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

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

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

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

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