Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517

Aims. The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183–188

Aims. Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. Methods. A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Results. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months (24 to 133). The seven-year infection-free survival was 87.6% (95% confidence interval (CI) 79.4 to 95.8). No significant difference in infection-free survival was observed between hip and knee PJIs (91.5% (95% CI 79.9 to 100) vs 84.7% (95% CI 73.1 to 96.3); p = 0.648). The mean postoperative Harris Hip Score was 76.1 points (63.2 to 92.4) and Hospital for Special Surgery score was 78. 2 (63.2 to 92.4) at the most recent assessment. Polymicrobial and fungal infections accounted for 14.1% (11/78) and 9.0% (7/78) of all cases, respectively. Conclusion. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid, thereby overcoming reduced vascular supply and biofilm formation. This supplementary route of administration may be a viable option in treating PJI after multiple failed prior surgeries for reinfection. Cite this article: Bone Joint J 2022;104-B(7):867–874

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding. Cite this article: Bone Joint J 2023;105-B(8):850–856

Aims. The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown. Methods. A review of all revision TKAs which were undertaken between 2006 and 2018 in a tertiary referral centre was performed, including all those meeting the consensus criteria for PJI, in which organisms were identified. Using a cluster analysis, three chronological time periods were created. We then evaluated the antibiotic resistance of the identified bacteria between these three clusters and the effectiveness of our antibiotic regime. Results. We identified 129 PJIs with 161 culture identified bacteria in 97 patients. Coagulase-negative staphylococci (CNS) were identified in 46.6% cultures, followed by Staphylococcus aureus in 19.8%. The overall resistance to antibiotics did not increase significantly during the study period (p = 0.454). However, CNS resistance to teicoplanin (p < 0.001), fosfomycin (p = 0.016), and tetracycline (p = 0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and was the most effective agent. Conclusion. Although we were unable to show an overall increase in antibiotic resistance in organisms that cause PJI after TKA during the study period, this was not true for CNS. It is concerning that resistance of CNS to new antibiotics, but not vancomycin, has increased in a little more than a decade. Our findings suggest that referral centres should continuously monitor their bacteriological analyses, as these have significant implications for prophylactic treatment in both primary arthroplasty and revision arthroplasty for PJI. Cite this article: Bone Joint J 2021;103-B(6 Supple A):171–176

We present a series of 114 patients with microbiologically-proven chronically-infected total hip replacement, treated between 1991 and 2004 by a two-stage exchange procedure with antibiotic-loaded cement, but without the use of a prolonged course of antibiotic therapy. The mean follow-up for all patients was 74 months (2 to 175) with all surviving patients having a minimum follow-up of two years. Infection was successfully eradicated in 100 patients (87.7%), a rate which is similar to that reported by others, but where prolonged adjuvant antibiotic therapy has been used. Using the technique described, a prolonged course of systemic antibiotics does not appear to be essential and the high cost of the administration of antibiotics can be avoided

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190

Aims. In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI. Methods. A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups. Results. Of 51 CN patients, 46 (90.2%) required no additional medical treatment for recurrent infection at a mean of 53.2 months (24 to 72) of follow-up. Impaired kidney function occurred in two patients, and one patient had a local skin rash. No significant difference in the infection control rate was observed between CN and CP PJIs (90.2% (46/51) versus 94.3% (181/192); p = 0.297). The HHS of the CN group showed no substantial difference from that of CP cases (79 versus 81; p = 0.359). However, the CN group showed a mean HSS inferior to that of the CP group (76 versus 80; p = 0.027). Conclusion. Single-stage revision with direct intra-articular antibiotic infusion can be effective in treating CN PJI, and can achieve an infection control rate similar to that in CP patients. However, in view of systemic toxicity, local adverse reactions, and higher costs, additional strong evidence is needed to verify these treatment regimens. Cite this article: Bone Joint J 2020;102-B(3):336–344

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date. Cite this article: Bone Joint J 2023;105-B(11):1135–1139

Prophylactic antibiotics can decrease the risk of wound infection and have been routinely employed in orthopaedic surgery for decades. Despite their widespread use, questions still surround the selection of antibiotics for prophylaxis, timing and duration of administration. The health economic costs associated with wound infections are significant, and the judicious but appropriate use of antibiotics can reduce this risk. This review examines the evidence behind commonly debated topics in antibiotic prophylaxis and highlights the uses and advantages of some commonly used antibiotics. Cite this article: Bone Joint J 2016;98-B:1014–19

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

Aims. The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure. Patients and Methods. This was a single-centre retrospective review of 134 infected primary TKAs that were treated with IDCR. Infections within four weeks of the procedure were defined as acute postoperative infections, and those occurring more than four weeks after the procedure with symptoms for less than three weeks were defined as acute haematogenous infections. Patients were treated with intravenous antibiotics for four to six weeks, followed by chronic oral antibiotic suppression. Estimates of survival were made using a competing risk analysis. The mean follow-up was five years (2.1 to 13). Results. The infection was an acute postoperative infection in 23 TKAs and an acute haematogenous infection in 111 TKAs. The incidence of subsequent infection was 36% in those with an acute postoperative infection and 33% in those with a haematogenous infection, five years postoperatively (p = 0.40). Age < 60 years increased the risk of subsequent infection (hazard ratio (HR) 2.4; p = 0.009) and removal of the components (HR 2.8; p = 0.007). Infection with a staphylococcal species increased the risk of subsequent infection (HR 3.6; p < 0.001), and removal of the components (HR 3.2; p = 0.002). Musculoskeletal Infection Society host type and local extremity grade, body mass index (BMI), the duration of symptoms, gender, and the presence of a monoblock tibial component had no significant effect on the outcome. Conclusion. In a rigorously defined group of acute periprosthetic infections after TKA treated with IDCR and chronic antibiotic suppression, the infection-free survival at five years was 66%. The greatest risk factor for failure was an infection with a staphylococcal species, followed by age of < 60 years. Cite this article: Bone Joint J 2018;100-B:1471–76

