Aim. Fungal orthopaedic infections most commonly affect people with complex surgical histories and existing comorbidities. Recurrence and re-infection rates are high, even with optimal surgical and systemic antifungal treatment. AmBisome liposomal amphotericin B has been suggested for local antifungal therapy, as an adjunctive treatment for fungal osteoarticular infections. Few case series have examined its clinical use when combined with polymethylmethacrylate cement PMMA), or with absorbable local antibiotic carriers. We aimed to evaluate the clinical use of local antifungal therapy with AmBisome liposomal amphotericin B (ABlaB), including tolerated doses, serious adverse events, and treatment outcomes. Method. A retrospective cohort of all patients treated with local antifungal therapy with ABlaB between January 2016 and January 2021 in a specialist orthopaedic hospital was identified using pharmacy records. Renal function, serious adverse events during treatment, surgical outcomes including spacer fracture and infection recurrence, were identified from electronic clinical records. The project was approved by the Institutional Review Board (clinical audit 6871). Results. 13 operations involving local antifungal therapy with ABlaB, in 12 patients, were identified. Eleven were infected with Candida species and one with Aspergillus. Mean follow-up was 22 months (range 4–46). Ten first stage arthroplasty revisions, 2 second stage arthroplasty revisions, and one debridement and removal of metalwork for fracture-related infection were performed. Locally implanted doses of ABlaB ranged from 100mg to 3600mg (50–400mg per 40g mix of PMMA). Six patients received ABlaB in absorbable antibiotic carriers containing calcium sulphate. This was noted to delay carrier setting. Patients were also given systemic antifungal therapy. No patients experienced serious adverse events related to toxicity from local antifungal therapy with ABlaB. There were no spacer fractures. Overall treatment success was 54% at final follow-up, although there were no recurrent fungal infections identified in patients experiencing treatment failure. Conclusions. Local antifungal therapy with liposomal amphotericin B, when combined with surgery and systemic therapy, appears to be a safe and well tolerated intervention in the management of complex fungal osteoarticular infections

Aim. Local antibiotics, delivered to the site of infection, achieve high tissue concentrations and are used as an adjunct to systemic therapy. Local gentamicin provides levels well above the minimum inhibitory concentration and may be sufficient on its own, however, the efficacy of single or combination local antibiotics has not been studied. This retrospective study evaluated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Method. We studied patients with microbiologically confirmed osteomyelitis and fracture-related infection, who had implantation of antibiotic carriers as part of their surgical management. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. Results. There were 266 patients who met the inclusion criteria. Nine patients died before the outcome endpoint at 12 months and five patients were lost to follow up so were excluded. 252 patients were included in the final analysis and were well matched with regard to demographics, BACH score and microbiology. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. There was no difference for reoperation, ongoing suppressive antibiotic use, or clinical suspicion of infection. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95%CI 0.59-4.04, p=0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95%CI 1.13-10.76, p=0.03; Low BMI OR 0.91: 95%CI 0.84-0.99, p-0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p=0.434). Aminoglycoside resistance (confirmed and presumed) occurred in 39/113 (34.5%) of the aminoglycoside only group and 36/139 (25.9%) of the combination group (p=0.137). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95%CI 0.05-3.01, p=0.37). Conclusions. Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of osteomyelitis and FRI. Laboratory measured resistance, using currently accepted breakpoints, may not be relevant in local therapy

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in. sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use

