Objectives. As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. Methods. A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis. Results. In total, eight studies which included 2738 patients were eligible for quantitative synthesis. The effect of antibiotic-loaded poly(methyl methacrylate) beads was investigated by six of these studies, and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.6%; 91/1986) than in the control group receiving standard systemic prophylaxis alone (16.5%; 124/752) (p < 0.001) (odds ratio 0.30; 95% confidence interval 0.22 to 0.40). Conclusion. This meta-analysis suggests a risk reduction in FRI of 11.9% if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity, and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution. Cite this article: M. Morgenstern, A. Vallejo, M. A. McNally, T. F. Moriarty, J. Y. Ferguson, S. Nijs, WJ. Metsemakers. Bone Joint Res 2018;7:447–456. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

Aim. Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. Method. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST). Results. Local antibiotics were used in 74/125 (59.2%) of patients. Agents used were Gentamicin 53/125 (42.4%), Tobramycin 18/125 (14.4%), and vancomycin in 19/125 (15.2%). Combined gentamicin and vancomycin usage was seen in 16/125 patients (12.8%). Gentamicin non-sensitivity was common in this cohort with frequent aminoglycoside use. At index procedure, a Gentamicin non-sensitive organism was cultured in 51/125 patients (40.8%). At re-operation this proportion was lower: 40/125 (32%). There was no statistically significant difference in the rate of Gentamicin resistance at reoperation comparing patients who previously received local aminoglycosides with those who had not (21/71, 29.8% vs 19/54, 35.2% p=0.6, chi-squared test). In 48/125 (38.4%) of patients, the same species was isolated during the index and recurrence surgery. We identified 7 cases with new aminoglycoside resistance arising at the second procedure. In 2/7 – S. aureus and E. faecalis - aminoglycoside resistance was the only change in antimicrobial sensitivity. In 5/7, there were at least 2 additional changes in observed antimicrobial sensitivity. 3/74 (4%) of cases who initially received local aminoglycoside cultured organisms with aminoglycoside resistance at recurrence. 4/51 (7.8%) of those who did not receive local or systemic aminoglycoside at index surgery cultured resistant organisms (chi square 0.82; p=0.365). Conclusions. As a group, patients whose treatment for orthopaedic infection included local antibiotics did not exhibit higher rates of specific antimicrobial resistance compared with those not treated with local antibiotics. However we did identify cases where Gram positive bacteria developed aminoglycoside resistance regardless of their initial antimicrobial therapy. This should be considered in antimicrobial choice during surgery for recurrence

Despite the routine use of systemic antibiotic prophylaxis, postoperative infection following fracture surgery remains a persistent issue with substantial morbidity. The use of additional local antibiotic prophylaxis may have a protective effect and some orthopaedic surgeons have adopted their use in recent years, despite limited evidence of its beneficial effect. The purpose of this systematic review and meta-analysis was to evaluate the current literature regarding the effect of prophylactic local antibiotics on the rate of infection in fracture surgery in both open and closed fractures. A comprehensive search of Medline, EMBASE, and PubMed was performed. Cohort studies were eligible if they investigated the effect on infection rate of additional local antibiotic prophylaxis compared with systemic prophylaxis alone following fracture surgery. The data were pooled in a meta-analysis. In total, four randomized controlled trials and 11 retrospective cohort studies with a total of 6161 fractures from various anatomical locations were eligible for inclusion. The majority of the included studies were Level 3 evidence and had a moderate risk of bias. When all fractures were pooled, the risk of infection was significantly reduced when local antibiotics were applied compared with the control group receiving systemic prophylaxis only (OR = 0.39; 95%CI: 0.26 to 0.53, P < 0.001). In particular, there was a significant reduction in deep infections (OR = 0.59; 95%CI: 0.38 to 0.91, P = 0.017). The beneficial effect of local antibiotics for preventing total infection was seen in both open fractures (OR = 0.35; 95%CI: 0.23 to 0.53, P < 0.001) and closed fractures (OR = 0.58; 95%CI: 0.35 to 0.95, P = 0.029) when analyzed separately. This meta-analysis suggests a significant risk reduction for postoperative infection following fracture surgery when local antibiotics were added to standard systemic prophylaxis, with a protective effect present in both open and closed fractures

Aim. Alongside debridement and irrigation, soft tissue coverage and osseous stabilization, systemic antibiotic prophylaxis is considered the gold standard in the management of open fractures and considerably reduces the risk of subsequent fracture-related Infections (FRI). The direct application of antibiotics into the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. Method. A comprehensive literature search was performed in PubMed, Web-of- Science and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared to systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis. Results. Eight studies, with a total of 2738 patients were eligible for quantitative synthesis. Six of these studies investigated the effect of antibiotic loaded PMMA beads and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.7%;94/1996) than in the control group receiving standard systemic prophylaxis alone (16.2%;129/797) (p-value < 0.001) (OR 0.30; 95%CI 0.22–0.40). Conclusions. This meta-analysis suggests a clear risk reduction in FRI if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100

Aims. Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery. Materials and Methods. Databases were searched to identify eligible studies and 13 were identified for inclusion. Results. Overall, the quality of the studies was poor. A single trial suggested that wound healing is quicker when a gentamicin-impregnated collagen sponge was implanted at time of surgery, with no difference in length of stay or rate of amputation. Results from studies with high risk of bias indicated no change in wound healing when a gentamicin-impregnated sponge was implanted during transmetatarsal amputation, but a reduction in the incidence of wound breakdown (8% vs 25%, not statistically significant) was identified. A significant cost reduction was identified when using an antimicrobial gel to deliver antibiotics and anti-biofilm agents (quorum-sensing inhibitors) compared with routine dressings and systemic antibiotics. Analyses of case series identified 485 patients who were treated using local antibiotic delivery devices. The rates of wound healing, re-operation, and mortality were comparable to those that have been previously reported for the routine management of these infections. Conclusion. There is a lack of good-quality evidence to support the use of local antibiotic delivery devices in the treatment of foot infections in patients with diabetes. Cite this article: Bone Joint J 2018;100-B:1409–15