Aims. Debridement, antibiotics, and implant retention (DAIR) is a widely accepted form of surgical treatment for patients with an early periprosthetic joint infection (PJI) after primary arthroplasty. The outcome of DAIR after revision arthroplasty, however, has not been reported. The aim of this study was to report the success rate of DAIR after revision arthroplasty with a follow-up of two years. Methods. This retrospective study, conducted at the Sint Maartenskliniek, Nijmegen, the Netherlands, included 88 patients who underwent DAIR within 90 days of revision total hip or total knee arthroplasty between 2012 and 2019. Details of the surgical procedures and PJI were collected. Univariate analysis and a subgroup analysis of the culture-positive group were performed. Kaplan-Meier survivorship curves were constructed. Results. The overall success rate of DAIR, with respect to the retention of components and the cure of infection, was 68% after two years. DAIR performed with an interval of > 30 days after the index revision procedure (odds ratio (OR) 0.24 (95% confidence interval (CI) 0.08 to 0.72); p = 0.008), a repeated DAIR within 90 days (OR 0.37 (95% CI 0.14 to 0.97); p = 0.040), and the use of an immunosuppressive agent (OR 0.13 (95% CI 0.02 to 0.67); p = 0.012) were associated with a significantly reduced success rate. In the culture-positive group, a mismatch between the antibiotic treatment and the susceptibility of the organism was associated with a significantly lower success rate (OR 0.13 (95% CI 0.03 to 0.62); p = 0.007). Conclusion. DAIR is an acceptable form of surgical treatment for patients with a suspected early PJI after revision arthroplasty of the hip or knee. DAIRs performed after a prolonged interval, multiple DAIRs, and antibiotic mismatches were significantly associated with an increased risk of failure. Optimization of the host immune response and the prevention of antibiotic mismatch are modifiable factors that may improve the outcome. The high rate of mismatches was an important finding, underlining the need for a review of the local microbiological data, which might improve the outcome. Cite this article: Bone Joint J 2022;104-B(4):464–471

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

Aims. The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. Patients and Methods. We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. Results. Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. Conclusion. PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9–15

Aims. The Open-Fracture Patient Evaluation Nationwide (OPEN) study was performed to provide clarity in open fracture management previously skewed by small, specialist centre studies and large, unfocused registry investigations. We report the current management metrics of open fractures across the UK. Method. Patients admitted to hospital with an open fracture (excluding phalanges or isolated hand injuries) between 1 June 2021 and 30 September 2021 were included. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture software. All domains of the British Orthopaedic Association Standard for Open Fracture Management were recorded. Results. Across 51 centres, 1,175 patients were analyzed. Antibiotics were given to 754 (69.0%) in the emergency department, 240 (22.0%) pre-hospital, and 99 (9.1%) as inpatients. Wounds were photographed in 848 (72.7%) cases. Median time to first surgery was 16 hrs 14 mins (interquartile range (IQR) 8 hrs 29 mins to 23 hrs 19 mins). Complex injuries were operated on sooner (median 12 hrs 51 mins (IQR 4 hrs 36 mins to 21 hrs 14 mins)). Of initial procedures, 1,053 (90.3%) occurred between 8am and 8pm. A consultant orthopaedic surgeon was present at 1,039 (89.2%) first procedures. In orthoplastic centres, a consultant plastic surgeon was present at 465 (45.1%) first procedures. Overall, 706 (60.8%) patients required a single operation. At primary debridement, 798 (65.0%) fractures were definitively fixed, while 734 (59.8%) fractures had fixation and coverage in one operation through direct closure or soft-tissue coverage. Negative pressure wound therapy was used in 235 (67.7%) staged procedures. Following wound closure or soft-tissue cover, 509 (47.0%) patients received antibiotics for a median of three days (IQR 1 to 7). Conclusion. OPEN provides an insight into care across the UK and different levels of hospital for open fractures. Patients are predominantly operated on promptly, in working hours, and at specialist centres. Areas for improvement include combined patient review and follow-up, scheduled operating, earlier definitive soft-tissue cover, and more robust antibiotic husbandry. Cite this article: Bone Joint J 2022;104-B(9):1073–1080

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

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

We used a goat model of a contaminated musculoskeletal defect to determine the effectiveness of rapidly-resorbing calcium-sulphate pellets containing amikacin to reduce the local bacterial count. Our findings showed that this treatment eradicated the bacteria quickly, performed as well as standard polymethylmethacrylate mixed with an antibiotic and had many advantages over the latter. The pellets were prepared before surgery and absorbed completely. They released all of the antibiotic and did not require a subsequent operation for their removal. Our study indicated that locally administered antibiotics reduced bacteria within the wound rapidly. This method of treatment may have an important role in decreasing the rate of infection in contaminated wounds

We reviewed systematically the published evidence on the effectiveness of antibiotic prophylaxis for the reduction of wound infection in patients undergoing total hip and total knee replacement. Publications were identified using the Cochrane Library, MEDLINE, EMBASE and CINAHL databases. We also contacted authors to identify unpublished trials. We included randomised controlled trials which compared any prophylaxis with none, the administration of systemic antibiotics with that of those in cement, cephalosporins with glycopeptides, cephalosporins with penicillin-derivatives, and second-generation with first-generation cephalosporins. A total of 26 studies (11 343 participants) met the inclusion criteria. Methodological quality was variable. In a meta-analysis of seven studies (3065 participants) antibiotic prophylaxis reduced the absolute risk of wound infection by 8% and the relative risk by 81% compared with no prophylaxis (p < 0.00001). No other comparison showed a significant difference in clinical effect. Antibiotic prophylaxis should be routine in joint replacement but the choice of agent should be made on the basis of cost and local availability

Aims. The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods. A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results. Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion. This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9

Aims. This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods. A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results. Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion. We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations. Cite this article: Bone Joint J 2024;106-B(7):720–727

