Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Introduction. The treatment of chronic osteomyelitis involves a debridement of affected non-viable tissue and the use of antibiotics. Where surgery leaves a cavity, dead space management is practised with antibiotic impregnated cement. These depots of local antibiotics are variable in elution properties and need removal. We review the use of bioabsorbable synthetic calcium sulphate as a carrier of gentamicin and as an adjunct in treating intramedullary osteomyelitis. Methods. A retrospective review of cases treated consecutively from 2006 to 2010 was undertaken. Variables recorded included aetiology, previous interventions, diagnostic criteria, radiological features, serology and microbiology. The Cierney-Mader system was used to classify. Treatment involved removal of implants (if any), intramedullary debridement and local resection (if needed), lavage and instillation of the gentamicin carrier, supplemented with systemic antibiotics. Follow-up involved a survival analysis to time to recurrence, clinical and functional assessment (AOFAS-Ankle/IOWA knee/Oxford Hip) and general health outcome (SF36). Results. There were 31 patients (22 male, 9 female). The mean age was 47 years (20–67). Twenty-five cases were post-surgery (6 open fractures) and 6 were haematogenous in origin. The median duration of osteomyelitis was 1.6yrs. The bones affected were 42% femur, 45% tibia, 3% radius and 10% humerus. 11 cases had diffuse as well as intramedullary involvement. 9 cases underwent segment resection and bone transport. We identified Staph. Aureus in 16 and Coag. Neg. Staph. in 6 cases. The median follow-up was 1.7 years (0.5–5.6). The median scores attained were: AOFAS-78, DASH-32, IOWA-71, Oxford-32. There were two recurrences. Discussion. Dead space management of intramedullary infections is difficult. We describe a method for delivery of local antibiotics and provide early evidence to its efficacy. The treatment success to date is 93%. Conclusion. Bioabsorbable carriers of antibiotics are efficacious adjuncts to surgical treatment of intramedullary osteomyelitis

Aim. Chronic osteomyelitis often requires surgical debridement and local antibiotic treatment. Disadvantages of PMMA carriers include low dose release and the requirement of surgical removal in the case of PMMA-beads. Synthetic nanocrystalline calcium phosphate (nCP) materials, which mimic the chemical structure of the mineral composition of bone, have been well accepted as bone grafting materials due to their consistent osteoconductivity, ease of use, and mechanical properties. Such a material which remodels into native bone is a much more attractive option. The aim of this study is to investigate the release of gentamicin from CaP in vitro and in vivo when implanted in a rabbit femoral condyle defect. Method. Three formulations of nCP were evaluated in this study: putty, paste and porous. Four cylindrical dowels were made for each group with gentamicin sulphate at a concentration of 20mg/cc of paste. Material was eluted in PBS at 37C and pH 7.0 and elutions were tested every day up to 30 days. Eighteen New Zealand white rabbits will undergo surgeries. Briefly, a drill defect will be created in the metaphyseal bone of the lateral femoral condyle. The formulations will be implanted in the created defect at time of surgery and the wound will be closed. Blood will be collected regularly and analysed for gentamicin titers. Animals will be sacrificed at 6wk, 12wk or 24wk. Explanted femurs will be fixed, sectioned and stained. Results. At 7 days the in vitro elution, showed a continued release of gentamicin. A large amount of gentamicin is released within the first day followed by a slow controlled release. The nCP putty shows the slowest release, followed by the paste and porous formulations respectively. There is a significant increase in the elution with an increase in porosity of the material. We expect to observe a similar trend in the rabbit study with an improved healing. At 6wk we expect the implant material to be still present at the site of implantation, which would remodel by 12wk and 24wk to significant levels due to active ossification. Conclusions. nCP materials, which undergo remodelling, can be used an effective carrier for gentamicin or other antibiotic agents. Because of its potentially prolonged release of high levels of antimicrobial agents, this system could maintain long-term antibacterial effectiveness locally