Aim. In trauma surgery, the development of biomaterial-associated infections (BAI) is one of the most common complications affecting trauma patients, requiring prolonged hospitalization and the intensive use of antibiotics. Following the attachment of bacteria on the surface of the biomaterial, the biofilm-forming bacteria could initiate a chronic implant-related infection. Despite the use of conventional local and systemic antibiotic therapies, persistent biofilms involve various resistance mechanisms that contribute to therapeutic failures. The development of in vivo chronic BAI models to optimize antibiofilm treatments is a major challenge. Indeed, the biofilm pathogenicity and the host response need to be finely regulated, and compatible with the animal lifestyle. Previously, a Galleria mellonella larvae model for the formation of an early-stage biofilm on the surface of a Kirschner (K)-wire was established. In the present study, two models of mature biofilm using clinical Staphylococcus aureus strains were assessed: one related to contaminated K-wires (in vitro biofilm maturation) and the second to hematogenous infections (in vivo biofilm maturation). Rifampicin was used as a standard drug for antibiofilm treatment. Method. In the first model, biofilms were formed following an incubation period (up to 7 days) in the CDC Biofilm Reactor (CBR, BioSurface Technologies). Then, after implantation of the pre-incubated K-wire in the larvae, rifampicin (80 mg/kg) was injected and the survival of the larvae was monitored. In the second model, biofilm formation was achieved after an incubation period (up to 7 days) inside the larvae and then, after removing the K-wires from the host, in vitro rifampicin susceptibility assays were performed (according to EUCAST). Results. The first model indicate that in vitro biofilm maturation affects the bacterial pathogenicity in the host, depending on the S. aureus strain used. Furthermore, the more the biofilm is matured, the more the rifampicin treatment efficiency is compromised. The second model shows that, despite the fast in vivo biofilm formation in the host, the number of bacteria, either attached to the surface of the K-wire surface or in surrounding tissue of the larvae, was not increased over time. Conclusions. Altogether, these results allow the establishment of biofilm models using G. mellonella larvae in order to understand the impact of biofilm maturation on both the bacterial pathogenicity and the efficiency of antibiofilm treatments

Aim. Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction. Method. PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test. Results. VancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls. Conclusions. Treating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway. Acknowledgements. Funding comes from internal institutional grants

Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer

Aim. The duration of systemic antibiotic therapy following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, use high concentration targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy in the management of PJI of the hip using our two-stage protocol. Method. A retrospective review of our Institution's prospectively-collected database was performed to identify those patients who were planned to undergo a two-stage hip revision procedure for PJI. All patients had a confirmed diagnosis of PJI as per the major criteria of MSIS 2013, a minimum 5-years follow up and were assessed at the time of review using the MSIS working group outcome-reporting tool (2018). They were then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year). Results. 299 intended two-stage hip revisions in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage) met our inclusion criteria. 258 (86%) patients proceeded to 2. nd. stage surgery. Median follow up was 10.7 years. 91% success rate was observed for those patients who underwent reimplantation; dropping to 86% when including the patients who did not proceed to second stage surgery. The median duration of post-operative systemic antibiotics following first stage surgery was 5 days (IQR 5–9). No significant difference in outcome was observed in patients who received either; < / = 48 hours (86%; n=70) compared to > 48 hours antibiotics (86%; n=229; p=0.96) or </= 5 days of antibiotics (88%; n=202) compared to > 5 days antibiotics (82%; p=0.38). A significant majority had gram-positive (88%) infection with 30% being polymicrobial. Greater success rates were observed for gram-positive PJI (87%); than for gram-negative PJI (84%) and mixed Gram infection (72%; p=0.098). Conclusion. Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage hip surgery, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs

Aim. Implant-associated osteomyelitis is a devastating complication with poor outcomes following treatment, especially when caused by antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). A large animal model of a two-stage revision to treat MRSA implant-associated osteomyelitis has been developed to assess novel treatments. A bioresorbable, thermo-responsive hyaluronan hydrogel (THH) loaded with antibiotics has been developed and our aim was to investigate it´s in vivo efficacy as a local antibiotic carrier compared to the current standard of care i.e. antibiotic-loaded polymethylmethacrylate (PMMA) bone cement. Method. 12 female, 2 to 4 year old, Swiss Alpine Sheep were inoculated with MRSA at the time of intramedullary nail insertion in the tibia to develop chronic osteomyelitis. After 8 weeks sheep received a 2-stage revision protocol, with local and systemic antibiotics. Group 1 received the gold standard clinical treatment: systemic vancomycin (2 weeks) followed by rifampicin plus trimethoprim/sulfamethoxazole (4 weeks), and local gentamicin/vancomycin via PMMA. Group 2 received local gentamicin/vancomycin delivered via THH at both revision surgeries and identical systemic therapy to group 1. Sheep were euthanized 2 weeks following completion of antibiotic therapy. At euthanasia, soft tissue, bone, and sonicate fluid from the hardware was collected for quantitative bacteriology. Results. Sheep tolerated the surgeries and both local and systemic antibiotics well. Gold standard of care successfully treated 3/6 sheep with a total of 10/30 culture-positive samples. All 6 sheep receiving antibiotic-loaded THH were successfully treated with 0/30 culture-positive samples, p=0.0008 gold-standard vs. hydrogel (Fisher's Exact). Conclusions. The clinical gold standard treatment was successful in 50% of sheep, consistent with outcomes reported in the literature treating MRSA infection. The antibiotic-loaded THH clearly outperformed the gold standard in this model. Superior efficacy of the THH is likely due to 1) the ability to administer local antibiotics at the both revision surgies due to the bioresorbable nature of the hydrogel, and 2) complete antibiotic release compared to bone cement, which is known to retain antibiotics. Our results highlight the potential of local delivered, biodegradable systems for antibiotics for eradicating implant-related infection caused by antibiotic-resistant pathogens. Acknowledgement. Funding provided by AO Trauma

