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

Aims. 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. Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms. Methods. Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times. Results. In the untreated biofilm, growth up to 1.8×10. 11. colony-forming units (CFU)/cm. 2. was observed. Treatment with ciprofloxacin, flucloxacillin, vancomycin, cefuroxime, and amoxicillin all with rifampicin gave 6.0 log, 6.1 log, 1.4 log, 4.8 log, and 3.6 log reduction in CFU/cm. 2. , respectively. Mechanical cleaning alone resulted in 4.9 log reduction and induction heating in 7.3 log reduction. There was an additional effect of ciprofloxacin, flucloxacillin, and induction heating when used in combinations. There was no additional effect for mechanical cleaning. No bacterial growth could be detected after induction heating followed by seven days of ciprofloxacin with rifampicin. Conclusion. Mechanical cleaning, antibiotics, and non-contact induction heating reduced the bacterial load of mature S. aureus biofilms with approximately 5 log or more as a single treatment. The effect of mechanical cleaning on mature S. aureus biofilms was limited when used in combination with antibiotics and/or induction heating. Cite this article: Bone Joint Res 2022;11(9):629–638

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. Antibiotic prophylaxis involving timely administration of appropriately dosed antibiotic is considered effective to reduce the risk of surgical site infection (SSI) after total hip and total knee arthroplasty (THA/TKA). Cephalosporins provide effective prophylaxis, although evidence regarding the optimal timing and dosage of prophylactic antibiotics is inconclusive. The aim of this study is to examine the association between cephalosporin prophylaxis dose, timing, and duration, and the risk of SSI after THA/TKA. Methods. A prospective multicentre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKA/THA at one of 19 high-volume Australian public/private hospitals. Data were collected prior to and for one-year post surgery. Logistic regression was undertaken to explore associations between dose, timing, and duration of cephalosporin prophylaxis and SSI. Data were analyzed for 1,838 participants. There were 264 SSI comprising 63 deep SSI (defined as requiring intravenous antibiotics, readmission, or reoperation) and 161 superficial SSI (defined as requiring oral antibiotics) experienced by 249 (13.6%) participants within 365 days of surgery. Results. In adjusted modelling, factors associated with a significant reduction in any SSI and deep SSI included: correct weight-adjusted dose (any SSI; adjusted odds ratio (aOR) 0.68 (95% confidence interval (CI) 0.47 to 0.99); p = 0.045); commencing preoperative cephalosporin within 60 minutes (any SSI, aOR 0.56 (95% CI 0.36 to 0.89); p = 0.012; deep SSI, aOR 0.29 (95% CI 0.15 to 0.59); p < 0.001) or 60 minutes or longer prior to skin incision (aOR 0.35 (95% CI 0.17 to 0.70); p = 0.004; deep SSI, AOR 0.27 (95% CI 0.09 to 0.83); p = 0.022), compared to at or after skin incision. Other factors significantly associated with an increased risk of any SSI, but not deep SSI alone, were receiving a non-cephalosporin antibiotic preoperatively (aOR 1.35 (95% CI 1.01 to 1.81); p = 0.044) and changing cephalosporin dose (aOR 1.76 (95% CI 1.22 to 2.57); p = 0.002). There was no difference in risk of any or deep SSI between the duration of prophylaxis less than or in excess of 24 hours. Conclusion. Ensuring adequate, weight-adjusted dosing and early, preoperative delivery of prophylactic antibiotics may reduce the risk of SSI in THA/TKA, whereas the duration of prophylaxis beyond 24 hours is unnecessary. Cite this article: Bone Jt Open 2022;3(3):252–260

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. To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI). Methods. This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed. Results. A total of 105 patients with chronic PJI were enrolled: 64 patients in the short course group and 41 patients in the long course group. For 99 of the patients, the infection was under control during a follow-up period of at least 24 months after two-stage revision. For the short course group, the mean duration of antibiotic prophylaxis after stage II reimplantation was 20.17 days (SD 5.30) and the infection control rate was 95.3%; for the long course group these were 45.02 days (SD 15.03) and 92.7%, respectively. There was no significant difference in infection control rates between the two groups (p = 0.676). Cox regression analysis found that methicillin-resistant staphylococcus infection (p = 0.015) was an independent prognostic factor for recurrence. Conclusion. After stage II reimplantation surgery of two-stage revision for chronic PJI, extended antibiotic prophylaxis for less than one month can achieve good infection control rate. Cite this article: Bone Joint Res 2021;10(12):790–796

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

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

Aims. There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. Methods. This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. Results. Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). Conclusion. Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III. Cite this article: Bone Jt Open 2022;3(4):284–290

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.

Aim. The aim of the present work was (i) to survey the situation of healthcare regarding the use of antibiotics in orthopaedics and trauma surgery in Germany, (ii) to determine which empiric antibiotic regimens are preferred in the treatment of periprosthethic joint infections (PJI) and (iii) to evaluate the hypothetical antibiotic adequacy of the applied empirical antibiotic therapy regimens based on a patient collective of a German university hospital. Method. A survey on empirical and prophylactic antibiotic therapy was conducted at German university and occupational health clinics (BG clinics), each in the specialties of orthopedics and trauma surgery. A total of 71 clinics were contacted by email. The questionnaire sent included open-ended questions on systemic antibiotic prophylaxis in primary hip arthroplasty; a distinction was made between hip arthroplasty due to femoral fractures and elective hip arthroplasty. In addition, the empirical antibiotic therapy used in PJIs was surveyed. To determine the success rate of prophylaxis and therapy according to sensitivity to the antibiotics applied, the survey results were compared with previously published data on antimicrobial treatment in n=81 PJI patients treated in our department between 2017 and 2020. Results. In 93.2% (elective) and 88.6% (fracture care) of the hospitals, 1st- and 2nd-generation cephalosporins are administered perioperatively for infection prophylaxis in primary hip arthroplasty. In contrast, empiric antibiotic treatment for PJI showed a clearly inhomogeneous therapeutic picture. Monotherapy with an aminopenicillin/betalactamase inhibitor is most frequently used (38.7%); 1st- and 2nd-generation cephalosporins are second most frequently used as monotherapy (18.2%). In addition, dual combination therapies have become established, mostly aminopenicillin/betalactamase inhibitor or 1st- and 2nd-generation cephalosporins, whose administration is supplemented with another antibiotic. The most common combination in PJI is aminopenicillin/betalactamase inhibitor + vancomycin (11.4%). The most widely used therapy (monotherapy with aminopenicillin/betalactamase inhibitor) would have covered 69.0% of PJI patients. Monotherapy with 1st- and 2nd-generation cephalosporins would have been susceptible to 57.8% of PJI patients. In contrast, a combination of vancomycin + 1st- and 2nd-generation cephalosporins would have been most effective, with an efficacy of 91.5% according to the resistograms, but this was used by only two hospitals. Conclusions. Empirical antibiotic therapy for the treatment of PJI is applied in more than half of the clinics with a single broad-spectrum beta-lactamase inhibitor antibiotic. This discrepancy between the everyday care in the clinics and the administration of clearly more effective combination therapies underlines the need for recommendation guidelines

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

Aim. The incidence of fractured neck of femur (FNOF) is increasing yearly. Many of these patients undergo hip hemiarthroplasty. High dose dual-antibiotic cement (HDDAC) has been shown to reduce rates of deep surgical site infection (SSI) when compared to the current standard low dose single-antibiotic cement (LDSAC) in a quasi-randomised controlled trial. Some concerns exist regarding the use of HDDAC and the development of resistance. We reviewed cases of infection in LDSAC and HDDAC bone cement with regard to causative organism and resistance profile. Method. A retrospective analysis was undertaken of all hemiarthroplasties within our trust from April 2008 to December 2014. We identified all patients in this time period who acquired a deep SSI from the trust SSI surveillance database. The infecting organisms and susceptibility patterns were collated for each cement. Results. We identified 1941 hemiarthroplasties. There were 36 deep surgical site infections representing an infection rate of 3.1% in LDSAC patients and 1.2% in HDDAC patients. A wider variety of organisms were seen in the LDSAC compared to HDDAC. Staphylococcus epidermidis accounted for the majority of infections in both LDSAC and HDDAC patients. Infection with Corynebacterium species and Staphylococcus aureus was eliminated completely in HDDAC. There was minimal change in the proportion of Gram-negative and Gram-positive bacteria. A change in resistance was not demonstrated amongst infections caused by Gram-negative bacteria. In Gram-positive bacteria, resistance to a number of antibiotics increased using HDDAC compared to LDSAC, most notably to clindamycin and gentamicin within the coagulase negative staphylococci. However, levels of resistance remained low to teicoplanin, vancomycin, daptomycin, linezolid and rifampicin. Conclusions. A lower infection rate was seen in HDDAC. Direct comparison demonstrated changes in resistance profiles caused by Gram-positive organisms. 24,000 patients undergo hip hemiarthroplasty annually. Extrapolating our results to this cohort would demonstrate 744 infections in LDSAC and 288 infections in HDDAC. Of these, resistance to both clindamycin and gentamicin would be seen in 180 patients with LDSAC and 177 patients with HDDAC. Overall, this review supports the continued use of HDDAC in FNOF patients. High dose dual antibiotic cement = Copal G+C, Heraeus Medical, UK. Low dose single antibiotic cement = Palacos R+G, Heraeus Medical, UK

Aims. Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance. Methods. The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital’s website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance. Results. The primary choice and dosing of the prophylactic antimicrobial regimens varied widely. The two most used regimens were combined teicoplanin and gentamicin, and cefuroxime followed by two or three doses of cefuroxime eight-hourly, recommended by 24 centres (22.02%) each. The alternative choice and dosing of the prophylactic antimicrobial regimen also varied widely across the 83 centres with data available. Prophylaxis regimens across some centres fail to cover the likeliest causes of surgical site infection (SSI). Five centres (4.59%) recommend co-amoxiclav, which confers no Staphylococcus coverage, while 33 centres (30.28%) recommend cefuroxime, which confers no Enterococcus coverage. Limited adherence to 2018 Philadelphia Consensus Guidance was observed, with 67 centres (61.50%) not including a cephalosporin in their guidance. Conclusion. This analysis of guidance on antimicrobial prophylaxis in primary arthroplasty across 109 hospitals and trusts in the UK has identified widespread variation in primary and alternative antimicrobial regimens currently recommended. Cite this article: Bone Jt Open 2023;4(10):742–749

