.78 years for Cerament G. After surgery, there were fewer prolonged wound leaks with Cerament G (leakage persisting for more than 2 weeks). Fracture rates and infection recurrence were twice as common with Osteoset T compared with Cerament G at between one and two years after operation (see Table). The use of a biocomposite material delivering local aminoglycoside was associated with lower recurrence rates and few wound problems, compared with collagen or calcium sulphate alone. This may reflect the higher levels of antibiotic in the defect and controlled release profile. The improved recurrence rate was despite a higher percentage of compromised Class B hosts.
Treatment of open fractures is complex and controversial. The purpose of the present study is to add evidence to the management of open tibial fractures, where tissue loss necessitates cover with a free flap. We identified factors that increase the risk of complications. We questioned whether early flap coverage improved the clinical outcome and whether we could improve our antibiotic treatment of open fractures. From 2002 to 2013 we treated 56 patients with an open tibial fracture covered with a free flap. We reviewed patient records and databases for type of trauma, smoking, time to tissue cover, infection, amputations, flap loss and union of fracture. We identified factors thatincrease the risk of complications. We analyzed the organisms cultured from open fractures to propose the optimal antibiotic prophylaxis. Follow-up was minimum one year. Primary outcome was infection, bacterial sensitivity pattern, amputation, flap failure and union of the fracture. When soft tissue cover was delayed beyond 7 days, infection rate increased from 27% to 60% (p<0.04). High-energy trauma patients had a higher risk of amputation, infection, flap failure and non-union. Smokers had a higher risk of non-union and flap failure. The bacteria found were often resistant to Cefuroxime, aminoglycosides or amoxicillin, but sensitive to Vancomycin or Meropenem. Flap cover within one week is essential to avoid infection. High-energy trauma and smoking are important predictors of complications. We suggest antibiotic prophylaxis with Vancomycin and Meropenem until the wound is covered in these complex injuries. The authors wish to thank Christian E Forrestal for secretarial assistance, spreadsheets and figures, MD Maria Petersen for academic feedback and typography. Table: Culture results. Depicts the organisms isolated from the wounds, their number N and the number of bacteria that were fully susceptible to antibiotics according to the culture results in falling order on day 2–30 from the trauma. Most organisms were resistant to Cefuroxime. A blank space denotes that the organism was not tested against this antibiotic. A “0” denotes that the organism was not fully sensitive to the antibiotic.
Open tibial fractures have a high infection risk making treatment difficult and expensive. Delayed skin closure (beyond 7 days) has been shown to increase the infection rate in several studies (1). We aim to calculate the cost of infection as a complication of open tibial fractures and to determine the effect of delayed skin closure on this cost. We retrospectively reviewed all records of patients treated with a free flap in our institution for an open tibial fracture from 2002 to 2013. We calculated direct costs of treatment by the DRG-values (2014 figures), based on length of stay (LOS), diagnosis, orthopaedic and plastic surgical procedures and the corresponding reimbursement. The primary goal was to establish the extra cost incurred by an infection, compared to treating an uninfected open tibial fracture. The cost efficiency saving of early soft tissue cover was also investigated. We analysed 45 injuries in 44 patients. All patients were treated with debridement, stabilization, prophylactic antibiotics and free flap cover. Infection increased the mean total LOS in hospital from 28.0 to 63.8 days. The presence of an infection increased the cost of treatment from a mean of €49.301 for uninfected fractures compared to a mean of €67.958 for infected fractures. Achieving skin cover within 7 days of injury decreased the infection rate from 60% to 27% (total series rate 48%). The provision of early soft tissue cover (before 7 days) for all patients would have saved an average of €18.658 per patient. The development of an infection after a severe open tibial fracture greatly increases the cost of treatment. Early soft tissue cover is one aspect of care which has been shown to improve clinical outcomes. This study confirms that it will also reduce the cost of treating these complex fractures – underscoring the need for rapid referral and an ortho-plastic setup to handle them. We have only calculated the direct costs of treatment. Infected fractures will also consume extra costs in rehabilitation and absenteeism from later infection recurrence and non-union. Therefore, our estimate of the potential saving is likely to be conservative.
Squamous Cell Carcinoma (SCC) is a rare complication of chronic osteomyelitis (OM), arising in a sinus tract (Marjolin's Ulcer). We routinely send samples for histological analysis for all longstanding sinus tracts in patients with chronic osteomyelitis. We reviewed the clinical features and outcomes of patients with SCC arising from chronic osteomyellitis. A retrospective study was performed of patients with osteomyelitis between January 2004 and December 2014 in a single tertiary referral centre. Clinical notes, microbiology and histo-pathological records were reviewed for patients who had squamous cell carcinoma associated with OM. We treated 9 patients with chronic osteomyelitis related squamous cell carcinoma. The mean age at time of diagnosis was 51 years (range 41–81 years) with 4 females and 5 males. The mean duration of osteomyelitis was 16.5 years (3–30 years) before diagnosis of SCC. SCC arose in osteomyelitis of the ischium in 5 patients, sacrum in 1 patient, femur in 1 patient and tibia in 2 patients. Osteomyelitis was due to pressure ulceration in 7 patients and post-traumatic infection in 2 patients. The histology showed well differentiated SCC in 4 cases and moderately differentiated SCC in 2 cases with invasion. Two patients had SCC with involvement of bone. One patient had metastatic SCC to bowel. All patients had polymicrobial or Gram-negative cultures from microbiology samples. Four patients (57%) in our series died as result of their cancer despite wide resection. The mean survival after diagnosis of SCC was 1.3 years and mean age at time of death was 44.7 years. Two of these patients had ischial disease and were treated with hip disarticulation, hemi-pelvectomy and iliac node clearance. Five patients remain disease free at a mean of 3.4 years (range 0.1 – 7yrs) after excision surgery. One patient in this group underwent a through-hip amputation, one underwent an above knee amputation and one underwent excision of ischium and surrounding sinuses. Of note, all these patients had clear staging scans at time of diagnosis. This case series demonstrates the consequences of an uncommon complication of osteomyelitis. In our series only 3 patients underwent biopsy for suspected SCC due to clinical appearances. The other cases were all identified incidentally after routine histological sampling, demonstrating the importance of this practice.
Chronic osteomyelitis is a challenging clinical problem. Aggressive debridement, bony fixation, obliteration of dead space and vascularised soft tissue coverage with appropriate antimicrobial therapy are essential to successful management of this condition. The gracilis muscle flap is the workhorse flap in our unit for reconstruction of limb osteomyelitis. We describe the experience and use of this flap in our unit over a 3 year period. Clinical records were reviewed from a prospectively-maintained Oxford Free Flap Database and patient notes. All patients who received a free gracilis flap reconstruction as part of the treatment of osteomyelitis between 2011 and 2014 were included in the study. 40 patients received free gracilis flaps; 38/40 for lower limb and 2/40 for upper limb osteomyelitis. Two were myocutaneous flaps, and the remainder were muscle only. The return to theatre rate was 12.5% with a total flap loss rate of 5%. Other flap-specific complications include partial flap loss (2.5%), flap site haematoma (2.5%), donor site haematoma (2.5%) and seroma (2.5%). General complications included pulmonary embolism (2.5%) and death from sepsis (2.5%). All but 2 patients were treated successfully and remain disease free following their initial surgery, with a mean follow up of 12.4 months (range 1–23 months). We have found that the free gracilis muscle flap is effective in the successful treatment of osteomyelitis, with a low complication rate.