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. 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. 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. This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results. AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion. The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management. Cite this article: Bone Joint Res 2024;13(10):525–534

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. 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. 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. 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

Aim. The SOLARIO trial is a randomised controlled non-inferiority trial of antibiotic strategy for bone and joint infection. SOLARIO compares short or long post-operative systemic antibiotic duration, for patients with confirmed infections, who had local antibiotics implanted and no infected metalwork retained when undergoing surgery. This analysis compared systemic antibiotic use in the short (intervention) and long (standard of care) arms of the trial, in the 12 months after index surgery. Method. Data was collected prospectively from study randomisation, within 7 days of index surgery. All systemic antibiotics prescribed for the index infection were recorded, from health records and patient recall, at randomisation, 6 weeks, 3-6 months and 12 months after study entry. Start and end dates for each antibiotic were recorded. Results. 251 patients were randomised to short systemic antibiotics (up to 7 post-operative days) and 249 patients, to long systemic antibiotics. 5 participants in the short group and 2 participants in the long group withdrew from study follow-up. Complete data for all systemic antibiotics taken in the 12 months following surgery, were available for 237 participants in the short group and 236 participants in the long group. 80 participants across both groups were noted as having deviated from their assigned treatment strategy. Both groups received empiric antibiotics, predominantly vancomycin and meropenem, for up to 7 days after surgery. Considering each prescribed antibiotic as a separate duration (even when administered concurrently), participants assigned to standard care received a mean of 74.9 antibiotic-days. Participants assigned to short systemic antibiotics received a mean of 27.5 antibiotic-days in the 12 months after surgery. The most commonly prescribed antibiotics in both treatment groups were vancomycin and meropenem: these antibiotics accounted for 7.1 days prescribed per participant in the long group, and 6.3 days in the short group (p=0.37). Reasons for post-randomisation antibiotic prescribing in the short treatment group included later planned surgery, identification of bacteria requiring additional systemic antibiotics, and treatment of superficial wound infections. WHO AWaRe classification ‘watch’ and ‘reserve’ group antibiotics, such as ciprofloxacin, rifampicin, vancomycin and meropenem, accounted for 39.4 antibiotic-days per long group participant, and 16.5 antibiotic-days per short group participant. Conclusions. Considering the combined duration of all systemic antibiotics prescribed over 12 months, including those co-administered, participants in the short arm of the SOLARIO trial received considerably fewer days of all antibiotic classes, and particularly those antibiotics restricted in the WHO AWaRe classification (2021)

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

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

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

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

Abstract. Background. The aim of the present experimental study was to analyse vancomycin elution kinetics of nine bone fillers used in orthopaedic and trauma surgery over 42 consecutive days. Methods. Two allograft bone chips (carriers 1 and 2), a calcium-sulfate matrix (carrier 3), a hydroxyapatite/calcium-sulphate composite (carrier 4), four bone cements (carriers 5-8) and a pure tricalcium phosphate matrix (carrier 9), either already contained vancomycin, or were mixed with it following manufacturer's recommendations. Over 42 days, half of elution medium was substituted by the same amount of PBS at 9 distinct time points. Vancomycin concentration in obtained samples were measured with a kinetic microparticle immunoassay, and masses consecutively calculated. To enhance comparability between carriers analysed, vancomycin mass released related to overall mass within each probe was determined. Notably, elution kinetics of carriers 1 to 4 have been published previously. Results. All carriers initially released high vancomycin masses, followed by constant reduction later into the experiment. Mean initial vancomycin masses released after 4 hours were highest for carriers 1 (337.7 ± 76.2 mg), 9 (68.4 ± 4.9 mg), and 2 (49.0 ± 54.6 mg). From prefinal (35 days) to last measurement (42 days) carriers 2 (8.6 ± 4.8 mg), 1 (2.4 ± 1.0 mg), and 5 (0.1 ± 0.1 mg) had released highest vancomycin masses. Notably, all five bone cements tested only released a small percental amount of their total mass up to the last measurement (42 days; 2.1% – 9.3%), whilst allografts and resorbable synthetic bone fillers discarded high percental values (22.5% – 79.2%). Conclusions. Elution kinetics differ between 9 antibiotic-loaded bone fillers, with high vancomycin masses released by allografts and resorbable bone fillers over time. Transferred to clinical practice, these may be favoured over bone cements in case prolonged and high antibiotic release is warranted rather than mechanical stability

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

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

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

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