Spondylodiscitis is a severe infectious disease of the vertebral column and the intervertebral disc space and may be complicated by an epidural abscess. A wide range of pathogens have been described as causative agents. Since several weeks of antibiotics are necessary for successful therapy detection of the causative pathogen is essential. Specific antibiotic therapy improves outcome and reduces antibiotic related complications. Antibiotic Stewardship (ABS) programs are bundled approaches aimed at improving antibiotic therapy. In 2012 an ABS program including weekly interdisciplinary clinical rounds and development of algorithms for diagnosis and therapy of patients with spondylodiscitis was established in the Department of Orthopedic Surgery in a University hospital. We evaluated the effects of ABS with regard to the appropriateness of specimen and pathogen detection and antibiotic therapy in patients with spondylodiscitis. We retrospectively analysed diagnostic procedures and pathogen detection of 100 patients that were hospitalized with spondylodiscitis and compared the data of patients that were treated before (2004–2011) and after introduction of ABS measures (2012–2014). After introduction the effect of ABS on antibiotic therapy was analysed. 100 patients with radiologically confirmed spondylodiscits were enrolled. The pre-ABS group (2004–2011) contained 58 patients. Of these no samples were taken for microbiological examination from 21 patients (36%) and from 8 patients (14%) only swabs were submitted for culture. Aspirates or tissue samples were taken from 22 patients (38%) and blood cultures from 18 patients (31%). Pathogen detection was successful in 18 patients (31%). After introduction of ABS in the beginning of 2012 aspirates or tissue samples were taken from 34 patients (81%) and blood cultures were taken from 34 patients (81%). Pathogen detection was successful in 26 patients (62%). The most commonly detected pathogens were Gram positive cocci (S.aureus, S. epidermidis, and streptococci) in 31 patients. Less common pathogens were found in 12 patients (Gram negative rods (8), fungi (3), Moraxella (1) and Propionibacterium (1). After introduction of ABS antibiotic therapy was changed in 18 of 20 patients (90%) after pathogen identification. In 50 % of cases the inappropriate empiric therapy was changed (MRSA, MRSE and Gram negative rods) and in 50 % broad-spectrum antibiotic therapy could be deescalated. ABS significantly improved the number and quality of samples, increased the number of blood cultures taken and doubled the pathogen detection rates in patients with spondylodiscitis leading to an improvement in antibiotic therapy in almost all patients with pathogen detection

This study aimed to evaluate the month-to-month prevalence of antibiotic dispensation in the 12 months before and after total knee arthroplasty (TKA) and total hip arthroplasty (THA) and to identify factors associated with antibiotic dispensation in the month immediately following the surgical procedure. In total, 4,115 THAs and TKAs performed between April 2013 and June 2019 from a state-wide arthroplasty referral centre were analysed. A cross-sectional study used data from an institutional arthroplasty registry, which was linked probabilistically to administrative dispensing data from the Australian Pharmaceutical Benefits Scheme. Multivariable logistic regression was carried out to identify patient and surgical risk factors for oral antibiotic dispensation. Oral antibiotics were dispensed in 18.3% of patients following primary TKA and 12.0% of patients following THA in the 30 days following discharge. During the year after discharge, 66.7% of TKA patients and 58.2% of THA patients were dispensed an antibiotic at some point. Patients with poor preoperative health status were more likely to have antibiotics dispensed in the month following THA or TKA. Older age, undergoing TKA rather than THA, obesity, inflammatory arthritis, and experiencing an in-hospital wound-related or other infectious complications were associated with increased antibiotic dispensation in the 30 days following discharge. A high rate of antibiotic dispensation in the 30 days following THA and TKA has been observed. Although resource constraints may limit routine wound review for all patients by a surgeon, a select cohort may benefit from timely specialist review postoperatively. Several risk factors identified in this study may aid in identifying appropriate candidates for such changes to follow-up care

Objectives. This study is to compare the elution characteristics, antimicrobial activity, and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powder antibiotic, powder antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder, and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin–loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or xylitol group. Regarding the amphotericin B–loaded ALBCs, only the eluate samples of the liquid group exhibited a clear inhibitory zone which was not observed in either xylitol nor powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the antibiotic-release efficacy than that by loading ALBC with the same dose of antibiotic powder. This simple, and effective method for preparation of ALBCs can significantly improve the antibiotic-release efficacy of ALBCs

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

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

Surgical site infections following orthopaedic surgery are a serious complication associated with increased morbidity and mortality. Intra-wound antibiotic powder may be able to provide infection prophylaxis locally with less systemic adverse effects, and promising results have been reported in systematic reviews of its use in spine surgery. This study aims to analyse the efficacy and adverse effect profile of intra-wound antibiotics in reducing surgical site infections in orthopaedic surgery for traumatic pelvic and lower limb fractures. A systematic review was conducted for studies reporting on the incidence of surgical site infections following administration of intra-wound antibiotic powder in pelvic and lower limb trauma surgery. Randomised controlled trials, cohort and case-control studies were included. A meta-analysis was conducted for deep surgical site infections. Seven studies were included in the systematic review including six retrospective case-control studies and one randomised controlled trial. Results of the meta-analysis suggest a potential 23% reduction in the odds of developing a deep surgical site infection in patients treated with intra-operative antibiotic powder compared with those managed with intravenous antibiotics alone (OR 0.77, 95% CI 0.52 – 1.13), although the results did not reach statistical significance. Notable selective bias against intra-wound antibiotics and suboptimal study design were found in the retrospective studies, however the randomised controlled trial reported a significant reduction in deep surgical site infections with intra-wound vancomycin powder. There were no reports of systemic adverse outcomes and minimal risk of wound complications with the use of intra-wound antibiotics. This review suggests the use of intra-wound antibiotic powder in pelvic and lower limb trauma surgery may reduce the incidence of deep surgical site infections. Further powered studies including randomised controlled trials are required to confirm the results highlighted in this study

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

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

Aim. The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality. Method. A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool. Results. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Conclusions. Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality

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

Aims. Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents. Methods. S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy. Results. The application of fhESWT led to a ten-fold reduction in bacterial counts on the metal discs for all impulse numbers compared to the control (p < 0.001). Increasing the number of impulses did not further reduce bacterial counts in the absence of antibiotics (all p > 0.289). Antibiotics alone reduced the number of bacteria on the discs; however, the combined application of the fhESWT and antibiotic administration further reduced the bacterial count compared to the antibiotic treatment only (p = 0.032). Conclusion. The use of fhESWT significantly reduced the colony-forming unit (CFU) count of a S. aureus biofilm in our model independently, and in combination with antibiotics. Therefore, the supplementary application of fhESWT could be a helpful tool in the treatment of IFIs in certain cases, including infected nonunions. Cite this article: Bone Joint Res 2021;10(1):77–84

Aim. Studies have shown that retention of antibiotic cement spacer in selected elderly patients with low functional demand represents a viable option for periprosthetic joint infections (PJI) treatment. 1,2. . The aim of this study is to compare the efficacy in infection treating among modular taylored preformed and hand-made antibiotic spacers. Our hypothesis is that modular tailored preformed spacer provides a better rate of infection resolution, better radiological and functional outcomes compared to hand-made spacers. Materials and methods. We identified 48 patients treated with antibiotic cement spacer for shoulder chronic infection between 2015 and 2021 in our institution; (13 hand-made spacers and 35 modular tailored preformed spacers). We collected data about comorbidities, associated microorganism, infection resolution, clinical and radiographic evaluation. Results. The mean age at surgery was 63.2 years, (45.8% female − 54.2% male), mean BMI 28.3. The mean time of infection diagnosis after first surgery was 30 months; (31.2% infection after ORIF in proximal humeral fractures, 68.8% PJI after shoulder arthroplasty). The main pathogens were Propionibacterium Acnes (37.5%), Staphylococcus Epidermidis (29.2%), Staphylococcus Aureus (16.7%), negative intraoperative coltures (14.6%), Enterococcus (4.17%), Pseudomonas Aeruginosa (4.17%). The mean time of antibiotic spacer retention was 18 months: 23 patients (47.9%) underwent second stage surgery for prosthesis implantation; 2 removed the spacer because of spacer dislocation, 2 died during follow up; while 21 patients still hold the antibiotic spacer (17 patients in treatment with prefabricated spacers and 4 with self-constructed spacer). The mean value for clinical assessment for patients with modular tailored preformed spacer were: Constant Score 34 – QuickDASH 40 – SST 33 – ASES Score 66 – VAS 2. Patients treated with hand-made spacer registered the following scores: Constant Score 20 – QuickDASH 51 – SST 25 – ASES Score 38 – VAS 6. Two patients presented fracture of the spacer (one hand-made spacer and one tailored preformed). Conclusions. According to our data patients treated with modular tailored preformed antibiotic spacer show better functional outcomes. Patients are more likely to retain the spacer as a permanent implant, avoiding the risks of a second stage surgery in those low-demanding patients, achieving a reasonable satisfying quality of shoulder motion without pain

Background and aim. In 2019, specific diagnostic and antibiotic treatment recommendations for diabetic foot infection (DFI) and osteomyelitis (DFO) were introduced in our institution. They include principles on numbers of biopsies to obtain for microbiological/histopathological examinations, labeling anatomic localization, and antibiotic treatment (ABT) duration based on the aforementioned findings. ABT should be stopped after complete resection of infected bone. In case of incomplete resection, treatment is continued for 4–6 weeks. Two years after the introduction of these recommendations, we investigated the degree of implementation for hospitalized patients. Method. Adult patients with DFI/DFO undergoing surgical intervention from 01/2019–12/2021 were reviewed retrospectively. Diagnostic procedures were assigned to each episode when performed ≤30 days before surgical invention. Chi-square and Mann-Whitney-U tests were performed where appropriate. Results. We included 80 patients with 117 hospital episodes and 163 surgical interventions (mean 1.5 episodes and 2 interventions per patient). The mean age was 69.6 (SD 11.5) years, 75% were male. Vascular examination and MRI were performed in 70.9% and 74.4% of episodes, respectively. Impaired perfusion and DFO were confirmed in 34.9% and 56.3%, respectively. Blood cultures were sampled in 34.2%, bacteremia detected in 7.7% with S. aureus being the most common microorganism. Biopsies were obtained in 71.8% of operations, in 90.5% of those 3–5 samples. These were sent for histological examination in 63.2% of the interventions. In 43.6% the anatomic location was labeled ‘proximal to the resection margin’. Preoperative antibiotics were administered in 41.9% of the episodes because of concomitant soft-tissue infections. The most commonly used compound was amoxicillin/clavulanate (74.4%). ABT duration varied significantly when there were signs of DFO in preoperative MRI (p=0.015). The mean duration of antibiotic therapy was 9 (IQR 5–15) days in surgically cured episodes and 40.5 (IQR 15–42) days in cases with resection margins in non-healthy bone (p<0.0001). The results were similar when analyzing treatment duration with respect to osteomyelitis in histology: 13 (IQR 8–42) versus 29 (IQR 13–42) days, respectively (p=0.026). Conclusions. The adherence to recommendations in terms of biopsy sampling was excellent, moderate for sending samples to histology and poor for labeling the anatomic location. The adherence to ABT duration was good but can be improved by shortening treatment duration for surgically cured cases. Results of preoperative MRI appear to be influential on the decision-making for treatment duration