Infection is still a major problem in implant surgery. Most infections are caused by bacteria that enter the wound at the time of the operation. Although prophylactic antibiotics given intravenously have been shown to be effective if given during the correct time frame, the concentration of local antibiotics in the knee in response to intravenous antibiotics is about 1/3 that achieved in the serum, and the level is transient. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and costs analysis shows a remarkable monetary benefit to this effect. Local antibiotic irrigation during implant surgery is inexpensive, easy, and effective

Infection is still a major problem in implant surgery. Most infections are caused by bacteria that enter the wound at the time of the operation. Although prophylactic antibiotics given intravenously have been shown to be effective if given during the correct time frame, the concentration of local antibiotics in the knee in response to intravenous antibiotics is about 1/3 that achieved in the serum, and the level is transient. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and costs analysis shows a remarkable monetary benefit to this effect. Local antibiotic irrigation during implant surgery is inexpensive, easy, and effective

A multimodality approach is needed for management of infected joint replacement prostheses and infected skeletal metalwork. We present our results in six patients managed surgically with standard techniques, with the addition of a local antibiotic delivery system using absorbable Calcium Sulphate beads. A retrospective study was undertaken of 6 patients with established musculoskeletal infection in relation to existing metalwork. Two patients had infection in the hip replacement prosthesis, three had infected prosthetic knee joints and one had infection in a femoral locking plate. All were treated with extensive debridement, revision / retention of implants, parenteral antibiotics and local antibiotics. Patients were followed up in clinic for resolution of inflammatory markers and subsidence of signs of infection. Control of infection was achieved in five patients at average 19 months followup. One patient had persistent infection and has undergone further surgery. In this preliminary study, we found local antibiotic delivery using absorbable calcium sulphate beads to be an effective adjuvant to standard debridement, parenteral antibiotics and revision of implants

Introduction. Management of open fractures is challenging and requires a multidisciplinary team approach. Gustilo Anderson Type IIIB fractures reportedly have a higher infection rate (up to 52%) and up to 16% amputation rate. This study aims to evaluate outcomes of using Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite in management of Open Gustilo-Anderson IIIB fractures. Materials and Methods. We reviewed a prospective data of 80 patients who presented with Gustilo Anderson Type IIIB Open Fracture to a single ortho-plastic centre. Only patients who were managed with single-stage “Fix and Flap” along with intra-operative Adjuvant Local Antibiotic Bio-Composite were included. Results. Mean follow-up time was 22 months. The mean time from injury until definitive surgery was 7.73 days (1–30 days). Primary union achieved in 88.3% within 32 weeks on average. The delayed union reported in 7.8% of patients, for the bone healing stimulated by injecting the fracture site with Autologous Bone Marrow Aspirate Concentrate. Subsequent follow-up showed signs of successful fracture healing at 60 weeks post-injury. Three patients (3.9%) had non-union. Limb salvage rate was 96.25%, and only 1.25% deep infection rate. Conclusions. Our results highlight that low infection rates, high limb salvage rates and high union rates can be achieved in these complex injuries with a combined OrthoPlastic approach, MDT input, meticulous technique and the use of adjuvant local antibiotic bio-composite. Delay in definitive surgery, gentamicin resistance and smoking were not associated with any increased deep infection or non-union in our series. At 22 months of follow-up, deep infection rate was 1.25%, limbs salvage rate was 96.25%, fracture union rate was 96.1%, and reoperation rate 18.75%

For local antibiotic therapy gentamycin is in clinical use since many years, originally in the form of PMMA beads, later also in the form of resorbable collagen fleece. A prospective study comparing the efficacy of both application forms so far is missing. In a prospective study 108 patients with chronic sclerosing osteomyelitis were treated by a standardised operative debridement protocol. The debrided cavities were filled with 54 patients (group 1) were treated by local antibiotic beads (Septopal) and 54 patients (group 2) by local resorbable antibiotic fleece (Sulmycin). Both groups were comparable concerning age, location, duration of operation, type of osteomyelitis and predisposing factors. The mean follow-up was 6.1 years (range 3.8 – 9.3). Evaluation was done for the re-operation rate, CRP and ESR, white blood cells and local wound healing criteria. Twenty-six patients (44 per cent) underwent one or more revision operations because of persistent infection. In group I 67 per cent and in group II 20 per cent (p = 0.0001). No difference was noted for CRP (p = 0.46), ESR (p = 0.09), white blood cells (p = 0.24) and local wound healing criteria (p =0.34). After local gentamycin fleece application the early re-operation rate is significantly lower compared to gentamycin beads. After a treatment period of 3 month this difference disappears