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

We have assessed the effect of different regimes of antibiotic prophylaxis on the survival of total hip implants, comparing antibiotics administered both systemically and in the bone cement, systemically only, in the bone cement only and with no antibiotics given. We studied 10 905 primary cemented total hip replacements, performed for osteoarthritis of the hip and reported to the Norwegian arthroplasty register between 1987 and 1995. Cox-estimated failure-rate ratios (FRR) are presented with adjustment for gender, age, the brand of cement, the prosthesis, the type of operating theatre and the operating time. For revisions performed for infection (39 operations), the lowest rate of revision was found among patients receiving antibiotic-containing cement plus systemic antibiotics (n = 5804). The revision rate for the 4586 patients receiving systemic antibiotics only was 4.3 times greater (95% CI 1.7 to 11.0, p = 0.001); in 239 with antibiotics in the bone cement only it was 6.3 times greater (CI 1.6 to 25.0, p = 0.003); and in the 276 who did not receive antibiotics it was by 11.5 times greater (CI 2.1 to 63.0, p = 0.002). Adjustment for the total amount of systemic antibiotic administered did not change the results. We also observed an increased revision rate for aseptic loosening (109 operations) comparing the systemic-only (FRR = 1.8, CI 1.1 to 2.9, p = 0.01) and the cement-only regimes (FRR = 2.6, CI 1.2 to 5.9, p = 0.02) with the combined dosage. Our findings show that systemic antibiotics combined with antibiotic-containing bone cement led to fewer revisions than the other methods

Aims. Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

The release of various penicillins and other antibiotics from two brands of polymerised bone cement has been studied in vitro and in vivo in mice. Bone cement plugs containing antibiotics demonstrated antibacterial activity as a result of diffusion of antibiotic from the plugs into the surrounding medium. With all antibiotics tested, from 2-5 to 10 per cent of the antibiotic in the cement was released in vitro in active form within twenty-four hours. Most of the activity appeared within three hours of the start of the test, but in some cases low levels of activity were detected after four days. Antibiotic cement plugs implanted in mice and rats produced low concentrations of antibiotic in the blood up to two hours after implantation, but activity was seldom detected subsequently. In general, penicillins and non-penicillin antibiotics showed similar diffusion characteristics, and the pattern of release in vitro and in vivo was consistent with the leaching of antibiotic from, or near, the surface of the bone cement

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity. This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment. We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis. No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro

Iontophoresis is a novel technique which may be used to facilitate the movement of antibiotics into the substance of bone using an electrical potential applied externally. We have examined the rate of early infection in allografts following application of this technique in clinical practice. A total of 31 patients undergoing revision arthroplasty or surgery for limb salvage received 34 iontophoresed sequential allografts, of which 26 survived for a minimum of two years. The mean serum antibiotic levels after operation were low (gentamicin 0.37 mg/l (0.2 to 0.5); flucloxacillin 1 mg/l (0 to 1) and the levels in the drains were high (gentamicin 40 mg/l (2.5 to 131); flucloxacillin 17 mg/l (1 to 43). There were no early deep infections. Two late infections were presumed to be haemotogenous; 28 of the 34 allografts were retained. In 12 patients with pre-existing proven infection further infection has not occurred at a mean follow-up of 51 months (24 to 82)

All major studies have incorporated the use of prolonged courses of parenteral or oral antibiotic therapy in the management of two-stage revision of an infected total knee arthroplasty. We present a series of 59 consecutive patients, all with microbiologically-proven deep infection of a total knee arthroplasty, in whom a prolonged course of antibiotic therapy was not routinely used. The mean follow-up was 56.4 months (24 to 114). Of the 38 patients who underwent a staged exchange, infection was successfully eradicated in 34 (89%) but recurrent or persistent infection was present in four (11%). Our rate of cure for infection is similar to that reported elsewhere. We conclude that a prolonged course of antibiotic therapy seems not to alter the incidence of recurrent or persistent infection. The costs of the administration of antibiotics are high and such a regime may be unnecessary

Aims. To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis. Patients and Methods. Bone samples from the femoral head, neck and acetabulum were collected from 18 patients undergoing total hip arthroplasty (THA) and from the femur and tibia in 21 patients during total knee arthroplasty (TKA). The concentration of both antibiotics in the samples was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured against both the minimum inhibitory concentration 50, and the more stringent epidemiological cutoff value for resistance (ECOFF). Results. The bone penetration of gentamicin was higher than flucloxacillin. Relative to ECOFF, flucloxacillin concentrations were effective against S. aureus and S. epidermidis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S. epidermidis in all bone samples. Gentamicin was effective against S. aureus in 11 (61.1%) femoral neck samples in THA. Effective concentrations of gentamicin against S. aureus were only achieved in four (19%) femoral and six (29%) tibial samples in TKA. Conclusion. Flucloxacillin and gentamicin were found to penetrate bone during THA and TKA. Gentamicin was effective against S. epidermidis in both THA and TKA, while levels were subtherapeutic against S. aureus in most TKAs. Bone penetration of both antibiotics was less in TKA than THA, and may relate to the use of a tourniquet. Using this antibiotic combination, effective cover against the two common infective organisms was achieved in all THAs and all but one TKA. Cite this article: Bone Joint J 2017;99-B:358–64

The role of antibiotics in the treatment of disc-space infection is controversial. This study assessed the tissue penetration of flucloxacillin and cephradine into the normal intervertebral disc after intravenous administration of a bolus dose of antibiotic. Twenty-five discs were removed from 12 adolescent patients having anterior spinal surgery to correct scoliosis; antibiotic had been administered between 30 minutes and four hours before operation. Despite high blood levels, no antibiotic could be detected by bioassay or by high-pressure liquid chromatography (h.p.l.c.) in any of the specimens from the nucleus pulposus or the annulus fibrosus