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

Currently, no clinical options are available to prevent infections on uncemented orthopedic implants. Therefore we investigated the efficacy of DAC-hydrogel (disposable antibacterial coating(1), Novagenit, Italy) as carrier for various agents to prevent infections in an in vivo implant-model. Titanium rods were implanted in the left tibiae in New Zealand White rabbits. Prior to implantation, the implant bed was contaminated with 10∧5 colony forming units S. aureus. In the experimental groups, the hydrogel was loaded prior to be coated on the rods with: 2%(w/v) vancomycin (Van2 group, N=6), 5%(w/v) vancomycin (Van5 group, N=6), 10%(w/v) bioactive glass (BonAlive, Finland) (BAG group, N=6), which is antibacterial(2) and osteoconductive(3), or 0.5%(w/v) N-acetyl cysteine (NAC group, N=6), which inhibits bacterial growth and decreases biofilm formation(4). In the control group, empty hydrogel was applied (Gel group, N=12). Blood values were measured weekly. Following explantation on day 28, the anterior tibia was processed for bacterial culture. The posterior tibia and rod were used for measuring bone-implant contact using micro-CT and for histopathology. Results of the experimental groups were compared to the Gel group results. The blood values in the Van2 and Van5 groups were lower on day 7. Moreover, culture results demonstrated less animals with an infection in both groups at day 28. In accordance, these groups showed lower grades for infection. Further, the Van2 group demonstrated more bone-implant contact. These results suggest that infection was reduced in the Van2 and Van5 groups. In contrast, blood values, histological grades, and bone-implant contact of the BAG and NAC groups were comparable with the Gel group. These results suggest that infection was not prevented in the BAG and NAC groups. Local application of vancomycin-loaded DAC-hydrogel successfully reduced implant-related infections. Loading of the hydrogel with BAG or NAC did not prevent infection. It is possible that BAG in powder form, as used in the present study, dissolved before the antibacterial effect could take place. Instead, BAG granules may be a viable alternative. Next, it is possible that the NAC concentration was too low to prevent infections in an in vivo environment, although this concentration was proven effective in vitro for its antibacterial properties

Aim. Local antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine. With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ. Method. The bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation. The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate. Results. The mean concentration of CFZ in the eluate obtained from BC type A incubated for 2h was higher compared to BC type B, respectively 581 mg/l and 297 mg/l. However, the elution profile is the same for both types: the CFZ concentration in the eluates drops within the first 24h from 581 mg/l to 365 mg/l (37%) for BC type A and from 297 mg/l to 132 mg/l (56%) for BC type B. After 24h no further significant CFZ release is seen. Impregnation of the bone chips before or after gamma irradiation did not affect this elution profile. Conclusions. Bone chips treated with scCO2 show a comparable elution pattern compared to non-scCO2 treated bone chips. AB release depends on the properties of the AB, making it impossible to copy the same impregnation protocol for different antibiotics. The stability of CFZ in solution at 37°C and its release are a major concern when establishing an impregnation protocol with CFZ

Prosthetic joint infections (PJI) are amongst the most feared postoperative complication of total joint replacement (TJR). PJIs are associated with significant morbidity ranging from functional impairment to amputation. Staphylococcus aureus (S. aureus) is one of the most common causative organisms involved in PJI. More than one quarter of the general population are S. aureus carriers, and carrier status has been shown to increase the risk of developing surgical site infections including PJIs. Decolonization of S. aureus carriers prior to surgery has demonstrated promising results in general surgery, however, solid evidence supporting decolonization in orthopaedic patients is lacking. We aimed to seek further evidence supporting pre-operative screening and S. aureus decolonization in patients undergoing primary or revision hip and knee TJR. A quasi-experimental quality improvement study was conducted to compare the 5-year baseline rates of deep PJIs to a one-year screening and decolonization intervention period. All consecutive patients who underwent primary or revision TJR at one tertiary care hospital in Hamilton, ON, Canada were included in both study periods. Nasal and throat screening for S. aureus carriage of all eligible TJR patients in the preoperative clinic was implemented as standard of care. Patients who tested positive were contacted and provided with details on the S. aureus decolonization protocol. Decolonization included a standardized treatment protocol of 2% intranasal mupirocin twice daily for five days prior to surgery date (excluding day of surgery), and chlorhexidine gluconate wipes (2%) to be used once daily for 4 days prior to surgery date and on the morning of surgery. Regardless of the colonization status at the visit in the preoperative clinic, all patients were re-swabbed on the day of surgery. Primary outcome of interest was the rate of deep PJI as per CDC/NHSN at one-year postoperative follow-up. Secondary outcomes included rate of deep PJIs due to S. aureus, adherence to the decolonization protocol, proportion of S. aureus carriers successfully decolonized, and the proportion of patients deemed as non-carriers following preoperative swab subsequently identified as carriers on the day of surgery. A total of 8,505 patients were included in the 5-year control group, and 1,883 during the intervention period, of which 424 (22.5%) were identified as S. aureus carriers. The deep PJI rate was similar in the two groups, 0.4% (7/1,883) in the intervention group and 0.5% (42/8,505) in the control group (OR 0.75, 95%CI 0.34–1.67, p=0.58). More importantly, we found a significant reduction in PJI due to S. aureus to only one case in the intervention period (0.05%) as compared to 29 cases (0.3%) in the historic control (OR 0.15, 95%CI 0.004–0.94, p=0.0376). We found a significant reduction in PJIs due to S. aureus by decolonizing S. aureus carriers prior to surgery. However, no significant difference in overall infection rates was observed. In conclusion, routine implementation of active screening for S. aureus and decolonization of carriers before TJR is feasible and helps to reduce PJI due to S. aureus