Aims. The use of local antibiotic carriers in the treatment of chronic osteomyelitis is an important adjunct in dead space management. We present the outcomes of two different biodegradable antibiotic carriers used in the management of chronic osteomyelitis. Method. A single centre series between 2006–2017. The initial cohort (2006–2010) of 137 cases, Group A, had Osteoset® T (calcium sulphate carrier containing tobramycin). The second cohort (2013–1017) of 160 cases, group B, had CeramentTM G (biphasic calcium sulphate, nano-crystalline hydroxyapatite carrier containing gentamicin). Only Cierny-Mader Grade III and IV cases were included with a minimum six-month radiographic follow-up. Infection recurrence rate, wound leakage, subsequent fracture involving the treated segment, and radiographic void filling were assessed at a minimum of 6 months following surgery. Results. Mean follow-up in Group A was 2.5 yrs (0.5–10.5) and in Group B it was 1.4 yrs (0.6–4.7). Group A had a significantly higher rate of infection recurrence (16/137 (11.7%) Vs. 7/160 (4.4%) p=0.0278), wound leakage (26/137 (19.0%) Vs. 16/160 (10.0%) p=0.0304) and subsequent fracture rate (11/137 (8.0%) Vs. 3/160 (1.9%) p=0.0143) compared to Group B. Average time to recurrence was 1.07 years (0.1–2.6) in Group A and 1.02 (0.2–2.1) in Group B. The mean bone void healing in Group B was significantly better than Group A (73.2% Vs. 40.0%, p <0.00001). Conclusions. Cerament™ G has significantly better bone healing compared to a calcium sulphate carrier and was associated with a lower rate of recurrent infection, wound leakage and subsequent fracture risk

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

We reviewed 1085 consecutive compound limb fractures treated in 914 patients at the University of Louisville over a nine-year period. Of these fractures, 240 (group 1) received only systemic antibiotic prophylaxis and 845 (group 2) were managed by the supplementary local use of aminoglycoside-polymethylmethacrylate (PMMA) beads. There were no significant differences in age, gender, fracture type, fracture location or follow-up between the two groups. All had copious wound irrigation, meticulous debridement and skeletal stabilisation, but wound management and the use of local antibiotic depended on the surgeon's individual preference and there was no randomisation. In group 1 there was an overall infection rate of 12% as against 3.7% in group 2 (p < 0.001). Both acute infection and local osteomyelitis showed a decreased incidence in group 2, but this was statistically significant only in Gustilo type-IIIB and type-IIIC fractures for acute infection, and only in type-II and type-IIIB fractures for chronic osteomyelitis. Our review suggests that the adjuvant use of local antibiotic-laden PMMA beads may reduce the incidence of infection in severe compound fractures

Introduction: Purified plaster of Paris can be used as a resorbable carrier material for local antibiotic therapy. Clinical use already has been published with vancomycin and the aminoglycosides gentamycin and tobramycin. Calcium sulphate pellets with vancomycin can be manufactured during operation from Osteoset. ®. and vancomycin powder, whereas calcium sulphate with tobramycin is available as ready-to-use pellets under the brand name Osteoset T. ®. Results are promising. However, no data on systemic serum levels in humans have been published so far, despite well known toxicity issues of these antibiotics in systemic therapy. Methods: Following implantation of calcium sulphate with vancomycin or tobramycin, systemic serum levels of these antibiotics have been measured for up to 10 days, and prospectively gathered. Considering serum levels and renal function, pharmacokinetics have been estimated. Results: Between August 2006 and February 2008, calcium sulphate with vancomycin has been implanted in 15 patients, and with tobramycin in 12 patients. Whereas vancomycin levels remained very low, tobramycin levels close to the usually accepted trough levels could be observed at 24h post-operation. Conclusion: Vancomycin added to calcium sulphate has a safe systemic profile. On the contrary, significant serum levels of tobramycin can be measured more than 24h after implantation. Caution is mandatory when using this antibiotic, and explantation should be considered if levels too high are observed

An extensive review of the spinal and arthroplasty literature was undertaken to evaluate the effectiveness of local antibiotic irrigation during surgery. The efficacy of antibiotic irrigation for the prevention of acute post-operative infection after total joint arthroplasty was evaluated retrospectively in 2293 arthroplasties (1990 patients) between January 2004 and December 2013. The mean follow-up was 73 months (20 to 139). One surgeon performed all the procedures with minimal post-operative infection.

The intra-operative protocol included an irrigation solution of normal saline with vancomycin 1000 mg/l and polymyxin 250 000 units/l at the rate of 2 l per hour. No patient required re-admission for primary infection or further antibiotic treatment. Two morbidly obese patients (two total hip arthroplasties) developed subcutaneous fat necrosis requiring debridement and one was revised because the deep capsular sutures were contaminated by the draining subcutaneous haematoma. One patient who had undergone total knee arthroplasty had unrecognised damage to the lateral superior geniculate artery and developed a haematoma that became infected secondarily four months after the surgery and underwent revision.

The use of antibiotic irrigation during arthroplasty surgery has been highly effective for the prevention of infection in the author’s practice. However, it should be understood that any routine prophylactic use of antibiotics may result in resistant organisms, and the wise stewardship of the use of antibiotics is an important part of surgical practice.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):23–6.

Aim

The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.

Background. Antibiotic-loaded cement has been used over decades as a local antibiotic delivery for the treatment of bone and joint infections. However, there were some disadvantages such as unpredictable elution, insufficient local concentration and reduced mechanical strength. We developed hydrophilized bone cement and investigated whether it can improve consistent antibiotic release for extended periods to be effective in eradicating joint infection without any changes of mechanical strength. Methods. The experiments consists of preparation of the hydrophilized, vancomycin-loaded bone cement, In vitro test including drug release behavior, mechanical properties by compression test, cytotoxicity, antibacterial effect and animal study. In animal study, Antibiotic cement rod was implanted in the femur of rat osteomyelitis model. Sign of infections were assessed by gross observation, Micro CT and blood analysis at indicated period. Results. The hydrophilized Vancomycin-loaded bone cements showed that continuous release of Vancomycin even over 6 weeks in the drug release test, sufficient mechanical strengths in the compression test and also better anti-bacterial effect compared to other commercially available bone cement. The animal study demonstrated that it has superior inhibition of bacterial proliferation according to imaging and blood analysis compared to control group. Conclusion:. As a results from both in vitro test and animal study, hydrophilized antibiotic bone cement may provide favorable environment to control bone and joint infection by continuous antibiotic release for extended period

Introduction

We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We hypothesized that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia.