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

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Intramedullary infection in long bones represents a complex clinical challenge, with an increasing incidence due to the increasing use of intramedullary fixation. We report a prospective case series using an intramedullary reaming device, the Reamer–Irrigator–Aspirator (RIA) system, in association with antibiotic cement rods for the treatment of lower limb long bone infections. A total of 24 such patients, 16 men and eight women, with a mean age of 44.5 years (17 to 75), 14 with femoral and 10 with tibial infection, were treated in a staged manner over a period of 2.5 years in a single referral centre. Of these, 21 patients had had previous surgery, usually for fixation of a fracture (seven had sustained an open fracture originally and one had undergone fasciotomies). According to the Cierny–Mader classification system, 18 patients were classified as type 1A, four as 3A (discharging sinus tract), one as type 4A and one as type 1B. Staphylococcus species were isolated in 20 patients (83.3%). Local antibiotic delivery was used in the form of impregnated cement rods in 23 patients. These were removed at a mean of 2.6 months (1 to 5). Pathogen-specific antibiotics were administered systemically for a mean of six weeks (3 to 18). At a mean follow-up of 21 months (8 to 36), 23 patients (96%) had no evidence of recurrent infection. One underwent a planned trans-tibial amputation two weeks post-operatively due to peripheral vascular disease and chronic recalcitrant osteomyelitis of the tibia and foot. The combination of RIA reaming, the administration of systemic pathogen-specific antibiotics and local delivery using impregnated cement rods proved to be a safe and efficient form of treatment in these patients. Cite this article: Bone Joint J 2014; 96-B:783–8

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics. These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively). Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis. Cite this article: Bone Joint J 2013;95-B:831–7

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake

When using a staged approach to eradicate chronic infection after total hip replacement, systemic delivery of antibiotics after the first stage is often employed for an extended period of typically six weeks together with the use of an in situ antibiotic-eluting polymethylmethacrylate interval spacer. We report our multi-surgeon experience of 43 consecutive patients (44 hips) who received systemic vancomycin for two weeks in combination with a vancomycin- and gentamicin-eluting spacer system in the course of a two-stage revision procedure for deep infection with a median follow-up of 49 months (25 to 83). The antibiotic-eluting articulating spacers fractured in six hips (13.9%) and dislocated in five patients (11.6%). Successful elimination of the infecting organisms occurred in 38 (92.7%) of 41 hips with three patients developing superinfection with a new organism. We conclude that prolonged systemic antibiotic therapy may not be essential in the two-stage treatment of a total hip replacement for Gram-positive infection, provided that a high concentration of antibiotics is delivered locally using an antibiotic-eluting system

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores

A randomised prospective trial was undertaken of antibiotic prophylaxis given at various intervals before inflation of the tourniquet for arthroplasty of the knee. Cefuroxime assays of bone and subcutaneous fat from samples collected throughout the operation demonstrated that an interval of 10 minutes was necessary to obtain adequate prophylaxis. Improvement in the timing of antibiotic prophylaxis may result in a reduction in the incidence of infection

Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO. 2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin

We report two cases of epicondylitis of the elbow occurring after treatment with fluoroquinolone antibiotics. Both patients had intense pain which appeared very shortly after the first dose of the drug and was not relieved by conservative treatment. Ultrasonography revealed extensive inflammatory lesions with pseudonecrotic areas. MRI confirmed the lesions and also showed a subclinical abnormality of the adjoining tendons. The persistent nature of the pain was the indication for surgical release of the extensor mechanism. After operation pain disappeared completely and the patients were able to return to their normal activities. Lesions of the tendo Achillis are a well-known side-effect of treatment with fluoroquinolone. Our two cases show that such lesions may occur elsewhere. They also indicate the need for caution when prescribing these antibiotics to patients at risk of tendon lesions, such as top-level sportsmen or patients on dialysis or steroid treatment

Antibiotic impregnated articulating spacers are used in two-stage revision total knee arthroplasty to deliver local antibiotic therapy while preserving function. We have observed infection control in greater than 95% of cases with functional outcomes approaching those seen in revision for aseptic loosening. Higher failure has been observed with methicillin resistant organisms.

Two-stage revision surgery for infected total knee replacement offers the highest rate of success for the elimination of infection. The use of articulating antibiotic-laden cement spacers during the first stage to eradicate infection also allows protection of the soft tissues against excessive scarring and stiffness. We have investigated the effect of cyclical loading of cement spacers on the elution of antibiotics. Femoral and tibial spacers containing vancomycin at a constant concentration and tobramycin of varying concentrations were studied in vitro. The specimens were immersed and loaded cyclically to 250 N, with a flexion excursion of 45°, for 35 000 cycles. The buffered solution was sampled at set intervals and the antibiotic concentration was established so that the elution could be calculated. Unloaded samples were used as a control group for statistical comparison. The elution of tobramycin increased proportionately with its concentration in cement and was significantly higher at all sampling times from five minutes to 1680 minutes in loaded components compared with the control group (p = 0.021 and p = 0.003, respectively). A similar trend was observed with elution of vancomycin, but this failed to reach statistical significance at five, 1320 and 1560 minutes (p = 0.0508, p = 0.067 and p = 0.347, respectively). However, cyclically loaded and control components showed an increased elution of vancomycin with increasing tobramycin concentration in the specimens, despite all components having the same vancomycin concentration. The concentration of tobramycin influences both tobramycin and vancomycin elution from bone cement. Cyclical loading of the cement spacers enhanced the elution of vancomycin and tobramycin

We have investigated the contaminating bacteria in primary hip arthroplasty and their sensitivity to the prophylactic antibiotics currently in use. Impressions (627) of the gloved hands of the surgical team in 50 total hip arthroplasties were obtained on blood agar. The gloves were changed after draping, at intervals of 20 minutes thereafter, and before using cement. Changes were also undertaken whenever a visible puncture was detected. The culture plates were incubated at 37°C for 48 hours. Isolates were identified and tested for sensitivity to flucloxacillin, which is a recognised indicator of sensitivity to cefuroxime. They were also tested against other agents depending upon their appearance on Gram staining. We found contamination in 57 (9%) impressions and 106 bacterial isolates. Coagulase-negative staphylococci were seen most frequently (68.9%), but we also isolated Micrococcus (12.3%), diphtheroids (9.4%), Staphylococcus aureus (6.6%) and Escherichia coli (0.9%). Of the coagulase-negative staphylococci, only 52.1% were sensitive to flucloxacillin and therefore to cefuroxime. We believe that it is now appropriate to review the relevance of prophylaxis with cefuroxime and to consider the use of other agents

Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation. Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release. A 'tourniquet-release' dose of antibiotic increased drain fluid concentration threefold

The diffusion of Fucidin, gentamicin, and clindamycin from acrylic cement was tested in an in vitro system. The activity of Fucidin was very short-lived and only against gram-positive organisms; gentamicin inhibited gram-positive and gram-negative organisms for twenty-two and eleven days respectively; clindamycin had significant action only against gram-positive organisms and retained some activity for fifty-six days. We suggest that the destruction of organisms in the tissues is more likely to be achieved by topical and intravenous administration of antibiotics during the operation than by incorporation of antibiotic in the cement

Discitis after discography is due to bacterial penetration into the intervertebral disc by a contaminated needle and has an incidence of 1% to 4%. We have examined the prophylactic role of cephazolin administered at the time of discography. An experimental study in sheep using radiographic contrast containing Staphylococcus epidermidis showed that either adding the antibiotic to the intradiscal suspension or giving it intravenously 30 minutes before intradiscal inoculation of bacteria prevented any radiographic, macroscopic or histological signs of discitis; all the intervertebral disc cultures were negative. In a prospective clinical study of 127 consecutive patients having lumbar discography, the injected contrast contained cephazolin 1 mg per ml. None of the patients developed clinical or radiographic signs of discitis. We recommend the use of a suitable broad spectrum antibiotic in a single prophylactic dose whenever the intervertebral disc is entered

We present a series of 48 patients with infected total knee replacements managed by the use of articulating cement spacers and short-term parenteral antibiotic therapy in the postoperative period. All patients had microbiological and/or histological confirmation of infection at the first stage of their revision. They all underwent re-implantation and had a mean follow-up of 48.5 months (26 to 85). Infection was successfully eradicated in 42 of the 48 patients (88%). Six had persistent infection which led to recurrence of symptoms and further surgery was successful in eliminating infection in four patients. These rates of success are similar to those of other comparable series. We conclude that protracted courses of intravenous antibiotic treatment may not be necessary in the management of the infected total knee replacement. In addition, we analysed the microbiological, histological and serological results obtained at the time of re-implantation of the definitive prosthesis, but could not identify a single test which alone would accurately predict a successful outcome

Infection of a total hip replacement (THR) requires component removal and thorough local debridement. Usually, long-term antibiotic treatment in conjunction with a two-stage revision is required. This may take several months. One-stage revision using antibiotic-loaded cement has not gained widespread use, although the clinical and economic advantages are obvious. Allograft bone may be impregnated with high levels of antibiotics, and in revision of infected THR, act as a carrier providing a sustained high local concentration. We performed 37 one-stage revision of infected THRs, without the use of cement. There were three hips which required further revision because of recurrent infection, the remaining 34 hips (92%) stayed free from infection and stable at a mean follow-up of 4.4 years (2 to 8). No adverse effects were identified. Incorporation of bone graft was comparable with unimpregnated grafts. Antibiotic-impregnated allograft bone may enable reconstruction of bone stock, insertion of an uncemented implant and control of infection in a single operation in revision THR for infection

The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis

The outcome of primary management of acute osteomyelitis in 655 children treated in New Zealand between 1947 and 1976 is examined. Failure occurred in 20 per cent of children, in four-fifths of whom it was manifest by one year, and half of whom experienced one recurrence only. Lower failure rates were associated with use of bactericidal antibiotics, certain favourable sites, and age over 16 years. Surgical intervention was associated with significantly higher failure rates. The place of surgical intervention and the optimal duration of antibiotic treatment can only be determined by prospective clinical trials

Coloured bone cements have been introduced to make the removal of cement debris easier at the time of primary and revision joint replacement. We evaluated the physical, mechanical and pharmacological effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean setting time (570 seconds (. sd. 4) vs 775 seconds (. sd. 11), p = 0.01), mean compression strength (95.4 MPa (. sd. 3) vs 100.1 MPa (. sd.  6), p = 0.03), and mean bending strength (65.2 MPa (. sd. 5) vs 76.6 MPa (. sd. 4), p < 0.001) as well as its mean elastic modulus (2744 MPa (. sd. 97) vs 3281 MPa (. sd. 110), p < 0.001). The supplementation of the coloured cement with vancomycin and gentamicin decreased its mean bending resistance (55.7 MPa (. sd. 4) vs 65.2 MPa (. sd . 5), p < 0.001).The methylene blue significantly decreased the mean release of gentamicin alone (228.2 µg (. sd. 24) vs 385.5 µg (. sd . 26), p < 0.001) or in combination with vancomycin (498.5 µg (. sd. 70) vs 613 µg (. sd. 25), p = 0.018) from the bone cement. This study demonstrates several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue

We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis

More than a million hip replacements are carried out each year worldwide, and the number of other artificial joints inserted is also rising, so that infections associated with arthroplasties have become more common. However, there is a paucity of literature on infections due to haematogenous seeding following dental procedures. We reviewed the published literature to establish the current knowledge on this problem and to determine the evidence for routine antibiotic prophylaxis prior to a dental procedure. We found that antimicrobial prophylaxis before dental interventions in patients with artificial joints lacks evidence-based information and thus cannot be universally recommended

Aims

To compare the cost-effectiveness of high-dose, dual-antibiotic cement versus single-antibiotic cement for the treatment of displaced intracapsular hip fractures in older adults.

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.