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. Chronic bone infections and infected fractures are often treated with excision of the dead bone and implantation of biomaterials which elute antibiotics. Gentamicin has been a preferred drug for local delivery, but this could induce renal dysfunction due to systemic toxicity. This is a particular concern in patients with pre-existing chronic renal disease treated with new antibiotic carriers which achieve very high peak levels of gentamicin in the first few days after surgery. Method. 163 patients (109 males; average age 51.6 years) with Cierny-Mader Type 3 or 4 chronic osteomyelitis had a single-stage operation with excision of the dead bone, filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier, containing gentamicin and immediate soft tissue closure. 2. No patient was given systemic gentamicin or other renal toxic antibiotics. Mean carrier volume was 10.9mls (range 1–30mls) and mean gentamicin dosing was 190.75mg (maximum 525mg). Seven patients had pre-existing renal disease (4 diabetic nephropathy, 1 nephrotic syndrome, 1 renal transplant and 1 previous acute kidney injury). Serum creatinine levels were collected pre-operatively and during the first seven days post-operatively. Glomerular filtration rate (GFR) was calculated using the CKD-epi creatinine equation. Renal function was defined using the Chronic Kidney Disease (CKD) Staging system. Results. 155 cases had adequate data to allow calculation of pre- and post-operative GFR. Pre-operative CKD staging demonstrated 118 Class I (normal renal function), 30 Class II, 3 Class IIIa, 3 Class IIIb, and 1 Class V disease. Mean pre-operative GFR (99.7ml/min/1.73m. 2. , SD 21.0) was no different to post-operative GFR (103.2ml/min/1.73m. 2. , SD 21.3), p= 0.0861. Four cases had a >10% decline in GFR below normal, with only one case dropping a CKD stage, from I (normal) to II (mildly decreased). Only 1/7 cases with pre-existing renal disease had a GFR drop of >10% (from 11ml/min/1.73m. 2. to 8ml/min/1.73m. 2. ). 70/155 (45.2%) had a temporary GFR drop post-operatively, with the biggest drop occurring a mean 3.06 days following surgery (SD 2.1). No patient had clinical signs of new acute renal impairment post-operatively. Conclusions. Renal function is not significantly affected by local implantation of gentamicin up to 525mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy

Introduction. The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity. We aim to establish the risk of renal injury with local delivery in a ceramic carrier. Materials and Methods. 163 consecutive patients with Cierny-Mader Type 3 or 4 chronic osteomyelitis were treated with a single-stage operation which included filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. The mean carrier volume used was 10.9mls, leading to a mean implanted gentamicin dose of 191.3mg (maximum 525mg). Serum creatinine levels were collected pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the Chronic Kidney Disease (CKD) Staging system, and AKI was assessed using the RIFLE criteria. Results. 155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 patients had pre-existing renal disease. 70 patients (45.2%) had a temporary eGFR drop post-operatively, with the greatest decrease occurring a mean 3.06 days following surgery. Twenty cases had a >10% decline in eGFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. Conclusions. The implantation of up to 525mg of gentamicin contained within Cerament G, as part of the surgical treatment of osteomyelitis, is safe and carries minimal risk of significant acute kidney injury. A small, transient increase in serum creatinine may be observed in the early post-operative period, and attention should be paid to limit patients exposure to other nephrotoxic agents. The majority of patients will return to their baseline renal function within 7 days following the operation. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy

Aims. Dead space management is an important element in the surgical management of chronic osteomyelitis and can be addressed with the use of a biodegradable local antibiotic carrier. We present the clinical and radiographic outcomes in two different biodegradable antibiotic carriers used in the management of chronic osteomyelitis. Method. A single centre series reviewed between 2006–2017. The initial cohort (2006–2010) of 180 cases (Group A) had a calcium sulphate carrier containing tobramycin (Osteoset. ®. T, Wright Medical). The second cohort (2013–1017) of 162 cases (Group B) had a biphasic calcium sulphate, nano-crystalline hydroxyapatite carrier containing gentamicin (Cerament. TM. G, Bonesupport AB). All cases were Cierny-Mader Grade III and IV and had a minimum of one-year clinical follow-up. Clinical outcomes reviewed included infection recurrence rate, wound leak, and subsequent fracture involving the treated segment. All cases with a minimum one-year radiographic follow-up were reviewed and bone void filling was assessed as percentage filling on the final follow-up radiograph to the nearest five percent increment. Results. Mean follow-up in Group A was 4.2 years (range 1.3–10.5 years) and in Group B it was 1.8 years (1–4.7 years). Group A had a significantly higher rate of infection recurrence (19/180 (10.6%) Vs. 7/163 (4.4%) p=0.030), wound leak (33/180 (18.3.%) Vs. 16/162 (9.9%) p=0.026) and subsequent fracture rate (11/180 (6.1%) Vs. 3/162 (1.9%) p=0.047) compared to Group B. Of the cases with a minimum of one-year radiographic follow-up Group A had 96 cases (mean follow-up 3.3 years, range 1.0–10.5 years) and Group B had 137 cases (mean follow-up 1.6 years, range 1.0–4.7 years). The mean bone void healing in Group B was significantly better than Group A (74.0% Vs. 41.7%, p <0.00001). Conclusions. Cerament. TM. G has significantly better bone healing compared to a calcium sulphate carrier and was associated with a lower rate of recurrent infection, wound leak and subsequent fracture risk

Aim. Prosthetic joint infection (PJI) is a major complication in THA. Nasal carriage with S. Aureus is a well-defined risk factor for infection in hospitalized patients. Risk for infection is reduced up to 50% by eradication therapy. Since PJI rates are very low and only 25% of the population are carriers, significant differences are hard to show and reports on PJI have been inconclusive. We analysed the effect of S. Aureus eradication therapy in THA. Methods. From 2011, patients receiving THA are screened for S. Aureus carriage and carriers are treated. This group was retrospectively compared with a historical THA group in which no screening and eradication therapy was done. We assumed similar carrier rates in both groups and calculated the risk reduction of eradication therapy for PJI in comparison to the historical carriers without treatment. Fisher's Exact test was used to compare outcome. Results. 2072 patients were screened and 478 patients were positive (23%). The historical control group consisted of 1248 patients, with 288 calculated carriers (23%). 15 PJI (0.72%) occurred vs 14 (1.12%) in the historical group (p=0.16). A 52% reduction in S. Aureus infections was found (0.33% vs 0.64% p=0.15). Infection rates for PJI caused by S. aureus was similar in non-carriers and carriers after eradication therapy (0.3 vs 0.4% p=0.506). The calculated infection rates in carriers in the historical group was reduced from 2.6% to 0.8% (RR 3,25, p=0.07) by eradication therapy and from 1.7% to 0,4% (RR 4,25, p=0.07) for S. Aureus PJI. Conclusions. A clear trend in reduction of PJI was demonstrated as a result of S. aureus screening and eradication therapy, reducing the rate of PJI for carriers to the same level as non-carriers