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely utilised. Despite this, the long-term recurrence rate is approximately 25%. The aim of this cohort study was to examine the effectiveness of marginal surgical resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total. A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to stratify the patients further. There were 24 (48%) ‘A’ hosts and 26 (52%) ‘B’ hosts. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. The available pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels did not predict disease recurrence. Overall, the disease-free probability for this cohort was 0.80. A similar cohort treated with prolonged systemic and oral antibiotics reported by Simpson and colleagues (JBJS Br 2001) had a disease-free probability at 0.68. Local administration of gentamicin in a collagen fleece leads to improved disease-free probability when compared with prolonged systemic antibiotic treatment. We believe this is a useful component in the management of chronic osteomyelitis.

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842

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

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. . Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). . These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. Cite this article: Bone Joint J 2015;97-B:1423–7

Aim

Local concentration of antibiotic at the site of infection is a major parameter for its efficiency. However, bone diffusion is poor leading either to their non-use (ex: gentamicin) or the use of high concentration (ex: vancomycin). Local administration could optimize their local concentration combined with lower side effects. We report the clinical experience and pharmacological results of an antibiotic loaded porous alumina used to replace infected bone in 4 patients.

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Aims

Calcium sulphate (CaSO₄) 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 CaSO₄ as an adjunct to the routine therapy of bone and joint infections.

Background. Fracture-related infection (FRI) is treated by adequate debridement, lavage, fracture stabilization (if indicated), adequate soft tissue coverage and systemic antimicrobial therapy. Additional administration of local antibiotics (LA), placed directly in the surgical field, is thought to be beneficial for successful eradication of infection. Aims. 1) To evaluate the effect of local antibiotics on outcome in patients with FRI. 2) To evaluate whether bacterial resistance to the implanted local antibiotics influences its efficacy. Methods. A multinational cross-sectional study was performed in patients with FRI, diagnosed according to the FRI consensus definition, between January 2015 and December 2019. Patients who underwent surgical treatment for FRI at all time points after injury were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse Probability for Treatment Weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of LA and recurrence rate of FRI at 12 months, 24 months and final follow-up. Results. Overall, 433 FRIs in 429 patients were included. A total of 251 (58.0%) cases were treated with LA. Gentamicin was the most frequently used LA (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received LA and in 34/182 (18.7%) patients who did not. The use of LA reduced the recurrence rate of FRI at 12 months (HR: 0.69; 95% CI [0.24–1.96]) and 24 months (HR: 0.55; 95% CI [0.22–1.35]). Resistance of cultured microorganisms to the LA was not associated with a higher risk of recurrence of FRI (HR: 0.75, 95% CI [0.32–1.74]). Conclusion. The application of LA in treatment of FRI is likely to reduce the risk of recurrence of FRI as the risk reduction was consistent and clinically relevant but it did not reach statistical significance. High local antibiotic concentrations eradicate most pathogens regardless of susceptibility test results

Aim. This study investigated the effect of the choice of antibiotic regime on outcome of patients treated for fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. Method. All patients with FRI, confirmed by the FRI Consensus Definition. 1. and treated surgically, were included. Data were collected on patient characteristics, microbial cultures, antibiograms, empiric and definitive systemic antibiotic regimes and local antibiotic use. All patients were followed up for at least one year. The primary outcome was eradication of infection. The chosen antibiotic regimes were compared to the recent guidelines from the FRI Consensus Group. 2. , to assess the correlation with outcome. Results. 433 FRIs were treated in patients with mean age 49.7 years (range 14–84). Patients were followed up for a mean of 26 months (range 12–72). A microbiological diagnosis was obtained in 353 patients (18.5% culture negative rate), with 46% monomicrobial and 35.5% polymicrobial. Staph aureus was present in 51.3% of monomicrobial and 55.2% of polymicrobial infections. Negative cultures were much less likely in FRI within 10 weeks of injury (p=0.00001). Treatment failure with recurrent infection occurred in 13.6% of patients. Failure was more likely in culture positive cases (Polymicrobial; p=0.016, monomicrobial 0.039). Definitive antibiotic regimes were fully compliant with the FRI Guideline in 107 cases (24.7%). In 294 cases (68%) antibiotic regimes outside the guidelines were used. Non-compliance was often due to differences in recommended dosing or overtreatment with extra antimicrobials. 32 cases (7.4%) could not be assessed against the FRI Guidelines as the organisms or regimes were not represented in the guide. Failure rate with FRI Guideline compliant regimes was 12.1% and with non-compliant, 13.2% (p=0.87). Failure in unclassifiable cases was 21.9%. The use of local antibiotics reduced the recurrence rate from 18.3% without local antibiotics to 10.3% with local antibiotics (p=0.022). Conclusions. This study demonstrated that there can be considerable variability in the choice of antimicrobial regimes in FRI. Some deviations from the FRI Guideline did not result in poorer outcomes. These smaller differences in antimicrobial choice may not be major determinants of outcome