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

We retrospectively reviewed 21 patients (22 shoulders) who presented with deep infection after surgery to the shoulder, 17 having previously undergone hemiarthroplasty and five open repair of the rotator cuff. Nine shoulders had undergone previous surgical attempts to eradicate their infection. The diagnosis of infection was based on a combination of clinical suspicion (16 shoulders), positive frozen sections (> 5 polymorphonuclear leukocytes per high-power field) at the time of revision (15 shoulders), positive intra-operative cultures (18 shoulders) or the pre-operative radiological appearances. The patients were treated by an extensive debridement, intravenous antibiotics, and conversion to a reverse shoulder prosthesis in either a single- (10 shoulders) or a two-stage (12 shoulders) procedure. At a mean follow-up of 43 months (25 to 66) there was no evidence of recurrent infection. All outcome measures showed statistically significant improvements. Mean abduction improved from 36.1° (. sd. 27.8) pre-operatively to 75.7° (. sd. 36.0) (p < 0.0001), the mean forward flexion from 43.1° (. sd. 33.5) to 79.5° (. sd. 43.2) (p = 0.0003), and mean external rotation from 10.2° (. sd. 18.7) to 25.4° (. sd. 23.5) (p = 0.0037). There was no statistically significant difference in any outcome between the single-stage and the two-stage group

It has been shown in experimental animals that the living cells in a bone autograft can make an important contribution to osteogenesis. However, some common clinical techniques, such as the topical use of antibiotic powders on grafts or on the graft bed, are likely to damage or kill the cells. In this experimental study in rats, bone isografts dusted with chloramphenicol or methicillin powder or with Polybactrin spray before subcutaneous implantation produced little or no new bone over a period of two weeks whereas untreated, control grafts showed abundant osteogenesis, as did grafts pretreated with solutions of antibiotics. The effect of short-term storage of the grafts for 3 to 24 hours in air, saline or culture medium before implantation was also examined. Grafts stored in culture medium generally did as well as, or better than, fresh control grafts whereas immersion in saline inhibited osteogenesis. The importance of these results for clinical bone grafting is discussed

Aims

The outcome of repeat septic revision after a failed one-stage exchange for periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat septic revision after a failed one-stage exchange, and to determine whether the Musculoskeletal Infection Society (MSIS) stage is associated with subsequent infection-related failure.

Antibiotic levels in bone and fat were measured in patients undergoing knee replacement to determine the time that should elapse between intravenous injection and tourniquet inflation. The tissue levels increased progressively with time, and there was wide variation in absorption rate between patients and between the two cephalosporins assessed. Five minutes should probably be left between systemic injection and inflation of the tourniquet, though two minutes may be long enough for drugs which are rapidly absorbed

Aims

One-stage exchange for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) is gaining popularity. The outcome for a repeat one-stage revision THA after a failed one-stage exchange for infection remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat one-stage exchange, and to investigate the association between the Musculoskeletal Infection Society (MSIS) staging system and further infection-related failure.

The treatment of infected nonunions is difficult. Antibiotic cement-coated (ACC) rods provide stability as well as delivering antibiotics. We conducted a review of 110 infected nonunions treated with ACC rods. Patients were divided into two groups: group A (67 patients) with an infected arthrodesis, and group B (43 patients) with an infected nonunion in a long bone. In group A, infected arthrodesis, the success rate after the first procedure was 38/67 (57%), 29/67 (43%) required further surgery for either control of infection or non-union. At last follow-up, five patients required amputation, representing a limb salvage rate of 62/67 (93%) overall. In all, 29/67 (43%) presented with a bone defect with a mean size of 6.78 cm (2 to 25). Of those with a bone defect, 13/29 (45%) required further surgery and had a mean size of defect of 7.2 cm (3.5 to 25). The cultures were negative in 17/67 (26%) and the most common organism cultured was methicillin-resistant staphylococcus aureus (MRSA) (23/67, (35%)). In group B, long bones nonunion, the success rate after the first procedure was 26/43 (60%), 17/43 (40%) required further surgery for either control of infection or nonunion. The limb salvage rate at last follow-up was 43/43 (100%). A total of 22/43 (51%) had bone defect with a mean size of 4.7 cm (1.5 to 11.5). Of those patients with a bone defect, 93% required further surgery with a mean size of defect of 5.4 cm (3 to 8.5). The cultures were negative in 10/43 (24%) and the most common organism cultured was MRSA, 15/43 (35%). ACC rods are an effective form of treatment for an infected nonunion, with an acceptable rate of complications.

Cite this article: Bone Joint J 2014; 96-B:1349–54

Aims

The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip arthroplasties (THAs) to establish the overall success and the influencing factors.

1. The dominant role of pathogenic staphylococci in surgical infections has been confirmed by positive isolations in 89·9 per cent of a wide variety of lesions in a hospital infective unit. Of 150 staphylococci isolated, 147 were sensitive to fusidic acid, two were slightly sensitive and only one was resistant.

2. Fusidic acid was administered as sodium fusidate to 100 patients with staphylococcal infections (including seventy-two with chronic post-traumatic osteomyelitis). Sterile swabs were achieved in seventy-seven of these patients and in the remaining twenty-three a change of flora was detected.

3. Bone samples were taken at operation from twenty-nine patients with chronic osteomyelitis who had been treated for at least five days with fusidic acid. Depending on dosage, the mean fusidic acid concentrations were 7·3 and 9·8 micrograms per gram. Corresponding levels in non-inflammatory bone samples from thirty-one patients were, depending on the duration of treatment, 12·3, 2l·3 and 25·4 micrograms per gram. The fusidic acid levels in cancellous bone were almost twice as high as those in compact bone.

4. The relevance of these findings to the use of fusidic acid therapy as an adjunct to surgical management of chronic osteomyelitis is discussed.

We report 16 orthopaedic patients who had antibiotic-associated diarrhoea (pseudomembranous colitis) after operation. There was an association with the use of cephradine and with the prolongation of prophylaxis for more than three peri-operative doses. Five cases occurred as a cluster, suggesting that the causative agent, Clostridium difficile, may be infectious in some situations.