Aim. Multispecies biofilms are associated with difficult periprosthetic joint infections (PJI), particularly if they have different antibiotic sensitivities. We aimed to determine if we could generate and kill a multispecies biofilm consisting of a Gram negative and Gram positive pathogen in-vitro with antibiotic loaded calcium sulfate beads containing single or combination antibiotics. Methods. To establish whether we could co-culture mixed species biofilms various combinations of Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Staphylococcus aureus (SA) and Enterobacter faecalis (EF) were grown together on 316L stainless steel coupons and agar plates. Based on this screen we focused on PA + EF and challenged them with high purity calcium sulfate beads (Stimulan Rapid Cure) loaded with vancomycin (V), alone tobramycin (T) alone or vancomycin and tobramycin in combination (V+T). Bioluminescence, light imaging, plate count, confocal microscopy and scanning electron microscopy were used to quantify growth. Results. On 316LSS the V loaded bead reduced both EF and PA by approximately 2 logs compared to unloaded control beads. A T alone loaded bead eliminated PA from the dual species biofilm and caused a 2-log reduction in EF. The V+T-beads reduced PA by 9-logs and EF by 8.3 logs. In terms of total CFUs V+T beads reduced the bioburden by 8.4 logs compared to V or T alone. which resulted in 2.1 and 2.6 log reductions respectively. (* P<0.05, *** P<0.001). On agar PA dominated the culture for the unloaded and V loaded beads. However, when challenged with a T loaded bead both species were able to coexist and a zone of killing was generated in both species in the multispecies biofilms. However, this zone was smaller and included more tolerant variants than the zone generated by V+T-loaded beads. Conclusions. There were species proportion differences between biofilms grown on agar and 316LSS demonstrating the importance of growth conditions on species interactions. Antibiotics against strains with differing sensitivities can shift species interactions. High purity calcium sulfate beads containing tobramycin a broad-spectrum Gram positive and negative antibiotic vancomycin, a Gram-positive targeted antibiotic killed a larger percentage of a multispecies in an in-vitro biofilm than either single gram-specific antibiotic alone, demonstrating the advantage of using combination antibiotics for treating multispecies biofilms

Staphylococcus aureus osteo-articular infections (OAI) are frequently accompanied by blood stream infections (BSI) diagnosed by positive blood culture (BC). Microbiological protocols in adults advise prolonged intravenous antibiotics and repeat BC 48-hourly in the presence of a BSI, however evidence to support the systematic employment of these guidelines in paediatric patients is lacking. We aimed to determine whether there was an increased incidence of orthopaedic and systemic complications in patients with s aureus BSI, and whether a shorter duration of intravenous antibiotics was associated with the development of complications. Following ethical approval, the departmental surgical database was searched for patients that underwent surgery for acute OAI over a 5-year period. Patients with no sample taken for BC were excluded, as were those with other or no organisms identified from any site. Demographic and clinical data were captured, including duration of IV antibiotics and development of complications. Statistical significance was set at p<0.05. Following exclusions, 44 patients with a median age of 85 months remained to be analysed. Thirty patients (68%) had a positive BC. A positive BC was associated with a higher rate of systemic complications (p=0.026) but not orthopaedic complications (p=0.159). Patients who had developed any complication had a significantly longer duration of IV antibiotic treatment compared to those without complications (p<0.001). The presenting CRP levels were significantly higher in patients that developed complications (p=0.004). Patients with staphylococcal BSI in association with an OAI are at increased risk of developing systemic complications. In our cohort, a shorter duration of antibiotic use was not associated with the development of complications, which does not support the systematic use of long courses of IV antibiotics in s aureus BSI. Further research will be required to determine the ideal protocol for these patients

Aim. Septic arthritis is a painful infection of articular joints that is typically treated by irrigation & debridement along with antibiotic therapy. There is debate amongst the medical community whether antibiotic administration should be delayed until fluid cultures have been taken to improve culture yield. However, delaying antibiotics can also have negative consequences, including joint destruction and sepsis. Therefore, the purposes of this study were to determine: 1) whether delayed antibiotic treatment affects culture yield and prognosis and 2) if the culture yield of patients treated for septic arthritis differs for hip, knee, and shoulder based on timing of antibiotic administration. Method. A retrospective analysis was conducted on 111 patients with septic arthritis of the hip, knee, or shoulder admitted from 3/2016 to 11/2018. In patients with multiple septic joints, each joint was analyzed individually (n=122). Diagnosis was determined by the treatment of irrigation & debridement and/or a positive culture. Patients without all intervention times recorded or with periprosthetic joint infection were excluded. Demographics, laboratory tests, culture results, and intervention times were obtained through chart review. Patients were grouped based on antibiotic therapy timing: >24 hours prior to arthrocentesis (Group 1), between 24 hours and 1 hour prior (Group 2), and 1 hour prior to post-arthrocentesis (Group 3). Analysis was conducted using chi-squared tests. Results. The mean age of each group were similar: Group 1 (n=38) 55.7 years, Group 2 (n=20) 57.2 years, and Group 3 (n=64) 54.8 years. No difference was observed in culture sensitivity between groups (p=0.825) with 71.1% (27/38) positive cultures in Group 1, 75% (15/20) in Group 2, and 76.6% (49/64) in Group 3. Similarly, frequency of related readmissions within 90 days (p=0.863) did not significantly vary: 26.3% (10/38) in Group 1, 20% (4/20) in Group 2, and 25% (16/64) in Group 3. Additionally, there were no significant differences in culture sensitivity in the knee (p=0.618; Groups: 87.5%, 75%, 70.6%), shoulder (p=0.517; Groups: 77.8%, 66.7%, 90%), and hip (p=0.362; Groups: 61.9%, 80%, 80%). Conclusions. Culture sensitivities and rates of readmission were similar for all patients regardless of antibiotic administration timing. These results suggest that antibiotic administration should not be delayed in septic arthritis to improve culture yield. However, the data does not suggest that early antibiotic administration will result in better clinical outcomes by lowering readmission rates. Further research is needed to better determine the clinical benefits that early administration of antibiotics may have on patient outcomes

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

Aim. Deep infection following endoprosthetic replacement (EPR) of long bones is a devastating complication occurring in 15% of musculoskeletal tumour patients. The recently published PARITY Trial demonstrated that extending antibiotic prophylaxis from 24 hours to 5 days does not reduce infection rates. However, questions remain about the optimal antibiotic choice and dose. Method. A 23-question multiple-choice questionnaire was designed and piloted through an iterative feedback process until the final version was agreed by all authors. Open and closed-ended questions were used to gather information on practice and Likert-type scale responses were used to grade responses to ascertain surgeon perceptions and preferences. The online survey was sent to all surgeon delegates of the 34th Annual Meeting of the European Musculo-Skeletal Oncology Society in London in October 2022. Results. Amongst 61 respondents, 43 were based in Europe and 18 outside of Europe. The majority (48/61) had been in clinical practice over 11 years. Antibiotic choice. 1st or 2nd generation cephalosporins were the first line choice practiced among 49 (80.3%) of respondents. Of these, 39 responded had a 2nd line protocol for beta-lactam allergy which was most commonly clindamycin (18), vancomycin (11) or a combination of a glycopeptide or clindamycin plus gentamicin (4). Respondents changed their first line regimen for radiotherapy in 6/61, chemotherapy in 8/61 and tumour site in 20/61. Re-dosing. Intraoperative re-dosing intervals of 1st and 2nd generation cephalosporins ranged from 2 to 8 hourly. Re-dosing for blood loss ranged from never to when 2 litres was lost. Of the 47 respondents, 24 said intraoperative re-dosing is always reliably administered. Duration. Six (10%) of 61 respondent routinely cover the intraoperative period only, whereas 30 (49%) give 24 hours, 16 (give 48 hours or longer and 8 continue until surgical drains are removed. 31 of 61 change duration depending on clinical situation. The most common reasons for changing were patient risk factors, soft tissue status and previous radiotherapy. 57/61 surgeons were aware of the PARITY Trial. When these respondents were asked whether they had changed practice based on PARITY, 12 said yes, 24 said no and 21 said they always give 24 hours anyway. Conclusions. Amongst an international cohort of orthopaedic oncology surgeons there was a wide variation in practice. Further research should focus on the optimum choice and re-dosing strategy, which have not been defined

Aims. Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy. Methods. A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained. Results. The overall infection rate of SSI was zero. Neither in the PAP group (n = 69) nor in the control group (n = 109) were signs of postoperative infection observed. Observed symptoms of ADEs were three-times higher in the PAP group when compared to the control-group (16.3 vs 5.5%; p = 0.043). No major ADEs were observed, but one in ten patients in the PAP group reported mild to severe intestinal or hypersensitivity symptoms. Conclusion. We demonstrate that the number needed to treat (NNT) with PAP to prevent one postoperative infection in soft-tissue arthroscopies of the wrist is > 109. Conversely, symptoms of ADEs were reported by one out of ten patients given PAP. Considering the high NNT to prevent postoperative infection and the large number of ADEs caused by PAP, we recommend not to use PAP routinely in soft-tissue arthroscopies of the wrist. Subsequent large-scale studies should be conducted to substantiate these results. Cite this article: Bone Jt Open 2023;4(4):219–225

Aim. The aim of this study is to evaluate if the gentamycin elution from bone cement is influenced by the timing of application of the antibiotic powder. Method. This was an experimental in vitro study that compared the elution properties of different formulation of gentamycin from a commercially available hip, knee and shoulder cement spacers. Four different experimental models were prepared. Five different spacers were prepared for each experimental mode and for each joint. We compared four different formulation of cement spacers: spacer #1, in which the spacer was prepared with a premixed bone-cement antibiotic mixture; spacer #2, in which the spacer was prepared by adding antibiotic powder to the bone cement at the time of spacer preparation; spacer #3, in which the spacer was prepared as spacer #2 but was stored for two months before starting the experiment; spacer #4, in addition to the gentamycin, other two antibiotics (tobramycin and vancomycin) were added to the bone cement. Gentamycin concentration was documented at seven intervals of time: T0 = 0h, T1 = 1h, T2 = 24h, T3 = 1W, T4 = 2W, T5 = 1M, T6 = 3M and T7 = 6M. The gentamycin elution at each interval of time was evaluated by using a T-student test. Results. Spacer #2, in which the gentamycin powder was added to the bone cement at the time of spacer preparation showed the higher gentamycin elution at each interval of time observed. In addition, Spacer #1, in which gentamycin powder was premixed with the bone cement showed a higher gentamycin elution when compared with spacer #3, in which the spacers were stored for two months to simulate the preformed spacers. Lastly, the addition of different antibiotic to the bone cement increases the gentamycin elution from the spacers (as demonstrated by spacer #4 model). Conclusions. a higher gentamycin elution was observed if spacer was prepared at the time of surgery when compared with preformed spacer. Lastly, our study confirmed the synergistic effect of adding one or more antibiotics with the aims to increase gentamycin elution

Aim. Debridement, antibiotics, and implant retention (DAIR) is a viable treatment option for acute periprosthetic joint infections (PJI). The landmark DATIPO trial of Bernard et al. concluded that six weeks is not non-inferior to 12-week antibiotic therapy for DAIR. However, it is unknown if suppressive antibiotic treatment (SAT) would improve patient outcomes. Therefore, our study aims to evaluate the utility of SAT after 12 weeks of therapy. Method. We performed a retrospective study of patients with acute hip or knee PJI managed with DAIR at five institutions; in the U.S. (n=1), Netherlands (n=3), and Spain (n=1) from 2005–2020. We analyzed the effect of SAT using a Cox model among patients after 12 weeks of antibiotic treatment. The primary covariate of interest was whether the patient was on antibiotics after week 12, which was coded as a time-varying covariate. We decided a-priori to control for the clinically important risk factors such as age, sex, type of infection, modular exchange, joint, and presence of bacteremia and Staphylococcus aureus. We excluded patients who died, had treatment failure, or were lost to follow-up before 12 weeks. We defined treatment failure as infection recurrence (same or different organism), unexpected reoperation, or death due to infection. Results. There were 504 patients included in the study. The majority were female (58%, n=292), with a mean age of 70 years ago (SD 11). Hips and knees were equally proportioned. Primary arthroplasties represented 69% of the total cohort (n=349). Treatment failure was 11.9% in the total cohort (n=60). There was no statistically significant association between SAT after 12 weeks and treatment failure (HR 1.25, p=0.45, 95% CI 0.70–2.24). This finding was consistent across different subgroups, including hip or knee joints, early or late acute infections, cohort, and a subgroup of knee joints after 180 days. Conclusions. SAT after 12 weeks of antibiotic treatment for acute PJI managed with DAIR does not appear to improve patient outcomes