Introduction. The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates. Materials & Methods. A systematic review and meta-analysis were undertaken as per PRISMA guidelines. PROSPERO Registration CRD42022323545. PubMed, EMBASE, Scopus and CENTRAL were the databases assessed. The Newcastle Ottawa Scale and the Rob 2 Tool were used to assess bias. A qualitative synthesis of all included studies and meta-analysis of suitable subgroups was undertaken. Results. In total, 12 studies (11 observational, 1 RCT) assessing 2431 open fractures were included for analysis. All compared the addition of a local antibiotic therapy to a standard treatment versus the standard treatment alone. The methods of delivery were vancomycin powder (4 papers), tobramycin polymethylmethacrylate beads (4 papers), gentamicin coated intramedullary (IM) nails (2 papers), gentamicin injections (1 paper) and antibiotic released IM core cement (1 paper). The addition of vancomycin powder did not decrease infection rates in comparison to intravenous antibiotics alone (OR 1.3, 95% CI (0.75 – 2.26)). Antibiotic coated IM Nails appear to have an association with lower infection rates than standard IM Nails. PMMA antibiotics have shown varied results in reducing infection rates depending on the individual studies. Conclusions. There are numerous methods available to deliver antibiotics locally to an open fracture site. Further high-quality research is required to provide a definitive conclusion on their efficacy irrespective of delivery method

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well

Aim. This study investigated the management and clinical outcomes of patients treated for confirmed fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. Method. All patients with FRI, confirmed by the FRI Consensus Definition. 1. and treated surgically, were included. Data were collected on patient characteristics, time from injury to FRI surgery, soft tissue reconstruction, type of stabilization and use of local antibiotics. All patients were followed up for at least one year. The rates of eradication of infection and union were assessed. The associations between treatment methods, time from injury and outcomes were determined. Results. 433 FRIs were treated in patients with mean age 49.7 years (range 14–84). FRI affected the tibia in 226(52.2%), femur in 94(21.7%), pelvis in 26(6%), humerus in 20(4.6%) and foot bones in 19(4.4%). Patients were followed up for a mean of 26 months (range 12–72). Overall, eradication of infection was successful in 86.4% of cases and 86% of unhealed infected fractures were healed at final review. 3.3% required amputation. Successful outcome was not dependent on age, or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p=0.52). Method of stabilization had a major affect on outcome. Debridement and retention of a stable infected implant (DAIR) had a failure rate of 22.3%, implant exchange (to new internal fixation) 16.7%, conversion to external fixation 7.4%. DAIR was significantly worse than conversion to external fixation (p=0.01). There was no effect of the time from injury on the outcome of DAIR or any other fixation method. The use of a free flap in the tibia improved the success rate from 80.4% to 92.1% (p=0.044). Outcome was adversely affected by use of a split skin graft alone in soft tissue reconstruction (44% failure) (p=0.006). The use of local antibiotics reduced the recurrence rate from 18.3% to 10.3% (p=0.022). Conclusions. This study is the first to consider outcome for all FRIs, at all-time points, with all treatment modalities. Treatment was mostly successful but may be improved with better directed use of free flaps, local antibiotics, and limitation of DAIR. The results suggest that the division of FRIs into categories based on time from injury, may not be helpful with modern treatment

Aim. Pin site infection (PSI) is a common complication of external fixators. PSI usually presents as a superficial infection which is treated conservatively. This study investigated those rare cases of PSI requiring surgery due to persistent osteomyelitis (OM), after pin removal. Method. In this retrospective cohort study we identified patients who required surgery for an OM after PSI (Checketts-Otterburn Classification Grade 6) between 2011 and 2021. We investigated patient demographics, aetiology of the OM, pathogen and histology, treatment strategies and complications. Infection was confirmed using the 2018 FRI Consensus Definition. Successful outcome was defined as an infection-free interval of at least 24 months following surgery, which was defined as minimum follow-up. Results. Twenty-seven patients were treated due to a pin site infection with an osteomyelitis (22 tibias, 2 humeri, 2 calcanei, 1 radius). 85% identified as male and the median age was 53.9 years. Eighteen infections followed external fixation of fractures, with 4 cases after Ilizarov deformity correction, 2 cases followed ankle fusion and 3 after traction pin insertion. Fifteen patients were classified as BACH Uncomplicated and 12 were BACH Complex. The median follow-up was 3.99 years (2.00–8.05 years). Staphylococci were the most common pathogens (16 MSSA, 2 MRSA, 2 CNS). Polymicrobial infections were present in 5 cases (19%). All surgery was performed in a single stage following the same protocol at one institution. This included deep sampling, debridement, implantation of local antibiotics, culture-specific systemic antibiotics and soft tissue closure. Seven patients required flap coverage (6 local, 1 free flap), which was performed in the same operation. 25 (93%) patients had a successful outcome after one surgery. Two had recurrence of infection which was successfully treated by repeat of the protocol. One patient suffered a fracture through the operated site after a fall. This healed without infection recurrence. Wound leakage after local antibiotic treatment was seen in 3/27 (11%) of cases. All resolved without treatment. After a minimum of 2 years follow up, all patients were infection free at the site of the former osteomyelitis. Conclusions. OM after PSI is uncommon but has major implications for the patient as 7 out of 27 patients needed flap coverage. This reinforces the need for careful pin placement and pin site care to prevent deep infection. These infections require appropriate surgery, not just curettage. All patients in our cohort were infection-free after a minimum follow-up of 2 years suggesting that this protocol is effective