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Aims. To describe the risk of periprosthetic joint infection (PJI) and reoperation in patients who have an acute, traumatic wound dehiscence following total knee arthroplasty (TKA). Methods. From January 2002 to December 2018, 16,134 primary TKAs were performed at a single institution. A total of 26 patients (0.1%) had a traumatic wound dehiscence within the first 30 days. Mean age was 68 years (44 to 87), 38% (n = 10) were female, and mean BMI was 34 kg/m. 2. (23 to 48). Median time to dehiscence was 13 days (interquartile range (IQR) 4 to 15). The dehiscence resulted from a fall in 22 patients and sudden flexion after staple removal in four. The arthrotomy was also disrupted in 58% (n = 15), including a complete extensor mechanism disruption in four knees. An irrigation and debridement with component retention (IDCR) was performed within 48 hours in 19 of 26 knees and two-thirds were discharged on antibiotic therapy. The mean follow-up was six years (2 to 15). The association of wound dehiscence and the risk of developing a PJI was analyzed. Results. Patients who sustained a traumatic wound dehiscence had a 6.5-fold increase in the risk of PJI (95% confidence interval (CI) 1.6 to 26.2; p = 0.008). With the small number of PJIs, no variables were found to be significant risk factors. However, there were no PJIs in any of the patients who were treated with IDCR and a course of antibiotics. Three knees required reoperation including one two-stage exchange for PJI, one repeat IDCR for PJI, and one revision for aseptic loosening of the tibial component. Conclusion. Despite having a traumatic wound dehiscence, the risk of PJI was low, but much higher than experienced in all other TKAs during the same period. We recommend urgent IDCR and a course of postoperative antibiotics to decrease the risk of PJI. A traumatic wound dehiscence increases risk of PJI by 6.5-fold. Cite this article: Bone Joint J 2021;103-B(6 Supple A):191–195

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting. Cite this article: Bone Joint J 2024;106-B(5):425–429

Aims. The aim of this study was to determine the prevalence and impact of tourniquet use in patients undergoing limb salvage surgery with endoprosthetic reconstruction for a tumour around the knee. Methods. We retrieved data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial; specifically, differences in baseline characteristics, surgical details, and postoperative functional outcomes between patients who had undergone surgery under tourniquet and those who had not. A linear regression model was created to evaluate the impact of tourniquet use on postoperative Toronto Extremity Salvage Scores (TESSs) while controlling for confounding variables. A negative-binomial regression model was constructed to explore predictors of postoperative length of stay (LOS). Results. Of the 604 patients enrolled in the PARITY trial, 421 had tumours around the knee joint, of whom 225 (53%) underwent surgery under tourniquet. The tourniquet group was younger (p = 0.014), more likely to undergo surgery for a tumour of the tibia, and had shorter operating times by a mean of 50 minutes (95% confidence interval 30 to 72; p < 0.001). The adjusted linear regression model found that the use of a tourniquet, a shorter operating time, and a higher baseline TESS independently predicted better function at both three- and six-month follow-up. The negative-binomial regression model showed that tourniquet use, shorter operating time, younger age, and intraoperative tranexamic acid administration independently predicted a shorter LOS in hospital. Conclusion. The results of this study show that in patients undergoing resection of a tumour around the knee and endoprosthetic reconstruction, the use of an intraoperative tourniquet is associated with a shorter operating time, a reduced length of stay in hospital, and a better early functional outcome. Cite this article: Bone Joint J 2022;104-B(10):1168–1173

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aims. It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. Methods. We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. Results. Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. Conclusion. Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J 2021;103-B(5):916–922

Aims. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077

Aims. Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence. Methods. A total of 508 patients who required revision surgery of total hip arthroplasty (THA) (n = 231) or total knee arthroplasty (TKA) (n = 277) because of component loosening underwent biopsy before revision surgery. The tissue samples collected at biopsy and during revision surgery were analyzed according to the criteria of the Musculoskeletal Infection Society (MSIS). Results. In total, 178 (113 THA, 65 TKA) were classified as infected. The biopsy procedure had a sensitivity of 93.8%, a specificity of 97.3%, a positive predictive value (PPV) of 94.9%, a negative predictive value (NPV) of 96.7%, and an accuracy of 96.1%. Of the 178 infected patients, 26 showed a difference in the detected bacteria from the biopsy and the revision surgery (14.6%). This difference required a change to antibiotic therapy in only two cases (1.1%). Conclusion. Biopsy is a useful tool to diagnose PJI, but there may be a difference in the detected bacteria between the biopsy and revision surgery. However, this did not affect the choice of antibiotic therapy in most cases, rendering the clinical relevance of this phenomenon as low. Cite this article: Bone Joint J 2020;102-B(3):329–335

Aims. Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. Methods. We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. Results. Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. Conclusion. Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145–150

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Aims. Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI. Methods. A total of 105 consecutive patients who underwent revision arthroplasty for chronic culture-negative PJI were retrospectively evaluated. One-stage revision arthroplasty was performed in 30 patients, while 75 patients underwent two-stage exchange, with a minimum of one year's follow-up. Reinfection, re-revision for septic and aseptic reasons, amputation, readmission, mortality, and length of stay were compared between the two treatment strategies. Results. The patient demographic characteristics did not differ significantly between the groups. At a mean follow-up of 4.2 years, the treatment failure for reinfection for one-stage and two-stage revision was five (16.7%) and 15 patients (20.0%) (p = 0.691), and for septic re-revision was four (13.3%) and 11 patients (14.7%) (p = 0.863), respectively. No significant differences were observed between one-stage and two-stage revision for 30- 60- and 90-day readmissions (10.0% vs 8.0%; p = 0.714; 16.7% vs 9.3%; p = 0.325; and 26.7% vs 10.7%; p = 0.074), one-year mortality (3.3% vs 4.0%; p > 0.999), and amputation (3.3% vs 1.3%; p = 0.496). Conclusion. In this non-randomized study, one-stage revision arthroplasty demonstrated similar outcomes including reinfection, re-revision, and readmission rates for the treatment of chronic culture-negative PJI after TKA and THA compared to two-stage revision. This suggests culture negativity may not be a contraindication to one-stage revision arthroplasty for chronic culture-negative PJI in selected patients. Cite this article: Bone Joint J 2021;103-B(3):515–521