Aim. The primary aim of this quality improvement project was to assess compliance with BOAST 4 guidelines for the delivery of antibiotic prophylaxis in patients presenting to a major trauma centre with open limb fracture and evaluate the impact of implemented changes on attainment of these guidelines. Secondary aims were to assess adherence to local guidelines for the type of antibiotic prescribed. Method. A multi-cycle audit and quality improvement project was carried out for all patients presenting to Brighton and Sussex University Hospitals NHS Trust (BSUH) with open limb fractures from 1st September 2018 to 31st January 2019, and 1. st. November 2019 to 31. st. March 2020. Patients were identified through retrospective screening of electronic operation records (Bluespier) by authors, and paper records were subsequently reviewed for data pertaining to antibiotic prescriptions. Following the initial audit cycle, targeted teaching was carried out for orthopaedic trainees, new posters were placed in key clinical areas to highlight local guidelines, and alterations to the trauma clerking proforma were implemented, to include BOAST 4 guidelines. Results. In cycle 1, a total of 52 patients received surgical treatment for open limb fractures, of which 48 (92.3%) were prescribed antibiotics prior to definitive management, with a mean time to administration of 271 minutes. Of these, 41 (78.8%) received prescriptions according to BSUH guidelines. The use of STAT prescriptions was found to significantly reduce the mean time to administration from 298 minutes to 144 minutes (p = 0.044). In cycle 2, a total of 29 patients received surgical treatment for open limb fractures, of which all 100% were prescribed antibiotics prior to definitive management, with a reduced mean time to administration (233 minutes). Of these, 26 (89.7%) received prescriptions according to BSUH guidelines, and a significantly greater proportion (p = 0.0003) received initial STAT ‘once-only’ prescriptions (51.7% vs. 15.4%). Conclusions. This quality improvement project has demonstrated the successful implementation of targeted changes to improve the attainment of BOAST 4 guidelines. Following a multi-cycle audit, all patients now receive antibiotic prophylaxis, with a higher proportion receiving antibiotics according to local BSUH guidelines. Furthermore, the use of STAT ‘once-only’ prescriptions, which was shown to be beneficial during the first audit cycle, has now significantly increased following intervention

C. Difficile infections in elderly patients with hip fractures is associated with high morbidity and mortality. Antibiotic regimens with penicillin and its derivatives is a leading cause. Antibiotic prophylactic preferences vary across different hospitals within NHS. We compared two antibiotic prophylactic regimens - Cefuroxime only prophylaxis and Teicoplanin with Gentamicin prophylaxis in fracture neck of femur surgery, and evaluated the incidence of C. Difficile diarrhea and Surgical Site Infection (SSI). To assess the Surgical Site Infection and C. Difficile infection rate associated with different regimens of antibiotics prophylaxis in fracture neck of femur surgery. Data was analyzed retrospectively. Neck of femur fracture patients treated surgically from 2009 in our unit were included. Age, gender, co morbidities, type of fracture, operation, ASA grade was collected. 1242 patients received Cefuroxime only prophylaxis between January 2009 and December 2012 (Group 1) and 486 patients received Teicoplanin with Gentamicin between October 2015 and March 2017 (Group 2). There were 353 males and 889 female patients in Group 1 and 138 males and 348 female patients in Group 2. The co morbidities in both groups were comparable. Incidence of C. Difficile diarrhea and Surgical Site Infection (SSI) was noted. Statistical analysis with chi square test was performed to determine the ‘p’ value. C. Diff diarrhea rate in Group 2 was 0.41 % as compared to 1.29 % in Group 1. The Surgical Site Infection (SSI) rate in Group 2 was 0.41 % as compared to 3.06 % in Group 1. The comparative results were statistically significant (p = 0.0009). Prophylactic antibiotic regimen of Teicoplanin with Gentamicin showed significant reduction in C. Difficile diarrhea & Surgical Site Infection in fracture neck of femur patients undergoing surgery

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

Aim. In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes of the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. Therefore, the aim of this study was to analyze the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII. Furthermore, changes of the microbiological spectrum, distribution of mono vs. polymicrobial infections, and changes of the antimicrobial resistance profile in persistent microorganisms were evaluated. Method. A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Overall, 20 patients (6 male/14 female) underwent 82 revisions for PSII (median 3; range 2–12). There were 55/82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test. Results. In total, 74 microorganisms (83.3% gram-positive; 10.8% gram-negative) were identified. The most common microorganisms were Staphylococcus epidermidis (18.9%) and Cutibacterium acnes (18.9%). All S. epidermidis identified were methicillin-resistant (MRSE). Overall, there were 15/55 (27.3%) polymicrobial infections. The microbiological spectrum changed in 57.1% (20/35) between the revision stages over the entire PSII period. In 42.9% (15/35) the microorganism persisted between the revision surgeries stages. Overall, changes of the antibiotic resistance pattern were seen in 17.4% (8/46) of the detected microorganisms comparing index revision and all subsequent re-revisions. Moreover, higher resistance rates were found for moxifloxacin and for ciprofloxacin at first re-revision surgery compared with index PSII revision. Resistances against vancomycin increased from 4.5% (1/23) at index PSII revision to 7.7% (2/26) at first re-revision surgery. Conclusions. Changes of the microbiological spectrum and the resistance pattern can occur in patients with severe PSII who require multiple revision surgeries. It is important to consider these findings in the antimicrobial treatment of PSII. The microbiological analysis of intraoperative tissue samples should be performed at every revision procedure for PSI

Aim. Prosthetic joint infection (PJI) is a devastating and costly complication of total joint arthroplasty (TJA). Use of extended oral antibiotic prophylaxis (EOAP) has become increasingly popular in the United States following a highly publicized study (Inabathula et al) from a single center demonstrating a significant protective effect (81% reduction) against PJI in ‘high-risk’ patients. However, these results have not been reproduced elsewhere and EOAP use directly conflicts with current antibiotic stewardship efforts. In order to study the role of EOAP in PJI prevention, consensus is needed for what defines ‘high-risk’ patients. The revision TJA (rTJA) population is an appropriate group to study due to having a higher incidence of PJI. The purpose of the current study was to rigorously determine which preoperative conditions described by Inabathula et al. (referred to as Inabathula criteria (IBC)) confer a higher rate of PJI in patients undergoing aseptic rTJA. Method. 2,256 patients that underwent aseptic rTJA at a single high-volume institution between 2016–2022 were retrospectively reviewed. Patient demographics and comorbidities were recorded to determine if they had 1 or more ‘IBC’, a long list of preoperative conditions including autoimmune diseases, active smoking, body mass index (BMI)>35, diabetes mellitus, and chronic kidney disease (CKD). Reoperation for PJI at 90-days and 1-year was recorded. Chi-squared or Fischer's exact tests were calculated to determine the association between preoperative presence/absence of IBC and PJI. Multivariable logistic regressions were conducted to determine if specific comorbidities within the IBC individually conferred an increased PJI risk. Results. 1223 patients (54.2%) had at least one IBC condition. IBC-positive patients were more likely to be female, have an increased ASA score, and higher BMI. IBC-positive patients had a significant increase in PJI risk at both 90-days (relative risk (RR)=2.32, p<0.0001) and 1-year (RR=2.14, p=0.002) versus IBC-negative patients. Within IBC-positive patients, every additional IBC condition conferred a 1.8× odds increase for 90-day PJI (p<0.0001), and 1.76× odds increase in 1-year PJI (p<0.0001). Multivariable logistic regression identified active smoking, BMI>35, CKD, and diabetes mellitus as being independently associated with PJI development (p<0.05). Conclusions. Over half of rTJA patients meet IBC and could be eligible to receive EOAP in the United States. However, the specific presence of active smoking, BMI>35, CKD, and diabetes mellitus appear to be responsible for the increased risk of PJI. Prospective studies investigating EOAP use for patients with these specific conditions are urgently needed to prevent unnecessary antibiotic use

Introduction. Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. Objectives. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic. Materials and method. Seventy two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as bone allograft. In the experimental groups, in 1 group - the defects were filled with bone allografts, in 2 group – Perforated Gentamycin-impregnated bone allografts. The control group did not receive any filling. The animals were killed after 14, 30 and 60 days. Evaluations consisted of X-ray plain radiography, histology at 14-, 30- and 60-days post-surgery. Results. Active osteoblast activity and active formation of new bones were detected around the defect area in all groups, but the amount of new bone formation was greater in the experimental groups than the control group. We found no statistically significant differences in the rate of bone formation between 1 and 2 groups at 14, 30 and 60 days in any of the parameters studied. X-ray results showed no significant difference in bony callus formation around allografts in 1 and 2 groups. In contrast, no significant callus formation was observed in the control group. Conclusion. The use of gentamycin-impregnated bone allografts may be of value in procedures performed at the site of osteomyelitis which require a second stage reconstruction with impacted bone grafting techniques

We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. We aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. We also compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis- contaminated polyetheretherketone (PEEK) screws in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. Bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels on days 0, 6, 20, and 28. Combination antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during early infection compared to the control group. Short- term celecoxib treatment showed similar radiological results without a reduction in treatment success (88.9%). No differences in the inflammatory markers were observed. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy

Aim. In this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. Specifically, we aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. In addition, we compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Method. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis-contaminated polyetheretherketone (PEEK) screws (1.5 × 10. 6. CFU per screw) in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. After implantation, bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels at four time points (day 0, 6, 20, and 28). Results. The combination of antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during the early post-infection period compared to the control group. Short-term celecoxib treatment showed similar radiological results, however, there was no significant reduction in treatment success in the celecoxib group (88.9%). No differences in the selected inflammatory markers were observed. Conclusion. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy. This study suggests that celecoxib may be a useful addition to the multimodal approach to pain management in orthopaedic device-related infections

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

Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection. Cite this article: Bone Joint Res 2024;13(3):101–109

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

Introduction. Management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a challenging task. Antibiotic management remains elusive due to differences in epidemiology and resistance between countries and reports. Increasing resistance of bacteria is a concern. The aim of this study was to investigate the development of antibiotic resistance of main causative bacteria in a single center. Methods. A retrospective review of all revision TKA between 2006 and 2018 in a tertiary referral center was performed. Included were cases meeting the consensus criteria for PJI with at least two positive cultures. Three chronological groups were created using a two-step cluster analysis. Results. In 129 cases of PJI there were 161 different bacteria identified by growth in culture. Of all bacteria 76.4% were gram positive, 23.6% were gram negative. Coagulase-negative Staphylococci (CNS) were diagnosed in 46.6% cultures, followed by Staphylococcus aureus in 19.8% of cultures. Overall antibiotic resistance (p=0.454) and Staphylococcus aureus resistance (p=0.788) have not increased during the study period. CNS resistance to teicoplanin (4% to 44%; p<0.001), fosfomycin (16% to 44%, p=0.016) and tetracycline (0% to 28%, p=0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and remained the most effective agent. Conclusion. The increasing resistance to several antibiotics over a little more than a decade is concerning. This study suggests that referral centres should continuously monitor obtained cultures as this has significant implications for both prophylactic treatment in primary as well as empirical antibiotic treatment in PJI. Resistance profiles may differ between centres and are subject to dynamic changes