The goals of the present study are to describe the prevalence of both methicillin sensitive and resistant S.aureus carriage among elective total hip and knee arthroplasty candidates and to evaluate the real impact of preoperatively treating carriers in preventing prosthetic joint infection. Patients undergoing elective primary THA or TKA at a single institution were enrolled in a prospective randomized trial. S.aureus nasal carriage screening was performed in the outpatient setting and selected carriers underwent a 5-day preoperative treatment of nasal mupirocin and chlorhexidine bathing. All patients were followed regularly in the outpatient clinic. No patients were lost to follow-up at a minimum of one year after surgery. The main outcome of the study was the diagnosis of prosthetic joint infection occurring in the first year after surgery including all pathogens and a secondary outcome was defined as infections involving S.aureus bacteria only. From January 2010 to December 2012, 1305 total joint arthroplasties were performed and 1028 of those were screened. We observed a 22.2% (228/1028) S.aureus colonization rate and only eight patients colonized with MRSA (0.8%). Twenty five cases of prosthetic joint infections were identified with an overall infection rate of 2.4%. S.aureus was involved in 14 cases. PJI rate in S.aureus carriers was 3.9% (9/228), which was not significantly higher than the 2.0% (16/800) found among non carriers. Treated and untreated carriers infection rate also showed no significant differences – 3.4% (3/89) vs. 4.3% (6/139). Multivariable analysis substantiates ASA≥ 3 (OR=3.42, 95% CI=1.51 – 7.74) and duration of surgery above the 75th percentile (OR=2.74, 95% CI=1.22 – 6.16) as independent predictors of PJI but not S.aureus carrier state. We obtained similar results when considering infection involving S.aureus bacteria only. Of the 14 cases where S.aureus was present in PJI, only five were carriers preoperatively. Of those five cases, one was an untreated MSSA carrier that ultimately got an MRSA infection. Our results show no clear benefit in screening and decolonizing S.aureus nasal carriers before total joint arthroplasty. There seems to be a lack of causal relation between nasal S.aureus and PJI pathogen as most of S.aureus PJI seems to have an exogenous source

Aim. Excision of chronic osteomyelitis (cOM) creates a dead space which must be managed to avoid early recurrence of infection. Systemic antimicrobials cannot penetrate this space in high concentration so local therapy has become an attractive adjunct to surgery. This study presents the mid- long-term results of local therapy with gentamicin in a bioabsorbable ceramic carrier. Method. A prospective series of 100 patients with Cierny & Mader Types III and IV cOM, affecting 105 bones, were treated with a single stage procedure, including debridement, deep tissue sampling, local and systemic antimicrobials, stabilization and immediate skin closure. cOM was confirmed with strict diagnostic criteria. Patients were followed up for a mean of 6.05 years (range 4.2–8.4 years). Results. At final follow-up, 6 patients had evidence of recurrent infection (94% infection-free). 3 infections recurred in the first year, with 2 in the second year and one at 4.5 years after surgery. Recurrence was not dependent on host physiological class (1/20 Class A; 5% vs 5/80 Class B; 6.25%. p=0.833). Nor was it related to aetiology of the infection, microbial culture or the presence of an infected non-union before surgery (1/10 with non-union; 10% vs 5/90 without non-union; 5.6%. p=0.57). Organisms which demonstrated intermediate or high-grade resistance to gentamicin were more likely in polymicrobial infections (9/21; 42.8%) compared to single isolate osteomyelitis (7/79; 8.9%)(p<0.001). However, recurrence was not more frequent when a resistant organism was present (1/16; 6.25% for resistant cases vs 5/84; 5.95% in sensitive culture infection) (p=0.96). Conclusions. This study shows that the single stage protocol, including a high delivery local antibiotic ceramic, was effective over several years. The method can be applied to a wide range of patients, including those with significant comorbidities and infected non-union