Aim. The treatment of chronic orthopedic device-related infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. In a two-stage exchange procedure, the treatment protocol includes device removal and placement of an antibiotic-loaded bone cement spacer to achieve high local antibiotic concentrations. At the second stage, further surgery is required to remove the spacer and replace it with the definitive device. We have recently developed a thermo-responsive hyaluronan hydrogel (THH) that may be loaded with antibiotics and used as delivery system. Since the material is bio-resorbable, it does not require surgical removal and may therefore be suitable for use as treatment strategy in a single-stage exchange. This aim of this study was to evaluate gentamicin sulphate (Genta)-loaded THH (THH-Genta) for treating a chronic Staphylococcus aureus ODRI in sheep using a single-stage procedure. Methods. Twelve Swiss-alpine sheep received an IM tibia nail and an inoculation of a gentamicin-sensitive clinical strain of Staphylococcus aureus. After letting a chronic infection develop for 8 weeks, a revision procedure was performed: the implant was removed, the IM canal debrided and biopsies were taken for culture. The IM canal was then filled with 25ml THH-Genta (1% Genta) or left empty (control group) prior to the implantation of a sterile nail. An ultrafiltration probe was placed within the IM cavity to collect extracellular fluid and determine local antibiotic levels for 10 days. Both groups received systemic amoxicillin and clavulanic acid for 2 weeks, followed by 2 weeks without treatment for antibiotic washout. At euthanasia, IM nail, bone marrow, bone and tissue samples were harvested for quantitative bacteriology. Results. All sheep were infected at revision surgery as confirmed by cultures of biopsies and sonication of the IM nail. Local Genta concentrations ranged on average from 830µg/ml postoperatively to below 5µg/ml after 8 days. At euthanasia, S. aureus was detected in 5/5 IM nails, 5/5 bone marrow samples, and 8/25 superficial soft tissue samples in the control group (one control sheep was excluded for having a superinfection). In the THH-Genta group, S. aureus was cultured from 0/6 IM nails, 1/6 bone marrow samples, and 1/30 superficial soft tissue samples. Conclusions. The THH showed a Genta release pattern that started with high local concentrations and decreased to low concentrations within 10 days. Local Genta delivery by THH combined with systemic antibiotics significantly reduced infection rates whereas systemic therapy alone was unable to eradicate infection in any animal