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

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

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

Introduction. We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We . hypothesized. that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Methods. Study groups. included infected and non-infected (1) control, (2) systemic ceftriaxone (daily), (3) local tobramycin, (4) local doxycycline and (5) controlled release doxycycline. With IACUC approval, (10 rats/group; power =0.8), 50-μl, 10×4 CFU Staphylococcus aureus, slowly injecting into distal femoral medullary canal, reliably created joint infection. Antibiotic formulation was introduced locally into cavity and joint, pin was inserted, and tissues closed. After 4-weeks, serum, pin, bone and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on surface of pin, histopathology identified tissue response, liquid chromatography/mass spectrometry measured plasma antibiotic. Kruskal-Wallis one-way ANOVA compared groups. Results. Groups receiving antibiotic reported lower CFU/ml in synovium compared with control (no treatment) group (1b), but there was no difference between systemic, free or controlled antibiotics (1a). Different results with different antibiotics were shown, with free tobramycin reducing CFU/ml to a greater extent than free doxycycline in the synovium (2) (p<0.05). Antibiotic in plasma was nondetectable all groups (3). SEM revealed some biofilm on pin in all groups. . Limitations. include inoculation method, single observation period, administration of only one bacterial and antibiotic dose, and not including pairing local and systemic antibiotic. Conclusion. There was no difference in infection reduction nor detectable antibiotic in serum for any antibiotic formulation, but CFU's in synovium differed based on antibiotic formulation. For any tables or figures, please contact the authors directly

Introduction. The management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection. Materials & Methods. A retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union. Results. This approach was associated with successful treatment in 51/55 (93%) patients. Fracture union was achieved in 52/55 (95%) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98%) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13%) pathogens isolated from intra-operative samples demonstrated multi-drug resistance. Conclusions. Initial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93% of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature

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

Aims. High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder. Methods. Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT. Results. There were no differences in eradication of bacteria when vancomycin powder was used in combination with NPWT (4.5% of baseline) compared to vancomycin powder with a wound pouch dressing (1.7% of baseline) (p = 0.986), even though approximately 50% of the vancomycin was recovered in the NPWT exudate canister. Conclusion. The antimicrobial efficacy of the vancomycin powder was not diminished by the application of NPWT. These topical and locally applied therapies are potentially effective tools that can provide quick, simple treatments to prevent infection while providing coverage. By reducing the occurrence of infection, the recovery is shortened, leading to an overall improvement in quality of life. Cite this article: Bone Joint Res 2021;10(2):149–155

Prevention and treatment of total joint infection is closely related to biofilm formation and concentration of antibiotics achieved in the area around the implants. Most total joint infections are caused by bacteria that enter the wound at the time of the operation. These bacteria can attach to surfaces and rapidly form biofilm that is highly resistant to antibiotics. Prophylactic antibiotics given intravenously achieve concentration of local antibiotics in the knee in response to intravenous antibiotics about 1/3 of that achieved in the serum, and the level is transient. This may be enough to treat the planktonic form of the bacteria, but far from enough to treat the biofilm. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and cost analysis shows remarkable monetary benefit to this effect. Infected total joints benefit especially from direct application of antibiotics to the local area. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (average of 6.8 and 9,242µg/mL, respectively). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were thousands of times higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics. Preventing and treating infection in orthopaedic implant surgery requires achieving concentrations that are above the minimal biofilm eradication concentration. This can be achieved only with direct application

Objectives. The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51

Aim. Revision surgery and debridement and implant retention are recognised approaches for managing prosthetic joint infections (PJI) but may not always be indicated. If the patient is unable to have or declines surgery, prolonged suppressive antibiotic therapy (PSAT) is an option. This study aims to define outcomes of PSAT from a single unit. Method. A retrospective study was performed. All cases of PJI involving the hip or knee between 2012 and 2017 were identified from our institutional database and cross referenced with patient notes. One hundred and seventy eight cases were identified. Of these, 23 (12.9%) (10 hips, 13 knees) were treated with PSAT. Infection was diagnosed based on the MSIS criteria in all cases and all cases were managed by a multidisciplinary team which included specialist microbiologists. One case of long term antifungal therapy was additionally identified. Co-morbidity was assessed using the Charlson co-morbidity index. Exacerbations of infection and need for further surgery were recorded. Results. The mean age was 72 years (Range 35–93 years). The mean Charlson-score was 4.3 (range 1–7). Mean follow up was 24 months (Range 1–54 months). Antibiotics were commenced within 3 months of surgery in 20 cases and between 2 and 4 year following surgery in the remainder. Prolonged antibiotic therapy followed debridement and implant retention in 12 cases, single stage revision in 4 cases and 2 stage revisions in 3 cases. The average number of surgical procedures undergone by each patient prior to starting antibiotic suppression therapy was 1.8 (Range 1–4 procedures). Staphylococcal species were isolated in 13 cases (MRSA 1, MSSA 5, Staph. Epidermidis 5, CONS 1, Staph Pasteuri 1). Escherichia Coli and Streptococci were isolated in 2 cases each. Four cases were due to polymicrobial infection. No organisms were identified in 2 cases. Candida Albicans was identified in 1 case. All cases of infection were treated with prolonged oral antibiotics. Twenty patients (87%) received 6 weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics. Two patients experienced persistent symptoms and required amputation (both TKA). One immunocompromised patient required admission for sepsis related to their infected TKA. The success rate of long term suppressive antibiotics was 87% (20/23) successful at an average 2 year follow up. There was persistent wound discharge in 1 case (4.3%). Conclusions. Prolonged suppressive antibiotic therapy is an effective option for management of PJI and related symptoms with a low incidence of complications in surgically resistant PJI

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

Gram-negative organisms are increasingly seen as causative pathogens in orthopaedic fracture surgery, which might necessitate a change in antibiotic prophylaxis protocols. A single-centre retrospective review of antibiogram results from all patients treated for fracture-related infection (FRI) was conducted. Subgroup analysis was undertaken to identify any host, injury or treatment variables predisposed to Gram-negative infection. The bacteriological results of 267 patients who underwent surgical treatment for FRI were analysed. Pathogens were isolated in 216 cases (81%), of which 118 (55%) were Gram-negative infections. Fractures involving the tibia and femur (p=0.007), the presence of soft tissue defect (p=0.003) and bone defects (p=0.001) were associated with an increased risk of developing a Gram- negative FRI. Gram-negative fracture-related infections were associated with injuries experiencing bone loss and those requiring soft tissue reconstruction. It is, therefore, prudent to consider extended Gram-negative directed antimicrobial prophylaxis in these cases to prevent the development of fracture-related infection

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

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

Aim. Bone and joint infections (BJI) need frequently prolonged antibiotic treatment at high dosage for a total of 6 or 12 weeks depending the type of infection. Impact of such prolonged antibiotic exposure on the gut microbiota has never been assessed. Method. We performed a national multicentric prospective study of patients with BJI to monitor the gut microbiota dynamic all along antimicrobial treatment. Clinical data and stool collection were performed at the baseline visit (B) within 24h before starting antibiotics, at the end of the treatment (EOT) and 2 weeks after antibiotic withdrawal during a follow-up visit (FU). Microbiota composition was determined by shotgun metagenomic sequencing. Biological markers of gut permeability and inflammation were monitored at each time point. Results. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI and 21 prosthetic joint infections (PJI). At EOT there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI but not in patients with osteosynthesis-related BJI (p<0.05, Wilcoxon test). At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. Principal Component Analysis (PCoA) of the Bray Curtis distance, showed a significant change of the gut microbiota at the end of treatment compared to baseline (p<0.01, PERMANOVA) that only partially recover at FU. The taxonomic analysis showed that microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks to patients treated for 12 weeks. No particular antibiotic (especially fluoroquinolones) was associated with a lower Shannon index or distinct dynamic of recovery at the end of treatment. PCoA analysis of the Bray Curtis distance shows that patients with elevated plasma level of CRP (≥5mg/L) at EOT had a distinct gut microbial composition compared to others. Conclusions. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery 2 weeks after antibiotic withdrawal, independently on the duration of the therapy and on the type of the antibiotic used. Elevated CRP at EOT might reflect persistent alteration of the gut microbiota. Assessment of long-term impact after the end of treatment is on-going

Prevention and treatment of total joint infection is closely related to biofilm formation and concentration of antibiotics achieved in the area around the implants. Most total joint infections are caused by bacteria that enter the wound at the time of the operation. These bacteria can attach to surfaces and rapidly form biofilm that is highly resistant to antibiotics. Prophylactic antibiotics given intravenously achieve concentration of local antibiotics in the knee in response to intravenous antibiotics about 1/3 of that achieved in the serum, and the level is transient. This may be enough to treat the planktonic form of the bacteria, but far from enough to treat the biofilm. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and cost analysis shows remarkable monetary benefit to this effect. Infected total joints benefit especially from direct application of antibiotics to the local area. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were thousands of times higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics. Preventing and treating infection in orthopaedic implant surgery requires achieving concentrations that are above the minimal biofilm eradication concentration. This can be achieved only with direct application

The burden of periprosthetic joint infection (PJI) continues to rise and the management of this dreaded complication continues to pose challenges to the orthopaedic community. Dr Buchholz from the Endo Klinik has been credited for reporting the initial observation that addition of antibiotic to polymethylmethacrylate (PMMA) cement lead to better ability to deliver higher concentrations of antibiotic to the joint milieu and avoid administration of high doses of systemic antibiotics with potential for systemic toxicity. Addition of antibiotics to PMMA cement has continued to be an important aspect of managing patients with chronic PJI. The rationale for this practice is that higher doses of local antibiotics can be reached without placing the patients at risk of systemic toxicity. Whether a one-stage or a two-stage exchange arthroplasty is being performed, antibiotics that can withstand the exothermic reaction of PMMA and are able to elude from cement are added at various doses to the PMMA for later delivery. Although this practice continues to be almost universal, there are a few unknowns. First of all, a recent study raised a valid question regarding this practice. Though intuitively logical, addition of antibiotics to PMMA spacers has not been scrutinised by any level 1 study and hence one is not able to prove that this practice does indeed accomplish its intended objectives of reducing recurrence or persistence of infection. Orthopaedic community is advised to seek avenues to generate this much-needed evidence. The other main unknown is how much, and in some instances which antibiotic, needs to be added to the PMMA cement. Some authorities have declared that antibiotics can be added at high doses, with an average total dose of 10.5 g of vancomycin (range, 3–16 g) and 12.5 g of gentamicin (range, 3.6–19.2 g) in one study, to PMMA cement without the fear of systemic toxicity. In recent years, renal toxicity and other systemic adverse effects have been attributed to addition of high doses of antibiotics to cement. I have personally witnessed such adverse reactions in a few patients. Although initially I was inclined to “blame” the concurrent administration of systemic antibiotics for the renal toxicity that patients developed following insertion of spacer, selective nephrotoxicity (i.e. reaction to aminoglycoside that was only present in the spacer and not systemically administered) and resolution of the nephrotoxicity upon removal of antibiotic spacer, convinced me that our nephrology colleagues have a valid reason to be concerned about addition of high doses of antibiotics to PMMA spacers. What has become clear is that high viscosity cements containing MA-MMA copolymers have been shown to have better antibiotic elution profiles than other PMMA formulations. So when fashioning a spacer in the operating room the surgeon needs to be aware of the differences in elution profile of antibiotics from PMMA and individualise the dose of antibiotics being added to spacer based on the type and viscosity of cement being used and the renal status of the patient. Thus, systemic toxicity caused by addition of antibiotics to cement spacer appears to be a real issue in some circumstances and this needs to be born in mind when managing patients with PJI. There are numerous other issues related to the use of antibiotic cement spacers. In the hip, the lack of adequate offset and limited portfolio of products result in laxity in the soft tissue and subsequent dislocation of the hip. In addition, the dose and type of antibiotic in the premanufactured spacers, at least in the US, are inadequate to lead to a substantial delivery of antibiotics in the local tissues. Because of these issues, I prefer to fabricate “customised” spacers for each patient that I operate on