Osteomyelitis caused by resistant bacterial strains can be dealt with antimicrobial agents which have a different mode of action compared to antibiotics. A very promising appears to be antimicrobial peptides (AMPs). We found and verified in vitro experiments that one of the most effective and least toxic antimicrobial peptides are contained in the wild bee venom. The aim of this study was to verify the efficacy of topically applied, synthetically prepared antimicrobial peptide (Hal 2/27) with carrier, originally isolated from the venom of the wild bee in experiments on laboratory rats. It was used 18 rats, which were indicated osteomyelitis of the left femurs. After a week of six rats were injected calcium phosphate carrier with AMP Hal 2/27, six rats received only a carrier without AMP and six other rats remained without further intervention. After a week, rats were sacrificed and X-ray was performed in all rats limbs. Rats who received carrier with AMP Hal 2/27 had less X-ray evidence of osteomyelitis of femurs compared to rats after administration of the carrier without AMP. Topical application of a new synthetic antimicrobial peptides isolated from wild bee venom (Hal 2/27) using local carriers seems to be a promising way to treat and prevent infectious complications in orthopedics and traumatology. Internal grant of University Hospital Motol, Advanced Therapies, NO: 9777 and Internal grant of University Hospital Motol, NO 6010

Background. Hospital acquired MRSA is globally endemic and is a leading cause of surgical site infection (SSI). Of great concern is the emergence of community acquired MRSA (CA MRSA) with its unique virulence characteristics. Infected hip or knee prostheses due to MRSA are associated with multiple reoperations and prolonged hospital stay. Few studies have been done to assess for risk of SSI in MRSA carriers undergoing elective orthopaedic surgery following decolonisation. However in these studies, the eradication status was not confirmed prior to proceeding for surgical intervention. Aim. The purpose of the study was to evaluate the incidence of SSI in MRSA carriers undergoing elective hip and knee arthroplasty, who had confirmed eradication of MRSA carrier status and to compare it with incidence of SSI in non MRSA carriers. Material and Methods. This is a retrospective analysis of 6613 patients who underwent elective hip (3347) and knee arthroplasty (3266) at our institution between January 2008 and August 2012. A cohort of patients who were preoperatively colonised with MRSA was identified. These patients were offered decolonisation protocol and successful eradication was ensured prior to surgery. The MRSA negative patients served as the control group and we looked into the incidence of SSI in both groups up to one year after surgery. Categorical variables were investigated between groups using chi-squared tests and p value of < 0.05 was taken as significant. Results. Out of 6613 patients, MRSA colonisation was observed in 83 patients (a mean age of 76 years with a M:F ratio of 1:1.2) pre-operatively with a colonisation rate of 1.3%. A total of 79 patients had confirmed eradication of carrier status prior to surgical intervention. Of these 38 were THRs and 41 were TKRs. Total number of MRSA negative patients were 6530 with 3307 THRs and 3223 TKRs in control group. Teicoplanin was used for antibiotic prophylaxis in these patients. 5 of 79 patients had “deep SSI” within 1 year of surgery giving an infection rate of 6.32%. There were 2 MRSA infections in hip replacements with an infection rate of 5.26%. There were 2 MRSA and 1 MSSA infection in TKR resulting in an infection rate of 7.31%. These patients did not belong to the “high-risk” group for MRSA colonisation. A significant statistical difference in infection rates from MRSA negative control group was noted, which had a deep sepsis rate of 1.17% (p value − 0.03) in THRs and 0.87% in TKRs (p value − 0.0016). Conclusions and Clinical Implication. In spite of a selective treatment program for carriers and confirmed eradication in terms of achieving a reduction in the rate of SSI, there is still a significantly increased risk of SSI in MRSA colonised patients undergoing hip and knee replacements. Also, should infection develop, MRSA is the most likely causative organism. Patients should be made aware of this higher risk of infection and the serious consequences of developing MRSA SSI