Two stage exchange treatment of the infected TKA involves two separate surgical procedures separated by an interval of several weeks of pathogen specific antibiotic therapy. The first stage involves removal of all of the infected arthroplasty components and any cement or foreign material, followed by aggressive debridement of nonviable bone and soft tissues. This is followed by placement of an antibiotic-laden spacer which may be either static (molded solid PMMA block) or mobile (shaped blocks or implants that allow knee motion). With both static and mobile spacers high local doses of antibiotic are delivered from the cement in addition to systemic antibiotic therapy usually employing an IV for around 6 weeks post debridement. The choice between static and mobile spacers is dictated by surgeon preference, soft tissue status (i.e. need for adjunctive muscle flaps), and by the severity of bone loss present with static spacers more likely to be used for more major soft tissue or bone defect cases. Mobile spacers have the advantage of allowing interval motion of the knee which may improve final range of motion. Static spacers usually require adjunctive brace or cast immobilization to prevent migration and bone damage. The second stage is performed at around 6 to 8 weeks after completion of systemic antibiotic therapy and preferably after normalization (or improvement) in laboratory indicators such as ESR and CRP. Routine repeat aspiration of all knees before reimplantation is not usual, but selective aspiration for culture may be helpful if concern exists that infection may still be present due to systemic signs, wound appearance or abnormal laboratory parameters. The second stage procedure involves removal of the antibiotic-laden spacer, repeat complete debridement of the knee, and insertion of revision knee components. Frequently adjunctive stems, blocks, cones or sleeves are needed to achieve adequate implant fixation due to associated bone loss. Careful attention to soft tissue balancing is required at the time of reimplantation in order to optimise motion and function while also avoiding laxity or maltracking. Two stage exchange remains the gold standard in North America for the management of infected TKA. While this method is used by some surgeons for all chronically infected TKA patients, it is employed even by most one stage exchange devotees when the infecting organism is unknown, infection involves a highly resistant or difficult to manage pathogen (i.e. fungal), is associated with a sinus track or marginal soft tissues, or in many cases of immunocompromised patients or those with multiple comorbidities

Aim. Antibiotic loaded spacers are often used during a two-stage exchange for periprosthetic joint infections (PJI) both for its mechanical properties and as a means for local antibiotic delivery. The main goal of this study is to compare the rate of positive cultures during reimplantation with the use of different antibiotic loaded spacers: aminoglycoside only vs. combined glycopeptide/aminoglycoside vs. combined glycopeptide/carbapenem/aminoglycoside. Method. We retrospectively evaluated every two-stage exchange procedures for infected hip/knee arthroplasty between 2012–2018. Microbiological findings in the first and second stage were registered as well as the type of spacer and antibiotic(s) used. Cases in whom no cultures were obtained during reimplantation and cases without sufficient data on antibiotic(s) used in cement spacers were excluded. Results. Fifty-four cases were included (20THA and 34TKA), with an overall rate of positive cultures during reimplantation of 18.5% (10/54). The rate of positive cultures was statistically significant higher among spacers with monotherapy with aminoglycoside compared to spacers with combined antibiotic therapy- 35.7% (5/14) vs. 12.5% (5/40) respectively(p<0.05). Comparing those with combined glycopeptide/aminoglycoside (2/19) with triple glycopeptide/carbapenem/aminoglycoside therapy (3/21) there was no significant difference. Microorganisms present during the second stage were mostly staphylococci (coagulase-negative in four cases, S.aureus in three), Corynebacterium striatum, Enterococcus faecalis, C.albicans in one case each. In most cases (8/10), the isolated microorganism was the same as the first stage and was resistant to the antibiotic(s) used in the spacer in seven cases. Failure rate with the need for subsequent surgery was significantly higher at 60% (6/10) in cases with positive cultures at reimplantation compared to 4.5% (2/44) for those with negative cultures during reimplantation(p=0.0005). Conclusions. It has recently been suggested that adding a glycopeptide to the spacer may be advantageous when compared to spacers with aminoglycoside monotherapy, as it will produce significantly lower rates of positive cultures during reimplantation which have been shown to increase the risk of subsequent failure as is the case in our study. Local unavailability of obtaining powder aminoglycosides has driven us to manually add high doses of vancomycin and meropenem to commercially available low-dose gentamicin cement in many of our spacers and they seem to to perform just as well as commercially available vancomycin/gentamicin combination. Although many other variables not considered in this study may influence the rate of positive cultures during the second stage (quality of initial debridement, systemic antibiotic therapy, etc.), we believe these results portrait a sufficiently accurate picture of clinical results with the use of different spacers

Aims

It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs.