Aims. Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods. Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results. A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion. Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45

Aims. Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available, but are significantly more expensive. We investigated whether the elution of antibiotic from ‘home-made’ cement containing vancomycin was comparable with more expensive commercially available vancomycin impregnated cement. Materials and Methods. A total of 18 cement discs containing either proprietary CopalG+V; or ‘home-made’ CopalR+G with vancomycin added by hand, were made. Each disc contained the same amount of antibiotic (0.5 g gentamycin, 2 g vancomycin) and was immersed in ammonium acetate buffer in a sealed container. Fluid from each container was sampled at eight time points over a two-week period. The concentrations of gentamicin and vancomycin in the fluid were analysed using high performance liquid chromatography mass spectrometry. Results. The highest peak concentrations of antibiotic were observed from the ‘home-made’ cements containing vancomycin, added as in the operating theatre. The overall elution of antibiotic was, fivefold (vancomycin) and twofold (gentamicin) greater from the ‘home-made’ mix compared with the commercially mixed cement. The use of a vacuum during mixing had no significant effect on antibiotic elution in any of the samples. Conclusion. These findings suggest that the addition of 2 g vancomycin powder to gentamicin-impregnated bone cement by hand significantly increases the elution of both antibiotics compared with commercially prepared cements containing vancomycin. We found no significant advantages of using expensive commercially produced vancomycin-impregnated cement and recommend the addition of vancomycin powder by hand in the operating theatre. Cite this article: Bone Joint J 2017;99-B:73–7

Aims. The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an in vitro medium environment against methicillin-sensitive Staphylococcus aureus (MSSA). Materials and Methods. Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon’s test. Results. MSSA was inhibited for 12 days by the tantalum cylinders and for nine days by the cement cylinders. At day one, the mean zone of inhibition was 28.6 mm for the tantalum and 19.8 mm for the cement group (p < 0.001). At day ten, the mean zone of inhibition was 3.8 mm for the tantalum and 0 mm for the cement group (p < 0.001). The porous tantalum cylinders soaked only with phosphate buffered solution showed no zone of inhibition. Conclusion. Compared with cement, tantalum could release antibiotics for longer. Further studies should assess the advantages of using antibiotic-loaded porous tantalum implants at revision arthroplasty. Cite this article: Bone Joint J 2019;101-B:848–851

Aims. The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT. Methods. A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures. Results. A total of 48 studies were included, with 1,386 cases treated with the IMT. Patients had a mean age of 40.7 years (4 to 88), and the mean defect size was 5.9 cm (0.5 to 26). In total, 82.3% of cases achieved union after the index second stage procedure. The mean time to union was 6.6 months (1.4 to 58.7) after the second stage. Our multivariate analysis of 450 individual patients showed that the odds of developing a nonunion were significantly increased in those with preoperative infection. Patients with tibial defects, and those with larger defects, were at significantly higher odds of developing a postoperative infection. Our analysis also demonstrated a trend towards the inclusion of antibiotics in the cement spacer having a protective effect against the need for additional procedures. Conclusion. The IMT is an effective management strategy for complex segmental bone defects. Standardized reporting of individual patient data or larger prospective trials is required to determine the optimal implementation of this technique. This is the most comprehensive review of the IMT, and the first to compile individual patient data and use regression models to determine predictors of outcomes. Cite this article: Bone Joint J 2020;102-B(12):1723–1734

Aims. The increasing infection burden after total hip arthroplasty (THA) has seen a rise in the use of two-stage exchange arthroplasty and the use of increasingly powerful antibiotics at the time of this procedure. As a result, there has been an increase in the number of failed two-stage revisions during the past decade. The aim of this study was to clarify the outcome of repeat two-stage revision THA following a failed two-stage exchange due to recurrent prosthetic joint infection (PJI). Patients and Methods. We identified 42 patients who underwent a two-stage revision THA having already undergone at least one previous two stage procedure for infection, between 2000 and 2015. There were 23 women and 19 men. Their mean age was 69.3 years (48 to 81). The outcome was analyzed at a minimum follow-up of two years. Results. A satisfactory control of infection and successful outcome was seen in 26 patients (57%). There therefore remained persistent symptoms that either required further surgery or chronic antibiotic suppression in 16 patients (38%). One-third of patients had died by the time of two years’ follow-up. Conclusion. The rate of failure and complication rate of repeat two-stage exchange THA for PJI is high and new methods of treatment including host optimization, immunomodulation, longer periods between stages, and new and more powerful forms of antimicrobial treatment should be investigated. Cite this article: Bone Joint J 2019;101-B(6 Supple B):110–115

Aims. There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls. Patients and Methods. We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m. 2. (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort. Results. The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients. Conclusion. In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91–97

Aims. Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI. Materials and Methods. A search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Staphylococcus aureus screening, the management of anti-rheumatic medication, perioperative antibiotic prophylaxis, presurgical skin preparation, the operating room environment, irrigant options, and anticoagulation. Results. Poor glycaemic control, obesity, malnutrition, and smoking are all associated with increased rates of PJI. Vitamin D replacement has been shown in preliminary animal studies to decrease rates of PJI. Preoperative Staphylococcus aureus screening and appropriate treatment results in decreased rates of PJI. Perioperative variables, such as timely and appropriate dosage of prophylactic antibiotics, skin preparation with chlorohexidine-based solution, and irrigation with dilute betadine at the conclusion of the operation, have all been associated with reduced rates of PJI. Similarly, aggressive anticoagulation and increased operating room traffic should be avoided to help minimize risk of PJI. Conclusion. PJI remains a serious complication of arthroplasty. Surgeons should be vigilant of the modifiable risk factors that can be addressed in an attempt to reduce the risk of PJI

Aims. The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups. Methods. A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm. 3. cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate. Results. For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion. These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; . sd . 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6