Aim. Fracture-related infection (FRI) is a challenging complication. This study aims to investigate (1) microbial patterns in fracture-related infection (FRI), (2) the comparison of isolated pathogens in FRI patients with early, delayed, and late onset of infection and (3) antibiotic susceptibility profiles to identify effective empiric antibiotic therapy for FRI. Method. Patients treated for FRI from 2013 to 2020 were grouped into early (< 2 weeks), delayed (2– 10 weeks) and late (> 10 weeks) onset of infection. Pathogens detected during treatment were evaluated for pathogens. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. Results. In total 117 patients (early n=19, delated n=60, late n=38) were included in the study. Infection was polymicrobial in 10 cases (8.6%) and culture-negative in 11 cases (9.4%). Staphylococcus aureus was the most frequently detected pathogen (40.5%), followed by Staphylococcus epidermidis (17.2%) and gram-negative bacteria (16.4%). Pathogen distribution did not differ statistically significant between the groups. Highest effectiveness could be achieved by the combination of meropenem + vancomycin (95.7%) and gentamycin + vancomycin (94.0%). More than 90% of all patients would have also been covered by co-amoxiclav + glycopeptide (93.2%), ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide (92.3% each) as well as ceftriaxone + glycopeptide (91.5%). Comparing the predicted efficacy of empiric antimicrobial regimens between the subgroups only revealed a statistically significant difference regarding the combination ciprofloxacin with a glycopeptide (F= 3.304, p=.04), for which more patients with an early onset of infection would have been susceptible. Conclusions. Microbiological pattern for the causative microorganism between early, delayed, and late FRI are comparable. Empiric therapy combinations such as meropenem + vancomycin, gentamycin +vancomycin or co-amoxiclav + glycopeptide are effective antibiotic strategies. To bypass unwanted side effects of systemic antibiotics and reduce the risk of antimicrobial resistance, the administration of local antibiotic carriers should be implemented in clinical practice

Aim. The aim of this systematic review was to determine all cultured bacteria, antibiotic strategies, and their outcome from literature describing treatment of FRI patients between 1990 and 2018. Methods. A systematic literature search was performed on treatment and outcome of FRI. All studies in English that described surgical patient series for treatment of FRI were included, using Medline, Embase, Web of Science, Cochrane, and Google Scholar. Publications before 1990 and studies that did not describe FRI patient treatment or did not report original data (e.g., reviews or meta-analyses) were excluded. Study selection and data collection were done by two authors independently. Main collected parameters were preoperative cultures, use of local antibiotics, postoperative antibiotic protocol, cultured microorganisms, and overall outcome of treatment, i.e., eradication of infection and bony union, recurrence, amputations, revisional surgery, and number of complications. Dichotomous data were pooled using Medcalc, and weighted means were calculated for continuous data using Excel. Results. 2,171 studies were identified. Of these, 110 studies were included, describing 119 patient series, in which 4561 patients (4614 fractures) were treated. The population was predominantly male (76%), and the main location of FRI was the tibia (69%). In 78 (71%) studies, 3,234 microorganisms were cultured, of which Methicillin-sensitive Staphylococcus aureus (MSSA) was found in 1,094 (34%) patients, followed by Coagulase-negative Staphylococci (CNS), 431 (13%), Methicillin-resistant Staphylococcus aureus (MRSA), 283 (9%), and Pseudomonas aeruginosa 276 (9%). Polymicrobial infections were present in 11% of patients. Local antibiotics were used in 63 (53%) patient series, with PMMA being the most frequent carrier (73%). Calcium-based cements were used in nine series (14%). Clear postoperative antibiotic protocols were described in only 39 (35%) studies and differed widely. Bony union and infection eradication were achieved in 92% (CI 90–94) of all patients. Recurrence was seen in 9% (CI 8–11), and amputation was required in 3% (CI 3–4) of patients. The effect of local antibiotics on overall outcome of FRI treatment was unclear. Conclusions. This systematic literature review clearly shows that standardized antibiotic treatment protocols for FRI patients are lacking and that internationally accepted guidelines are required. The data also confirm that S. aureus is the most common microorganism encountered in FRI. Due to the large heterogeneity of used local antibiotics and carriers, a reliable comparison was not feasible. Indications for the use of local antibiotics are unclear, and future prospective studies seem necessary

Aim

Knee arthrodesis (KA) and above knee amputation (AKA) have been used for salvage of failed total knee arthroplasty (TKA) in the setting of periprosthetic joint infection (PJI). The factors that lead to a failed fusion and progression to AKA are not well understood. The purpose of our study was to determine factors associated with failure of a staged fusion for PJI and predictive of progression to AKA.