Aim. Propionibacterium acnes (PA) is an important cause of shoulder prosthetic joint infections (SPJIs) for which the optimal treatment has not yet been determined. Rifampicin and Levofloxacin both showed not benefit in recent experimental models of PA-SPJIs. We describe herein the experience of five different medical French centers in order to assess factors associated with patient's outcome with special emphasize on antibiotic regimens. Method. A multicentric retrospective study was performed, on consecutive patients with PA – related SPJIs diagnosed on the basis of at least 2 or more positive cultures of either per-operative or joint aspiration and clinical history compatible with a PJI according to the current guidelines. All patients had surgical management, followed by systemic antibiotic therapy. Remission was defined as an asymptomatic patient with functioning prosthesis at the last contact. Results. Fifty-nine patients of mean age 66.2 ± 10.5 years were included. Most patients were at least ASA 2 (66%), 8 (14%) diabetes mellitus, 3 (5%) had neoplasia. Fourteen patients (24%) had acute, 34 (58%) subacute, and 11 late infections (19%). The mean delay from symptoms of infection to surgery was 89 ± 141 days (1–660). Surgical management consisted in implant exchange in 40 (68%) patients. Antibiotic treatment included mainly clindamycin (49%), levofloxacin (44%) and rifampin (17%), with a mean duration of 52.3 ± 31.9 days. The mean follow-up duration was 540 days ± 488 (range 12 ™ 1925). Forty-five patients were in remission (76%) in this study, 8 patients had a relapsing infection (14%), 1 a recurrence (2%) and 5 a superinfection ™ i.e, due to a different pathogen − (8%). In monovariate analysis, rifampicin/levofloxacin treatment was significantly associated with failure (p=0.038). In multivariate analysis, levofloxacin use and implants retention were significantly related to failure (p=0.02 and p=0.003, respectively). Conclusions. Our results suggest that implant retention and levofloxacin use are two independents factors of failure in patients treated for PA – related SPJIs

Aim. The treatment of osteomyelitis often requires extensive surgical debridement and removal of all infected tissues and foreign bodies. Resulting bone loss can then eventually be managed with antibacterial bone substitutes, that may also serve as a regenerative scaffold. Aim of the present study is to report the clinical results of a continuous series of patients, treated at our centre with an antibacterial bioglass*. Method. From November 2010 to May 2016, a total of 106 patients, affected by osteomyelitis, were included in this prospective, single centre, observational study. Inclusion criteria were the presence of osteomyelitis with a contained bone defect or segmental defects < 10 mm, with adequate soft tissue coverage. All patients underwent a one-stage procedure, including surgical debridement and bone void filling with the bioactive glass*, with systemic antibiotic therapy and no local antibiotics. Clinical, radiographic and laboratory examinations were performed at 3, 6 and 12 months and yearly thereafter. Results. Two patients were lost to follow-up, hence a total of 104 patients (65 males, 39 females; mean age: 46 ± 17 years, min 6 – max 81) were available at an average follow-up of 38 ± 26 months (range: 12 – 68); forty-eight patients (46.1%) were classified as Type A, 48 (46.1%) as Type B and 8 (7.7%) as Type C hosts, according to McPherson classification. Tibia (N=61) and femur (N=33) were the most common involved bones. On average patients had undergone 2.1 ± 1.3 (min 0 – max 7) previous surgical operations, with a mean infection duration of 18.7 ± 16.6 months (min 2 – max 120). Infection recurrence was observed in 10 patients (9.6%), most often within one year from surgery (8/10). Negative prognostic factors included infection duration > 2 years, Gram negative or mixed flora or negative cultural examination, Type B or C hosts and soft tissue defect. No side effects or complications related to bioglass were noted. Conclusions. This is to our knowledge the longest and the largest single centre consecutive series of patients, affected by bone infections of the long bones, treated according to a one-stage procedure using bioactive glass. Our results confirm, on a larger population and at a longer follow-up, previous reports. Early treatment, pathogen identification and adequate management of soft tissues should be considered to further reduce infection recurrence rate. *BonAlive®