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

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

Aims. In our unit, we adopt a two-stage surgical reconstruction approach using internal fixation for the management of infected Charcot foot deformity. We evaluate our experience with this functional limb salvage method. Methods. We conducted a retrospective analysis of prospectively collected data of all patients with infected Charcot foot deformity who underwent two-stage reconstruction with internal fixation between July 2011 and November 2019, with a minimum of 12 months’ follow-up. Results. We identified 23 feet in 22 patients with a mean age of 56.7 years (33 to 70). The mean postoperative follow-up period was 44.7 months (14 to 99). Limb salvage was achieved in all patients. At one-year follow-up, all ulcers have healed and independent full weightbearing mobilization was achieved in all but one patient. Seven patients developed new mechanical skin breakdown; all went on to heal following further interventions. Fusion of the hindfoot was achieved in 15 of 18 feet (83.3%). Midfoot fusion was achieved in nine of 15 patients (60%) and six had stable and painless fibrous nonunion. Hardware failure occurred in five feet, all with broken dorsomedial locking plate. Six patients required further surgery, two underwent revision surgery for infected nonunion, two for removal of metalwork and exostectomy, and two for dynamization of the hindfoot nail. Conclusion. Two-stage reconstruction of the infected and deformed Charcot foot using internal fixation and following the principle of ‘long-segment, rigid and durable internal fixation, with optimal bone opposition and local antibiotic elusion’ is a good form of treatment provided a multidisciplinary care plan is delivered. Cite this article: Bone Joint J 2021;103-B(10):1611–1618

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

Periprosthetic joint infection (PJI) in geriatric and/or multimorbid patients is an enormous challenge for orthopaedic surgeons. Revision procedures have also been demonstrated to expose patients to higher infection risks. Prior patient stratification according to presumed infection risks, followed by a more potent local antibiotic prophylaxis protocol with selective use of DALBC, is an interesting strategy to decrease the burden of PJI in high risk patients. The PubMed & EMBASE databases were screened for publications pertaining to the utilization of DALBC in cement for infection prophylaxis & prosthesis fixation. 6 preclinical & 7 clinical studies were identified which met the inclusion criteria and were stratified by level of clinical evidence. Only those studies were considered which compared the PJI outcome in the DALBC vs the SALBC group. (1). DALBC have been shown to exert a much stronger and longer lasting inhibition of biofilm formation on many PJI relevant bacteria (gram-positive and gram-negative pathogens) than single gentamicin-only containing cements. (2). DALBC use (COPAL G+C) in the intervention arm of 7 clinical studies has led to a significant reduction of PJI cases in a) cemented hemiarthroplasty procedures (3 studies, evidence level I and III), in b) cemented septic revision surgeries (2 studies, evidence level III), in c) cemented aseptic knee revisions (1 study, evidence level III) and in d) cemented primary arthroplasties in multi-morbid patients (1 study, evidence level III-IV). These benefits were not associated with more systemic side effects or a higher prevalence of broad antimicrobial resistancies. Use of DALBC is likely to be more effective in preventing PJI in high risk patients. The preliminar findings so far may encourage clinicians to consolidate this hypothesis on a wider clinical range

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

Aim. To describe a 2-stage treatment pathway for managing neuropathic forefoot ulcers and the safety and efficacy of percutaneous tendo-Achilles lengthening (TAL) in out-patient clinics. Methods. Forefoot ulcers in patients with diabetic neuropathy are a result of factors that result in increased forefoot plantar pressure. Plantar flexed metatarsal heads secondary to progressive claw toe deformity and hindfoot equinus from changes within the gastrocnemius-soleus-tendo-Achilles complex, with additional contraction of tibialis posterior and peroneal longus, secondary to motor neuropathy results in progressive increase in forefoot plantar pressures. Consecutive patients, who presented to our Diabetic Foot clinic since February 2019 with forefoot ulcers or recurrent forefoot callosity were treated with TAL in the first instance, and in patients with recurrent or non-healing ulcers, by proximal dorsal closing wedge osteotomy; a 2-stage treatment pathway. Patients were followed up at 3, 6, and 12 months to assess ulcer healing and recurrence. Results. One hundred and twelve patients (146 feet) underwent TAL by 3 consultants in the out-patient clinics. Of these, 96 feet were followed for a minimum of 12 months (range 12–36 months). None had infection or wound related problems at the tenotomy sites; complete transection of the tendon was noted in 4 patients (4%) and one-patient developed heel callosity suggestive of over-lengthening. In 92 feet (96%), the ulcers healed within 10 weeks (± 4 weeks). Additional z-lengthening of peroneal longus and tibialis posterior tendons helped in patients with big-toe and 5. th. metatarsal head ulcers. In 12 feet (10%), the ulcer failed to heal or recurred, the MRI scan in these patients showed plantar flexed metatarsals secondary to progressive claw toe deformity. The ulcer in this group healed after surgical offloading with proximal dorsal closing wedge osteotomy. In patients with osteomyelitis, the intramedullary canal was curetted and filled with local antibiotic eluting agents such as Cerament G. ®. The osteotomy site was stabilised with a percutaneous 1.6mm k-wire. Conclusion. The described 2-stage treatment pathway results in long-term healing of neuropathic forefoot ulcers, and in 96% of patients, the ulcer healed after out-patient percutaneous TAL alone. TAL is a safe and effective initial out-patient procedure with improved patient outcomes