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

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Prosthetic joint infections (PJIs) with prior multiple failed surgeries for re-infection (PMFSR) represented 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 for treatment of PJIs with PMFSR. A retrospective analysis included 78 PJIs (29 hips; 49 knees) with PMFSR, who were treated with single-stage revision using intra-articular antibiotic infusion. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, a intra-articular infusion of vancomycin, imipenem or voriconazole was performed post-operatively. The antibiotic solution was soaked into the joint for 24 hours then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Of these 78 patients, 59 had more than twice failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, 3 hips underwent a failed two-stage revision and 4 cases had a failed one-stage revision before their single-stage revision. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months. No significant difference in infection control rate was observed between hip and knee PJIs (89.7% versus 85.7%). The mean postoperative Harris hip score was 76.1 points and HSS score was 78. 2 at the most recent assessment. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid therefore overcome poor vascular supply and biofilm formation, which can be a viable option in treating PJI with PMFSR

Aims. Urinary catheter use in the peri-operative and post-operative phase following arthroplasty may be associated with increased risk of urinary tract infection (UTI) and deep prosthetic joint infection (PJI). These can be catastrophic complications in joint arthroplasty. We performed a systematic review of the evidence on routine use of antibiotics for urinary catheter insertion and removal following arthroplasty. Methods. Electronic databases were searched using the HDAS interface. Grey literature was also searched. From 219 citations, six studies were deemed eligible for review. Due to study heterogeneity a narrative approach was adopted. Methodological quality of each study was assessed using the CASP appraisal tool. Included studies were found to have moderate to good methodological quality. Results. A total of 4696 hip and knee arthroplasties were performed on 4578 participants across all studies. Of these 1475 (31%) were undertaken on men and 3189 (68%) on women. The mean age of the study participants was 69 years. 3489 cases (74.3%) related to hip arthroplasty and 629 of cases (13.4%) to knee arthroplasty. 578 cases (12.3%) specified either hip or knee arthroplasty. In total, 45 PJIs were reported across all studies (0.96%). Two of the studies found either no PJI or no statistical difference in the rate of PJI when antibiotic prophylaxis was not used for catheter manipulation. Where studies report potential haematogenous spread from UTIs, this association can only be assumed. Rates of bacteriuria varied greatly between studies and depend on timing of sample and gender. Increased duration of urinary catheterisation is positively associated with UTI. Conclusion. It remains difficult to justify the routine use of prophylactic antibiotics for catheter manipulation in well patients undergoing arthroplasty. Their use is not recommended for this indication

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

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. Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods. Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results. Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion. The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases. Cite this article: Bone Joint Res 2024;13(3):127–135

Aim. Bone and joint infections are frequent in African countries and their prevention and treatment remain a great challenge. This study aimed to determine the bacterial ecology and sensitivity of isolates to locally available antibiotics in orthopedic unit of a tertiary care hospital in Cameroun. Method. During a 12 months period, all the patients presenting with osteomyelitis or septic arthritis irrespective of the mechanism and the location were enrolled in this study. Intraoperative samples (biopsies) were taken and sent for microbiological analysis, and all strains isolated were tested for antibiotic sensitivity according to conventional methods. Results. on the 52 bacteriological analysis performed, 48 were positive. The most isolated germs were staphylococcus aureus (41.9 % of isolates), pseudomonas aeruginosa (14.5 %), Escherichia coli (14.5 %) and Klebsiella pneumonia (12.9 %). The antibiotic sensitivity pattern revealed worrying resistance rates for common and affordable antibiotics: ampicillin (94 %), amoxicillin + clavulanic acid (63.9 %), ceftazidim (65.5%), ticarcillin + clavulanate (57.4%), gentamycin (49 %), ciprofloxacin (40 %), cefuroxim (40 %), tobramycin (38.5 %). The strains of Staphylococcus aureus showed resistance to penicillin G (83%), oxacillin (25%), lincomycin (27%) and vancomycin (7%). The overall highest sensitivity rates were observed with amikacin (92 %) and imipenem (90.1%), which for many patients were the only effective locally available antibiotics. The daily cost of treatment with those two antibiotics is close to the guaranteed minimum wage in our country. Conclusions. The alarming rate of multidrug-resistant bacteria makes the long antibiotic treatment of bone infections unaffordable (in a context of lack of social insurance) for most of our patients. We advocate strong national policies for bacteriological surveillance and antibiotic misuse de-escalation to prevent antibiotic resistance

Many studies report the incidence and prevalence of surgical site infections (SSIs) following open fractures; however, there is limited information on the treatment and subsequent outcomes of superficial SSIs in open fracture patients. There is also a lack of clinical studies describing the prognostic factors that are associated with failure of antibiotic treatment (non-operative) for superficial SSI. To address this gap, we used data from the FLOW (Fluid Lavage in Open Fracture Wounds) trial to determine how successful antibiotic treatment was for superficial SSIs and to identify prognostic factors that could be predictive of antibiotic treatment failure. This is a secondary analysis of the FLOW trial dataset. The FLOW trial included 2,445 operatively managed open fracture patients. FLOW participants who had a non-operatively managed superficial SSI diagnosed in the 12 months post-fracture were included in this analysis. Participants were grouped into two categories: 1) participants whose superficial SSI resolved with antibiotics alone and 2) participants whose SSI did not resolve with antibiotics alone (defined as requiring surgical management or SSI being unresolved at final follow-up (12-months post-fracture for the FLOW trial)). Antibiotic treatment success and the date when this occurred was defined by the treating surgeon. A logistic binary regression analysis was conducted to identify factors associated with superficial SSI antibiotic success. Based on biologic rationale and previous literature, a priori we identified 13 (corresponding to 14 levels) potential factors to be included in the regression model. Superficial SSIs were diagnosed in168 participants within 12 months of their fracture. Of these, 139 (82.7%) had their superficial SSI treated with antibiotics alone. The antibiotic treatment was successful in resolving the superficial SSI in 97 participants (69.8%) and unsuccessful in resolving the SSI in 42 participants (30.2%). We found that superficial SSIs that were diagnosed later in follow-up were associated with failure of treatment with antibiotic alone (Odds ratio 1.05 for every week in diagnosis delay, 95% Confidence Interval 1.004–1.099; p=0.03). Age, sex, fracture severity, fracture pattern, wound size, time from injury to initial surgical irrigation and debridement were not associated with antibiotic treatment failure. Our secondary analysis of prospectively collected FLOW data found antibiotics alone resolved superficial SSIs in 69.8% of patients diagnosed with superficial SSIs. We also found that superficial SSIs that were diagnosed earlier in follow-up were associated with successful treatment with antibiotics alone. This suggests that if superficial SSIs are diagnosed and treated promptly, there is a higher probability that they will resolve with antibiotic treatment

Aims. Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre. Methods. A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes. Results. All patients had comorbidities and/or non-spinal procedures within the previous year. Most infections affected lumbar segments (20/32), with Escherichia coli the commonest organism (17/32). Causative organisms were identified by blood culture (23/32), biopsy/aspiration (7/32), or intraoperative samples (2/32). There were 56 different antibiotic regimes, with oral (PO) ciprofloxacin being the most prevalent (13/56; 17.6%). Multilevel, contiguous infections were common (8/32; 25%), usually resulting in bone destruction and collapse. Epidural collections were seen in 13/32 (40.6%). In total, five patients required surgery, three for neurological deterioration. Overall, 24 patients improved or recovered with a mean halving of CRP at 8.5 days (SD 6). At the time of review (two to six years post-diagnosis), 16 patients (50%) were deceased. Conclusion. This is the largest published cohort of gram-negative spinal infections. In older patients with comorbidities and/or previous interventions in the last year, a high level of suspicion must be given to gram-negative infection with blood cultures and biopsy essential. Early organism identification permits targeted treatment and good initial clinical outcomes; however, mortality is 50% in this cohort at a mean of 4.2 years (2 to 6) after diagnosis. Cite this article: Bone Jt Open 2024;5(5):435–443

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. With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). Methods. A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10. 4. colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Results. Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. Conclusion. In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49–60

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

Diabetic foot problems are a common cause for hospitalisation in this group and up to 25% of diabetic patients will be affected. Prevalence of diabetes is rising, currently affecting 680000000 people worldwide. The enormity of this problem mandates any strategy that shortens therapeutic period and enhances success rates. Cerament G has been used in our unit as a treatment adjunct in diabetic foot treatment. Successful treatment is viewed as eradication of infection and a functional foot. Retrospective review of 40 months practice with 115 patients. Inclusion: all diabetic feet requiring surgery Cerament G used, protocol driven Microbiology pathway. Exclusion: Primary closure not possible. Cerament G not used. Outcome assessed in three groups: Total failure (further surgery required); slow to heal (healing by secondary intention); healed without problems. Healed 99 (eradication of infection and return to function), failure to heal 16 (success rate: 86.1%). Infection was the cause of failure in only in 2.6% (13 failures due to patient noncompliance or poor vascularity). Accepted success rate in treating osteomyelitis in diabetic feet is 68% (medical treatment only), combination of surgery and medical is 86%. Eradication of infection is the only end point return to function is not addressed. This study shows Cerament G with surgery/systemic antibiotics provides a 97.4% success rate. Therapeutic drivers in this field have been determined traditionally by Physicians and Vascular Surgeons (resection rather than reconstructive surgery.) Our assertion is that eradicating infection in a functionally useless foot is a waste of health resources. Our strategy is always the delivery of an intact functional foot residuum. Cerament G as an adjunct allows this goal in a cost-effective manner