Aim. The optimal surgical approach for patients hospitalized for moderate to severe septic bursitis is not known, and there have been no randomized trials of a one-stage compared with a two-stage (i.e., bursectomy, followed by closure in a second procedure) approach. Thus, we performed a prospective, non-blinded, randomized study of adult patients hospitalized for an open bursectomy. Method. Patients were randomized 1:1 to a one-stage vs. a two-stage surgical approach. All patients received postsurgical oral antibiotic therapy for 7 days. These are the final results of the prospective study registered at ClinicalTrials (NCT01406652). Results. Among 164 enrolled patients, 130 had bursitis of the elbow and 34 of the patella. The surgical approach used was one-stage in 79 and two-stage in 85. The two groups were balanced with regards to sex, age, causative pathogens, levels of serum inflammatory markers, co-morbidities, and cause of bursitis. Overall, there were 22 treatment failures: 8/79 (10%) in the one-stage arm and 14/85 (16%) in the two-stage arm (Pearson-χ2-test; p=0.23). Recurrent infection was caused by the same pathogen a total of 7 patients (4%), and by a different pathogen in 5 episodes (3%). The incidence of infection recurrence was not significantly different between those in the one- vs. two-stage arms (6/79 vs. 8/85; χ2-test: p=0.68). In contrast, outcomes were better in the one- vs. two-stage arm for wound dehiscence (2/79[3%] vs. 10/85[12%]; p=0.02), median length of hospital stay (4.5 vs. 6 days), nurses’ workload (605 vs. 1055 points) and total costs (6,881 vs. 11,178 Swiss francs) (all p<0.01). Conclusions. For adult patients with moderate to severe septic bursitis requiring hospital admission, bursectomy with primary closure, together with 7 days of systemic antibiotic therapy, was safe, resource-saving and effective. Using a two-stage approach did not reduce the risk of infectious recurrence, and may be associated with a higher rate of wound dehiscence than the one-stage approach

Introduction. Perioperative dexamethasone has been shown to effectively reduce post-operative nausea and vomiting and aide in analgesia after total joint arthroplasty (TJA), however systemic glucocorticoid therapy is carries the theoretical risk of increased susceptibility to prosthetic joint infection (PJI), increased white blood cell (WBC) counts, and increased blood glucose levels. The purpose of this study is to determine the effect of dexamethasone on PJI, WBC count, and blood glucose levels in diabetic and non-diabetic patients undergoing TJA. Methods. A retrospective chart review of all patients receiving primary total joint (hip or knee) arthroplasty between January 1, 2013 and December 31, 2015 (n = 1818) was conducted. The patients were divided into two main cohorts: those receiving dexamethasone (n = 1426) and those not receiving dexamethasone (n = 392); these groups were further subdivided into diabetic (n = 428 dexamethasone; n = 129 no dexamethasone) and non-diabetic patients (n = 998 dexamethasone, n = 263 no dexamethasone). The primary outcome was PJI; secondary measures included in (WBC) count, glucose levels, and days to infection. Statistics were carried out using chi-squared or ANOVA tests. Results. Of the 1818 joints, 1.05% (19) developed PJI; there was no significant difference between the dexamethasone and no dexamethasone groups (p = 0.1023): 12 (0.84%) in the dexamethasone group and 7 (1.79%) in the no-dexamethasone group. Additionally there was no significant effect on the increase in WBC count (p = 0.1784) or on the increase in blood glucose (p = 0.3120). Further subdividing the patients, there was a significantly higher rate of infection in those who received dexamethasone with diabetes (2.1%) compared to those without diabetes (0.30%) (p = 0.0016). Further, diabetics who received dexamethasone had a significantly greater elevation in blood glucose (p < 0.0001) compared to non-diabetics, but no significant change in WBC count (p = 0.6993). Conclusion. Perioperative intravenous dexamethasone had no statistically significant effect on the overall rate of prosthetic joint infections in primary total hip or knee arthroplasty; however diabetic patients had a significantly higher rate of infection compared to non-diabetics when given dexamethasone. WBC counts were not affected overall by administration of dexamethasone, or with stratification into diabetics and non-diabetics. Glucose levels were not effected by administration of dexamethasone