Aims. The microbiological detection of microorganisms plays a crucial role in the diagnosis as well as in the targeted systemic and local antibiotic therapy of periprosthetic infections (PJI). Despite extensive efforts to improve the sensitivity of current culture methods, the rate of culture-negative infections is approximately 10–20% of all PJI. This study investigates an preanalytical algorithm (culture collection and direct processing in the OR) to potentially increasing culture yield in patients with PJI. Methods. Patients undergoing staged revision arthroplasty for PJI in our hospital between October 2021 and 2022 were included in this prospective pilot study. Intraoperatively twenty tissue samples were collected and distributed among 4 groups. Tissue samples were prepared according to standard without medium and in thioglycolate medium at 3 different temperatures (room temperature, 4°C, 37° for 24h before transport to microbiology) directly in the OR. The removed implants were sonicated. Cultures were investigated on days 1, 3, 7, 12, 14 for possible growth. All grown organism, the number of positive samples and the time to positivity were recorded and compared. Results. 71 patients were included (age, gender). Compared to the standard procedure the thioglycolate broth at 37°C was significantly more often culture-negative (p=0.031). No significant differences in the frequency of culture-negative samples were detected in the other groups. 8.4% (6/71) patients were culture negative in the standard culture but positive in the thioglycolate samples. In contrast, 7% (5/71) were culture negative in the thioglycolate samples but had bacterial detection in the standard approach. In 4.7% (3/63) of the patients, only the sonication showed growth, whereas 25.4% (16/63) had no growth in sonication fluid but in one of the cultures. For S. caprae, there was a significantly different distribution (p=0.026) with more frequent detection in the group with thioglycolate at 37°C. The standard procedure (p=0.005) and sonication (p=0.023) showed a shorter time to positivity of the culture compared to the thioglycolate approach at 4°C. Conclusions. No general differences could be shown between the standard preparation and the thioglycolate preparation; in particular, storage at different temperatures does not seem to result in any difference. For individual cases (8% in this study), bacterial growth was detected in the thioglycolate group that would have been culture-negative otherwise. There might be organism dependent differences in growth in different media

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. infected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting. Patients and Method. We performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function. Results. We included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage. Conclusions. Masquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results

Aim. To describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis and answer the following research question; is the last debrided bone tissue viable and without signs of inflammation?. Method. In total, 15 patients with chronic osteomyelitis were allocated to surgical treatment using a one stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2), representing the status of the bone void. In all cases, the surgeon debrided the bone until visual confirmation of healthy bleeding bone. The samples were processed for histology, i.e. decalcification and paraffin embedding, followed by cutting and staining with Haematoxylin and Eosin. Immunohistochemistry with MAC-387 antibodies towards the calprotectin of neutrophil granulocytes (NGs) was also performed and used for estimation of a neutrophil granulocyte (NG) score (0, 1, 2 or 3), by the method described for fracture related infections (1). Results. For the S1 samples the median NG score was 3 which is considered confirmatory for infection. However, following debridement the median NG score was significantly (p = 0.032) reduced to 2. Often NGs were seen as single cells, but in seven S1 samples and in one S2 sample massive NG accumulations were observed. The S1 samples showed a mix of granulation tissue, fibrosis, viable bone, and bone necrosis. The S2 samples contained viable bone tissue and occasionally (10/15) small fragments of necrotic bone or bone debris were seen. Furthermore, a large number of erythrocytes were observed in most S2 samples. Conclusions. The present study shows that the inflammatory response still existents after debridement, although the response fades from the center of infection. Therefore, sampling of debrided bone tissue for histology must be performed initially during surgery, to avoid underestimation of the inflammatory response, i.e. the NG score. The last debrided bone tissue cannot by definition be considered completely viable and caution should be made to remove blood (rinse) before intraoperative evaluation of the viability of debrided cancellous bone. Remnant necrotic bone fragments or debris could represent low-vascular hiding places for leftover bacteria. Application of local antibiotics might have a central role in clearing of these small non-viable bone pieces at the bone void interface

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

Introduction. Treatment of non-union in open tibial fractures Gustilo-Anderson(GA)-3A/3B fractures remains a challenging problem. Most of these can be dealt using treatment methods that requires excision of the non-union followed by bone grafting, masquelet technique, or acute shortening. Circular fixators with closed distraction or bone transport also remains a useful option. However, sometimes due to patient specific factors these cannot be used. Recently antibiotic loaded bone substitutes have been increasingly used for repairing infected non-unions. They provide local antibiotic delivery, fill dead space, and act as a bone conductive implant, which is resorted at the end of a few months. We aimed to assess the outcome of percutaneous injection of bone substitute while treating non-union of complex open tibial fractures. Materials & Methods. Three cases of clinical and radiological stiff tibial non-union requiring further intervention were identified from our major trauma open fracture database. Two GA-3B cases, treated with a circular frame developed fracture-related-infection(FRI) manifesting as local cellulitis, loosened infected wires/pins with raised blood-markers, and one case of GA-3A treated with an intramedullary nail. At the time of removal of metalwork/frame, informed consent was obtained and Cerament-G. TM. (bone-substitute with gentamicin) was percutaneously injected through a small cortical window using a bone biopsy(Jamshedi needle). All patients were allowed to weight bear as tolerated in a well-fitting air-cast boot and using crutches. They were followed up at 6 weekly intervals with clinical assessment of their symptoms and radiographs. Fracture union was assessed using serial radiographs with healing defined as filling of fracture gap, bridging callus and clinical assessment including return to full painless weight bearing. Results. Follow-up at 6 months showed all fractures had healed with no defect or gaps with evidence of new trabecular bone and significant resorption of Cerament-G. TM. at final follow-up. There was no evidence of residual infection with restoration of normal limb function. Fractures with no internal fixation showed a mild deformity that had developed during the course of the healing, presumed due to mild collapse in the absence of fixation. These were less than 10 degrees in sagittal and coronal planes and were clinically felt to be insignificant by the patients. Conclusions. Cerament-G's unique combination of high dose antibiotics and hydroxy apatite matrix provided by calcium sulphate might help provide an osteoconductive environment to allow these stiff non-unions to heal. The matrix appears to provide a scaffold-like structure that allows new bone in-growth with local release of antibiotics helping reduce deep-seated infections. The final deformation at fracture site underlines the need for fixation- and it is very unlikely that this technique will work in mobile nonunions. Whilst similar fractures may heal without the use of bone substitute injections, the speed of healing in presence of significant fracture gap suggests the use of these bone substitutes did help in our cases. Further studies with a larger cohort, including RCTs, to evaluate the effectiveness of this technique compared to other methods are needed