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

Aim. Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone of perioperative pain management in orthopedic trauma surgery, although concerns persist regarding the potential impact of these drugs on fracture healing. Furthermore, NSAIDs may also exert an influence on host immune defenses, which may also be important in the context of infection treatment. However, this has been very much under-investigated in the clinical and scientific literature. The aim of this study was to determine the impact of NSAIDs on the course of an orthopedic device-related infection (ODRI) and its response to antibiotic therapy in a rat model. Method. A polyetheretherketone (PEEK) screw was inserted in the proximal tibia of 48 skeletally mature female Wistar rats: 12 control animals received a sterile screw, of which 6 also received NSAID therapy (carprofen, 5 mg/kg s.c. once daily); 36 rats received a Staphylococcus epidermidis-inoculated screw, of which 18 received NSAID therapy. Antibiotic therapy was administered from day 7–21 in 9 animals from all groups receiving S. epidermidis-inoculated screws (cefazolin: 30 mg/kg; s.c., b.i.d. plus rifampin: 25 mg/kg; s.c., b.i.d.). Bone histomorphometric changes were monitored using longitudinal microCT scanning, performed postoperatively, and at 3, 6, 9, 14, 20 and 28 days (euthanasia). Quantitative bacteriology of the implant, bone and overlying soft tissue was performed to assess infection status of individual animals. Results. All animals receiving S. epidermidis-inoculated screws in the absence of antibiotic therapy were confirmed as infected at euthanasia. Quantitative microbiology showed no significant change in bacterial load in NSAID-treated animals versus control. However, NSAID administration dramatically impaired antibiotic efficacy, with 7/8 animals remaining infected when NSAIDs were co-administered, whilst only 2/9 of control animals were infected when NSAIDs were withheld. Pronounced osteolysis was observed by day 6–9 in control animals, with reparative processes (periosteal proliferation and mineralization) observed at day 14. NSAID treatment markedly prevented S. epidermidis-induced osteolysis, but also reparative processes. Antibiotic treatment did not affect the bone changes. Conclusions. NSAID administration dramatically affected the response of bone tissue to infection, reducing osteolysis but also impairing reparative processes. Crucially, NSAIDs dramatically reduced antibiotic efficacy. Given these pronounced negative effects, further investigations should be conducted to determine the underlying pathophysiological mechanism and better understand the consequences of the therapeutic use of NSAIDs in human patients with ODRI

Aim. Local concentration of antibiotic at the site of infection is a major parameter for its efficiency. However, bone diffusion is poor leading either to their non-use (ex: gentamicin) or the use of high concentration (ex: vancomycin). Local administration could optimize their local concentration combined with lower side effects. We report the clinical experience and pharmacological results of an antibiotic loaded porous alumina used to replace infected bone in 4 patients. Method. Two patients had a destroyed sternum following mediastinitis; one presented a femoral chronic osteomyelitis due to MRSA and one had an infected ankle arthroplasty. The ceramic was loaded with gentamicin in three cases and vancomycin for the ankle infection. Local dosages thanks to Redon's drain and blood samples were performed. Loading was done to protect the device while implanted in an infected area and was combined with conventional antibiotic therapy. Results. In comparison to pharmacological parameters: C. max. /MIC>8 for gentamicin or AUC/MIC>400 for vancomycin, local concentrations were dramatically higher than the one needed (table). Vancomycin concentration was still high after H48. Meanwhile, blood samples didn't find the presence of gentamicin during the 48 hours following implantation. After more than one year of follow-up for all the patients, there is no relapse of infection or signs of device infection, whereas all samples perform during implantations grew with bacteria, meaning that loaded antibiotic played a major role avoiding device colonization in combination with surgical debridement and cleaning. Conclusions. This mode of administration allows an optimization of the antibiotic delivery, maximizing local concentrations while reducing systemic toxicity. In addition, ceramic mechanical characteristics allow bone replacement (strength >3 times the one of the cancellous bone and osseointegration) and thus enables one-stage surgery instead of two-stage like for the patient with chronic osteomyelitis thanks to a good primary stability. For any figures or tables, please contact the authors directly

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

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalization, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intraarticular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included débridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 µg/mL. Mean serum vancomycin peak concentration was 6 ± 2 µg/mL and the mean serum vancomycin trough concentration was 3 ± 1 µg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 µg/mL and 20,167 µg/mL and trough concentrations were 724 µg/mL and 543 µg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean followup was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83 ± 9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

Objective. Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. . Methods. We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. . Results. We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. . Conclusions. It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162

Aim. Irrigation is a major step during debridement surgery in the context of Prosthetic Joint Infections (PJI), but its effects on biofilms are poorly described. The present study aims at evaluating the effect of PW alone or followed by antibiotics on MSSA and MRSA biofilms grown on Ti6Al4V coupons in-vitro. Method. Strains: 1 reference (MSSA: ATCC25923; MRSA: ATCC33591) and 2 clinical MSSA and MRSA isolated from PJI. Biofilm culture: Coupons were incubated for 24h at 37°C with bacteria (starting inoculum ∼6.6Log. 10. CFU/mL in TGN [TSB + 1% glucose + 2% NaCl]), under shaking at 50rpm. Treatment: Half of the coupons were irrigated with 50mL physiological serum from 5cm using a Stryker Interpulse; the coupons were then either analysed (ControlT0 and PWT0) or reincubated for 24h in TGN or TGN containing flucloxacillin (MSSA) or vancomycin (MRSA) at MIC or 20mg/L. Analysis: Coupons were rinsed twice with PBS. Biomass was measured by crystal violet (CV) assay. CFUs were counted after recovering bacteria from coupons using sonication and TSA plating. Results. Antibiotics alone: Flucloxacillin reduced CFU and biomass for ATCC25923 and 611 but not 578 (Fig b and d). Vancomycin had no statistically significant effects on CFUs for all MRSA and only a weak effect on biomass for 676. Irrigation alone markedly reduced CFUs and biomass for all strains but had no persistent effect after 24h reincubation in TGN. PW + antibiotics: Antibiotics prevented bacterial regrowth after PW when used at their MIC and further decreased CFUs when used at 20 mg/L. Conclusions. PW alone has a transient effect on coupon colonisation by S. aureus biofilms. Vancomycin at therapeutic concentrations is ineffective and flucloxacillin has a strain-dependent effect. In combination, these treatments show synergistic effects, indicating the importance of irrigation followed by high antibiotic doses for ODRI. For any figures or tables, please contact the authors directly

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

Aim. Patients use antibiotics for various reasons before elective joint replacement surgery, but it is not known how common this is. The aim of this study was to investigate patients' use of oral antibiotics before elective joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI) in a one-year follow-up. Method. Patients with a primary hip or knee replacement performed in a tertiary care hospital between September 2002 and December 2013 were identified (23 171 joint replacements, 10 200 hips and 12 971 knees). Information on oral antibiotics purchased within 90 days before the operation was gathered from a national database. The occurrence of a PJI, identified by prospective infection surveillance, in a one-year follow-up was the primary outcome. The occurrence of any surgical site infection was analyzed as a secondary outcome. The association between antibiotic use and subsequent infection was examined using a multivariable logistic regression model that included information on the operated joint, age, gender, body mass index and patients' chronic diseases (according to medication data). Results. During the one-year follow-up, 158 (0.68%) PJIs were identified. 4 106 (18%) of the joint replacement operations were preceded by one or more courses of oral antibiotics. The most commonly prescribed group of antibiotics was 1st generation cephalosporins. The incidence of PJI for patients with preoperative oral antibiotic use was 0.29% (12/4 106), compared to 0.77% (146/19 065) in patients without preoperative antibiotics. A preoperative oral antibiotic course decreased the risk for subsequent PJI both in the univariate (OR 0.38, 95% CI 0.21 – 0.69) and multivariable model (OR 0.40, 95% CI 0.22–0.73). When superficial infection cases were included in the analysis, preoperative antibiotic use did not affect the overall risk for surgical site infection. Conclusions. The use of oral antibiotics before elective joint replacement surgery is common and is associated with a lower risk for subsequent PJI. Further studies are needed in order to confirm this finding and to evaluate factors affecting this result. Meanwhile, the indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though the treatment of active infections remains important in the prevention of surgical site infections

Objectives. We wanted to investigate regional variations in the organisms reported to be causing peri-prosthetic infections and to report on prophylaxis regimens currently in use across England. Methods. Analysis of data routinely collected by Public Health England’s (PHE) national surgical site infection database on elective primary hip and knee arthroplasty procedures between April 2010 and March 2013 to investigate regional variations in causative organisms. A separate national survey of 145 hospital Trusts (groups of hospitals under local management) in England routinely performing primary hip and/or knee arthroplasty was carried out by standard email questionnaire. Results. Analysis of 189 858 elective primary hip and knee arthroplasty procedures and 1116 surgical site infections found statistically significant variations for some causative organism between regions. There was a 100% response rate to the prophylaxis questionnaire that showed substantial variation between individual trust guidelines. A number of regimens currently in use are inconsistent with the best available evidence. Conclusions. The approach towards antibiotic prophylaxis in elective arthroplasty nationwide reveals substantial variation without clear justification. Only seven causative organisms are responsible for 89% of infections affecting primary hip and knee arthroplasty, which cannot justify such widespread variation between prophylactic antibiotic policies. Cite this article: Bone Joint Res 2015;4:181–189

Introduction. Periprosthetic infection (PJI) after primary total knee arthroplasty (TKA) remains a challenging issue affecting 1–2% of cases. Locally delivered prophylactic antibiotics, including tobramycin or gentamicin mixed in polymethylmethacrylate (PMMA) bone cement and vancomycin powder, are increasingly used despite a lack of high quality evidence for either practice. In this study, we report the antibiotic susceptibility of organisms recovered in culture from patients with acute prosthetic joint infection after primary TKA to gentamicin, tobramycin and vancomycin. Methods. Using a retrospective database of all primary TKA performed at a single institution between January, 1 2014 and July 1, 2018, we identified 18 cases of acute PJI after primary TKA, as defined by the Musculoskeletal Infection Society 2011 guidelines as less than 3 months from symptoms or index surgery to presentation. The use of antibiotic bone cement during the index procedure and time to surgical management of the infection were recorded. Fluid cultures and tissue cultures were obtained intraoperatively at the time of revision. The organisms from positive cultures underwent MIC testing to gentamicin, tobramycin and vancomycin using a gradient diffusion method (ETEST). MIC breakpoints for susceptibility were based on Clinical and Laboratory Standards Institute definitions. Results. 18 cases of PJI after TKA were identified, including 4 polymicrobial infections (22.2%) (Table 1). Average time to revision for infection was 38 days (range: 6–84 days). 34.8% of bacterial isolates were resistant to gentamicin, 39.1% were resistant to tobramycin and 17.4% were resistant to vancomycin. Of the 8 bacterial isolates resistant to gentamicin, 7 (87.5%) were susceptible tobramycin. Of the 9 bacterial isolates resistant to tobramycin, (88.9%) were susceptible to vancomycin. One bacterial isolate, a Fusobacterium nucleatum from a polymicrobial infection was resistant to gentamicin, tobramycin and vancomycin. Conclusion. Over one third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides pre-mixed in commercially available bone cements. All but one of the bacteria resistant to gentamicin and tobramycin were susceptible to vancomycin. The addition of vancomycin to bone cement or as powder in the surgical field has the potential to expand antibiotic coverage to include most organisms responsible for acute PJI after TKA. For figures, tables, or references, please contact authors directly

The February 2024 Trauma Roundup. 360. looks at: Posterior malleolus fractures: what about medium-sized fragments?; Acute or delayed total hip arthroplasty after acetabular fracture fixation?; Intrawound antibiotics reduce the risk of deep infections in fracture fixation; Does the VANCO trial represent real world patients?; Can a restrictive transfusion protocol be effective beyond initial resuscitation?; What risk factors result in avascular necrosis of the talus?; Pre-existing anxiety and mood disorders have a role to play in complex regional pain syndrome; Three- and four-part proximal humeral fractures at ten years

The August 2023 Hip & Pelvis Roundup. 360. looks at: Using machine learning to predict venous thromboembolism and major bleeding events following total joint arthroplasty; Antibiotic length in revision total hip arthroplasty; Preoperative colonization and worse outcomes; Short stem cemented total hip arthroplasty; What are the outcomes of one- versus two-stage revisions in the UK?; To cement or not to cement? The best approach in hemiarthroplasty; Similar re-revisions in cemented and cementless femoral revisions for periprosthetic femoral fractures in total hip arthroplasty; Are hip precautions still needed?

