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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 44 - 44
1 Oct 2022
Young B Dudareva M Vicentine M Hotchen A McNally M
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 76 - 76
1 Dec 2022
Kruse C Axelrod D Johal H Al-Mohrej O Daniel R
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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


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 84 - 84
22 Nov 2024
Unsworth A McNally M Scarborough M Young B
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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


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 89 - 89
1 Dec 2018
Morgenstern M Vallejo A McNally M Moriarty F Ferguson J Nijs S Metsemakers W
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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


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_1 | Pages 88 - 88
1 Feb 2015
Whiteside L
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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


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_12 | Pages 49 - 49
1 Jul 2014
Whiteside L
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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


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 60 - 60
1 Dec 2015
Agarwal S Hughes H
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_6 | Pages 10 - 10
1 May 2021
Aljawadi A Islam A Jahangir N Niazi N Ferguson Z Sephton B Elmajee M Reid A Wong J Pillai A
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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%


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 46 - 46
1 Dec 2018
Ferguson J Mifsud M Stubbs D McNally M
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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


The Bone & Joint Journal
Vol. 98-B, Issue 1_Supple_A | Pages 23 - 26
1 Jan 2016
Whiteside LA

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.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 44 - 44
24 Nov 2023
Bruyninckx S Vles G
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Aim

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

Method

A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 113 - 113
1 Dec 2013
Kwon OS Lee JH Oh SH
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 207 - 207
1 Sep 2012
Leung A Hawthorn B Simpson A
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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.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

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


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 71 - 71
1 Dec 2019
Denes E Fiorenza F Toullec E Bertin F Balkhi SE
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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.

Method

Two patients had a destroyed sternum following mediastinitis; one presented a femoral chronic osteomyelitis due to MRSA and one had an infected ankle arthroplasty. The ceramic was loaded with gentamicin in three cases and vancomycin for the ankle infection. Local dosages thanks to Redon's drain and blood samples were performed. Loading was done to protect the device while implanted in an infected area and was combined with conventional antibiotic therapy.


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1537 - 1544
1 Nov 2017
Wahl P Guidi M Benninger E Rönn K Gautier E Buclin T Magnin J Livio F

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.

Patients and Methods

A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 4 - 4
22 Nov 2024
Pidgaiska O Goumenos S Dos Santos MV Trampuz A Stöckle U Meller S
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Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 84 - 84
1 Oct 2022
Sliepen J Corrigan R Dudareva M Wouthuyzen-Bakker M Rentenaar R Atkins B Hietbrink F Govaert G McNally M Ijpma F
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 11 - 11
1 Dec 2021
Corrigan R Sliepen J Rentenaar R Hietbrink F IJpma F Atkins B Govaert G McNally M Wouthuyzen-Bakker M
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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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_10 | Pages 9 - 9
1 Jun 2023
Kapoor D Condell R Kennedy N Bakhshayesh P
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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