Aim. The use of bone substitutes such as calcium sulfate (CaSO4) and hydroxyapatite with local antibiotics are crucial in the treatment of osteomyelitis. They allow the treatment of the dead space and locally provide large concentrations of antibiotics. However, it is unknown whether use of local vancomycin may elute and influence on vancomycin plasma levels. The aim of this study is to assess whether the addition of vancomycin to CaSO4 with hydroxyapatite may increase vancomycin plasma concentrations in in patients with osteomyelitis and therefore alter dosage adjustments. Method. The present study investigates the vancomycin plasma concentrations at 72–94 h post-surgery after the application of local vancomycin within CaSO4 (660mg vancomycin/10cc) and hydroxyapatite bone substitute in patients treated with empiric intravenous vancomycin and surgically treated for osteomyelitis. Vancomycin plasma concentrations were analyzed in twelve patients with osteomyelitis surgically treated with local release of vancomycin by CaSO4 and hydroxyapatite and undergoing therapeutic drug monitoring (TDM) of their vancomycin plasma concentrations as it is routinely done in our hospital. From 2019 to 2022, demographic data, microbiology, type of osteomyelitis, amount of local vancomycin applied, alteration of renal function, and vancomycin levels were retrospectively analyzed. Results. Twelve patients were included: 9(75%) were men. Median (range) demographic and clinical data: age: 51(26–67) years; body mass index: 27.7(18–46.4) kg/m2;baseline serum creatinine: 0.85 (0.7–1.24)mg/dl and 5(41.7%) with and glomerular filtration rate < 90ml/min(CPD-EPI, ml/min). Most frequently isolated microorganisms were Staphylococci (58%). Seven (54%) patients were classified as Cierny-Mader Osteomyelitis type III, 3(23%) as type IV and 2(23%) as type I. Treatment data: initial dose of vancomycin: 1g/8h in 9(75.0%) and 1g/12h in 3(25%) patients, total daily dose/body weight: 35.3(15.9–46.2) mg/kg. Pharmacokinetic data:days of iv vancomycin treatment until first TDM measurement: 3(3–4) days; minimum and maximum vancomycin plasma concentrations: 9.4(3–17.3) mg/L and 19.6(11.3–33.4) mg/L, respectively; patients with therapeutic concentrations: 6(50%); infratherapeutic: 4(33.3%) and supratherapeutic/potentially toxic: 2(16.7%). These 2 patients were young, had a baseline conserved renal function and were receiving the higher dose of 1g/8h. Conclusions. Vancomycin incorporated into the bone substitute appears not to increase blood concentrations of the glycopeptide in patients with osteomyelitis treated surgically and with intravenous vancomycin. However, 2 of the 12 patients presented supratherapeutic and potentially nephrotoxic vancomycin concentrations in the first TDM measurement, even though they were young and without renal impairment and needed and unexpected dose reduction. These results suggest the need to confirm the safety of local vancomycin in further larger clinical studies

Orthopedic device-related bone infection is one of the most distressing complications of the surgical fixation of fractures. Despite best practice in medical and surgical interventions, the rate of infection remains stubbornly persistent, and current estimates indicate that treatment failure rates are also significant. As we approach the limit of the effectiveness of current anti-infective preventative and therapeutic strategies, novel approaches to infection management assume great importance. This presentation will describe our efforts to develop and test various hydrogels to serve as customized antibiotic delivery vehicles for infection prevention and treatment. Hydrogels offer solutions for many of the challenges faced by complex trauma wounds as they are not restricted spatially within a poorly defined surgical field, they often degrade rapidly with no compatibility issues, and releases 100% of the loaded antibiotic. The preliminary data set proving efficacy in preventing and treating infection in both rabbit and sheep studies will be described, including local antibiotic concentrations in the intramedullary canal over time, compared to that of the more conventional antibiotic loaded bone cement. These two technologies show potential for the prevention and treatment of infection in trauma patients, with a clear focus on optimized antibiotic delivery tailored for complex wounds

The duration of systemic antibiotics following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, high concentration of 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 for two-stage hip revision. A retrospective review of our Institution's prospective database was performed to identify all intended two-stage hip revision procedures for PJI. All patients had a confirmed PJI as per MSIS 2013 criteria, minimum 5-years follow up and outcomes according to the MSIS working group outcome-reporting tool; then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year). 383 intended two-stage hip revisions were identified; of which 299 met our inclusion criteria, in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage). Median follow up was 10.7 years (IQR 6.3 – 15.0). 258 (86%) patients proceeded to 2. nd. stage surgery. 91% success rate was observed for those patients who underwent reimplantation, although dropping to 86% when including the patients who did not proceed to second stage. The median duration of post-operative systemic antibiotics was 5 days (IQR 5–9). No significant difference 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 with two-stage exchange or gram-positive PJI (86%); than for gram-negative PJI (81%) and polymicrobial infection (74%) (p=0.36). Fungal PJI was observed to have a significantly reduced rate of success (n=3; 33%; p=0.03). Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage to manage PJI of the hip provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs

Infection is still a major problem in implant surgery. Most infections are caused by bacteria that enter the wound at the time of the operation. Although prophylactic antibiotics given intravenously have been shown to be effective if given during the correct time frame, the concentration of local antibiotics in the knee in response to intravenous antibiotics is about 1/3 that achieved in the serum, and the level is transient. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and cost analysis shows a remarkable monetary benefit to this effect. Local antibiotic irrigation during implant surgery is inexpensive, easy, and effective