Aim. Antibiotic-eluting calcium compounds can be used to deliver antibiotics in the management of prosthetic joint infection (PJI). Described omplications include wound drainage, heterotopic ossification(HO) as well as hypercalcaemia which is potentially life threatening. The aim of this study is to assess the incidence of hypercalcaemia and other complications between two calcium based antibiotic delivery systems. Method. A retrospective study was performed. Thirty two patients treated with Stimulan or Cerament Calcium based antibiotic delivery system between August 2014 to January 2017 were included. Seven patients received Cerament, 21 cases received Stimulan and one patient received both. The volume used as well as pre- and post-operative serum calcium were recorded as well as any wound related complications and radiologic changes suggestive of heterotopic ossification. The postoperative serum adjusted Calcium were taken weekly during the initial post operative period. Patients with overactive parathyroid disease and pre-existing renal disease were excluded. Results. Stimulan group (n=22, Mean volume 39.2ml). Mean pre-operative serum calcium was 2.48mmol/l. At 1 and 2 weeks post-surgery mean levels were 2.51 and 2.47mmol/l (patients receiving <40ml), and 2.47 and 2.50mmol/l (patients receiving >40ml – 9 cases) respectively. There was no significant difference between pre/post-operative levels at 1 (p=0.97) or 2 weeks (p=0.91) and no difference between those treated with <40ml or >40ml of Stimulan at 1 or 2 weeks (p=0.91). Cerament group (n=8, Mean volume 9.4ml). Mean pre-operative serum calcium was 2.42mmol/l. Mean post-operative levels at 1 and 2 weeks post-surgery were 2.44mmol/l (p=0.92) and 2.37mmol/l (p=0.61) respectively. One patient had prolonged wound discharge and required re operation. No HO was encountered. Conclusions. Our results suggest that hypercalcaemia and other complications are uncommon with the use calcium based antibiotic delivery systems and that calcium based antibiotic delivery systems are safe in the treatment of PJI

Aim. Antibiotic loaded spacers are often used during a two-stage exchange for periprosthetic joint infections (PJI) both for its mechanical properties and as a means for local antibiotic delivery. The main goal of this study is to compare the rate of positive cultures during reimplantation with the use of different antibiotic loaded spacers: aminoglycoside only vs. combined glycopeptide/aminoglycoside vs. combined glycopeptide/carbapenem/aminoglycoside. Method. We retrospectively evaluated every two-stage exchange procedures for infected hip/knee arthroplasty between 2012–2018. Microbiological findings in the first and second stage were registered as well as the type of spacer and antibiotic(s) used. Cases in whom no cultures were obtained during reimplantation and cases without sufficient data on antibiotic(s) used in cement spacers were excluded. Results. Fifty-four cases were included (20THA and 34TKA), with an overall rate of positive cultures during reimplantation of 18.5% (10/54). The rate of positive cultures was statistically significant higher among spacers with monotherapy with aminoglycoside compared to spacers with combined antibiotic therapy- 35.7% (5/14) vs. 12.5% (5/40) respectively(p<0.05). Comparing those with combined glycopeptide/aminoglycoside (2/19) with triple glycopeptide/carbapenem/aminoglycoside therapy (3/21) there was no significant difference. Microorganisms present during the second stage were mostly staphylococci (coagulase-negative in four cases, S.aureus in three), Corynebacterium striatum, Enterococcus faecalis, C.albicans in one case each. In most cases (8/10), the isolated microorganism was the same as the first stage and was resistant to the antibiotic(s) used in the spacer in seven cases. Failure rate with the need for subsequent surgery was significantly higher at 60% (6/10) in cases with positive cultures at reimplantation compared to 4.5% (2/44) for those with negative cultures during reimplantation(p=0.0005). Conclusions. It has recently been suggested that adding a glycopeptide to the spacer may be advantageous when compared to spacers with aminoglycoside monotherapy, as it will produce significantly lower rates of positive cultures during reimplantation which have been shown to increase the risk of subsequent failure as is the case in our study. Local unavailability of obtaining powder aminoglycosides has driven us to manually add high doses of vancomycin and meropenem to commercially available low-dose gentamicin cement in many of our spacers and they seem to to perform just as well as commercially available vancomycin/gentamicin combination. Although many other variables not considered in this study may influence the rate of positive cultures during the second stage (quality of initial debridement, systemic antibiotic therapy, etc.), we believe these results portrait a sufficiently accurate picture of clinical results with the use of different spacers

The management of periprosthetic joint infection is challenging and the duration of systemic antibiotic therapy whether it be during the interval phase or after reimplantation of a new prosthesis is controversial. We report our experience of managing chronic periprosthetic infection of the hip by the two stage exchange procedure. Patients who were scheduled to undergo a two stage revision for chronic periprosthetic infection of the hip were identified from our prospective database. Of 425 patients with microbiologically proven periprosthetic infection, 369 (87%) underwent a two stage procedure, leaving 56 patients who did not proceed to reimplantation. 41 of these were clinically infection free but for personal or medical reasons did not proceed. The remaining 15 had persistent infection. The mean age at the time of the first stage was 68 years (26 – 92 yrs). 256 (61%) patients were alive for review. The mean time between stages was 6.3 months with a mean follow up after the second stage was 65 months (range 5 to 276 months). The success rate of a single 1. st. stage debridement, confirmed by negative cultures at the time of second stage reimplantation was 94%. 19 patients underwent a repeat 1. st. stage debridement and were classed as failures of the 1. st. stage. At the time of final review, 340 (92%) patients were deemed infection free out of those who had completed a 2 stage exchange. The duration of systemic antibiotic treatment after both the 1. st. and 2. nd. stages was divided into <48 hrs and >48 hours. There was no significant difference in the success of the 1. st. stage procedure in patients who received < 48 hours (48% of the patients) as opposed to > 48 hours (p = 0.98, Chi Squared Test, Relative Risk 1.009). Similarly there was no difference in the overall success of the two stage procedure irrespective of the duration of antibiotic therapy with 76% of patients receiving <48hrs of antibiotics after the second stage. Aggressive surgical debridement together with targeted local and short term systemic antibiotic therapy should be the mainstay of treatment in two stage revision surgery

There is high morbidity and mortality associated with infection following orthopaedic procedures. In accordance to local guidelines, most hospitals follow a set protocol for surgical prophylaxis, which expects a compliance rate of 100%. A new protocol was introduced to the orthopaedic department of a teaching hospital in August 2013, changing from a cephalosporin, with potential C. difficile risk, to teicoplanin and gentamicin, within 30 minutes of incision. Our aim was to audit how well the protocol was followed across 3 different time periods. Data was collected for 3 different time periods following the introduction of the new protocol (August-November 2013, April-May 2014 & November 2014) on the choice of antibiotic. Both elective and trauma cases were included. After each cycle, the data was presented to the orthopaedic surgical and anaesthetic departments to raise awareness and draw attention to the antibiotic prophylaxis posters in theatre. The 1st audit cycle (n=30) indicated that there was 0% compliance with the current protocol and 100% compliance with the previous protocol. The 2nd audit cycle (n=27) indicated that 0% complied with the current protocol, 54% complied with the previous protocol and that there was a combination of both protocols being used in 46% of the patients. Finally the 3rd audit cycle (n=33) indicated a 100% compliance rate in terms of antibiotic choice. However, only 9% were given the appropriate dose according to body weight and within the appropriate time based on the documented evidence. This audit demonstrates the value of auditing and then disseminating the findings to relevant departments to influence practice. Each audit cycle demonstrated a progressive uptake in compliance with the hospital trust's antibiotic prophylaxis policy. The last audit cycle highlighted discrepancy in dosage based on weights; a further intervention will be to provide ideal body weight (IBW) vs dose tables in all orthopaedic theatres to ensure the correct antibiotic dosage is given

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

The April 2024 Research Roundup. 360. looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth hormone therapy and proximal tibial physeal avulsion fractures in children and adolescents; UK pregnancy in orthopaedics (UK-POP): a cross-sectional study of UK female trauma and orthopaedic surgeons and their experiences of pregnancy; Does preoperative weight loss change the risk of adverse outcomes in total knee arthroplasty by initial BMI classification?

Aim. The optimal treatment of displaced intra-articular calcaneal fractures (DIACF) remains controversial. The operative treatment group has better anatomical recovery, functional outcome scores and less pain than non operative treatment patients, but it may lead to a higher incidence of complications, such as delayed wound healing and surgical site infections. The aim of this study was to analyze the prophylactic effect using a biphasic bone substitute (BS) eluting antibiotic on calcaneal implant-related infections. Methods. We conducted a retrospective non-randomized review of all patients with DIACF (type Sanders 2, 3, 4) from 2009 to 2017; 103 calcaneal fractures of 90 patients (13 bilaterally) were treated with plates. All cases received the same systemic antibiotic prophylaxis; BS was used on more complex cases with large bone defect and BS was added with antibiotic on higher risk patients. We collected data including complications: major (deep infections, osteomyelitis) and minor complications (wound dehiscence, superficial infection). We considered the absence of deep infections after 6 months. We compared statistically the outcomes of 3 operative groups: the first was treated with plates only (A), the second with plates and BS (B) and the third with plates added with BS eluting antibiotic (vancomicine or gentamicine) (C). Results. We examined 99 cases (group A: n33, B: n52, C: n14), 4 patients were lost; the mean age was 47,8 years (range 18–83 years). Minimal follow up was 6 months (range: 6 – 42 months). We have observed 8 (8,1%) implant-related infection (A:4, 12,1%; B:4, 7,7%), 2 (2%) superficial infection (B:2, 3,8%), 20 (20,2%) wound healing defects (A:11, 33,3%; B:7, 13,5%; C:2, 14,2%). We found a relevant reduction of the rates in the group C regarding the major complications without a statistic evidence. Conclusion. The three groups are uneven; particularly the group C has a high concentration of more severe risk patients. The low number of cases in the group C, which limited the statistic evidence, represents a second limit. The absence of major infection on group C found in this study, needs larger data to confirm this result. The open surgery has an intrinsic rate of skin complications but the use of BS eluting local antibiotic is an additional tool to manage difficult complex fractures and to prevent implanted-related infection, inhibiting bacterial colonization and biofilm protection, particularly in those patients that have suffered from a minor complication, which could lead to a deep infection

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