Aim. To prevent infections after orthopaedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics and may provide the necessary local antibiotic levels for prophylaxis. To be efficient a prolonged release is required. In contrast to vancomycin with proven efficient prolonged release from Osteomycin, this has not been described for cefazolin. We developed a protocol to bind cefazolin to bone chips by means of a hydrogel composed of proteins naturally present in the human body. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analysed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Conclusions. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile seems desirable, with high initial levels to maximize anti-bacterial action and low levels for a limited time to stimulate osteogenesis. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Aim. Treatment principles of chronic osteomyelitis include debridement, clean sampling, excision of dead bone, stabilization, dead space management, soft tissue closure and systemic antibiotic therapy. Dead space management becomes very complicated, if the bone infection is caused by multi-resistant bacteria. The aim of this investigation was to evaluate the effect of a new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. in the treatment of chronic osteomyelitis (OM) caused by multi-resistant bacteria. Method. From June 2015 to November 2015, 7 patients (4 males, 3 females, average age 52.6y) were treated according to the above mentioned principles using the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. Infections were caused by methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant Staphylococcus epidermidis (MRSE) and polymicrobial, vancomycin-sensitive bacteria. We used a two-stage protocol with debridement, excision of bone and external stabilization in the first stage, followed by bone defect reconstruction. To fill the residual bone defects, in 3 patients the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. (10mL) was used on its own and in 4 patients combined with 18mL of an unloaded calcium sulfate / hydroxyapatite composite. **. Post-operative follow-up was evaluated clinically and by radiographs and CT scans at 6, 14 and 24 weeks. Results. In 6 of 7 patients rapid control of infection was achieved. Soft tissue reactions and prolonged white wound drainage (caused by calcium sulfate dissolution) was seen in 3 of 7 patients. In 6 of 7 patients recurrence of infection has not been observed so far. Radiographs showed different elution intervals of the radiocontrast agent (Iohexol), depending on anatomical location. Bone remodelling or replacement of the composite by new bone was not uniform in the patients and showed specific radiographic signs. In addition to the so-called „puddle sign“, we found septae, membranes, vacuoles and sometimes arc-like structures. Therefore, we suggest the name “arc-sign” for these formations. Conclusions. During the follow-up of the first 7 patients treated with the unloaded calcium sulfate / hydroxyapatite composite. **. in 6 of 7 cases no recurrence of infection was observed. This is very promising in the difficult situation of bone infections caused by multi-resistant bacteria. Follow-up radiographs and CT-scans showed specific patterns during the resorption of the composite and the formation of new bone, which have not been described in other bone graft substitutes so far. The bone defects are not completely filled yet, but the affected bones are clinically stable and patients can ambulate with full weight bearing

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

Osteoarticular infections in paediatric population are primarily hematogenous in origin, although cases secondary to penetrating trauma, surgery or contiguous site are also reported. Despite being rare, numerous studies report infection relapse rates around 5 %. Osteomyelitis complications in children include septic arthritis, osteonecrosis of the bone segment, impaired growth. 7 years old male patient presented with history of traffic injury in January 2004. He sustained closed diaphyseal fracture of the right femur initially treated by elastic osteosynthesis. Four years after traffic injury he was diagnosed at our Institution of chronic femoral Osteomyelitis with positive cultures for methicillin sensible Staphylococcus aureus, requiring multiple surgical debridements and systemic antibiotic therapy. Five years follow- up the patient developed valgus deformity of his right knee (mechanical axis 11° genu valgum) with limb length discrepancy of 15 mm, intermalleolar distance of 15 cm and bone edema in external compartment of the knee (MRI). At this time the patient did not present any recurrence of septic process with normalization of laboratory parameters (ESR and CRP) and clinically asymptomatic. In February 2014, at the end of growth, a distal femoral varus osteotomy was used to treat valgus knee malalignment. Medial closing wedge osteotomy was performed satisfactorily using Tomofix® Osteotomy System (DePuySynthes). 18 months follow- up after varus osteotomy the patient progressed satisfactorily without pain and a normal function of his right knee. Correction limb length discrepancy was achieved (5 mm) with a normal alignment of his right limb (mechanical axis 3° genu valgum). Although Osteomyelitis is not very frequent in children population, its treatment requires not only prolonged antibiotic therapy but also multiple surgical debridements. We recommend monitoring over a long period of time children affected with Osteomyelitis in order to prevent and treat correctly impaired growth