Aim. Patients reporting penicillin allergy do often receive clindamycin as systemic antibiotic prophylaxis. The effect of clindamycin has however not been compared to antibiotics with proven effect in joint arthroplasty surgery. The aim of the study was to reveal if there were differences in the rate of revision due to infection after total knee arthroplasty (TKA) depending on which antibiotic was used as systemic prophylaxis. Method. Patients reported to the Swedish Knee Arthroplasty Register having a TKA performed due to osteoarthritis (OA) during the years 2009 – 2015 were included in the study. The type of prophylactic antibiotic is individually registered. For 80,018 operations survival statistics were used to calculate the rate of revision due to infection until the end of 2015, comparing the group of patients receiving the beta-lactam cloxacillin with those receiving clindamycin as systemic prophylaxis. Results. Cloxacillin was used in 90% of the cases, clindamycin in 7% and cephalosporins in 2%. The risk of becoming revised due to infection was higher when using clindamycin than cloxacillin, RR 1.51 (95% CI: 1.18–1.95, p=0.001). There was no significant difference in revision rate due to other causes, (p=0.21). Conclusions. We advise that patients reporting allergic reaction to penicillin have their allergic history explored. In the absence of clear history of type 1 allergic reaction we suggest the use of a cephalosporin instead of clindamycin as a perioperative prophylaxis when undergoing a TKR. No recommendation can be given regarding patients with type 1 allergy

Background. North America is facing a rising epidemic involving strains of methicillin-resistant Staphylococcus aureus (MRSA) that, instead of being found almost exclusively in hospitals, are community-associated (CA-MRSA). These strains are aggressive, associated with musculoskeletal manifestations including osteomyelitis (OM), and septic arthritis (SA). We aimed to establish novel management algorithms for acute OM and SA in children. We investigated S.aureus susceptibilities to current first-line antimicrobials to determine their local efficacy. Methods. The project was conducted at Nemours Children Hospital in Florida, USA, following approval by the internal review board. A literature review was conducted. An audit of S.aureus antimicrobial sensitivities was completed over three years and compared against national standards. Susceptibilities of clindamycin, trimethoprim/sulfamethoxazole (TMP/SMX) and vancomycin were studied using local resistance ranges. Results. Two algorithms for acute OM and SA management were created adopting a multidisciplinary team approach from admission to discharge whilst differentiating higher risk patients within fast-track pathways. We analysed 532 microbiology results for antibiotic susceptibilities from 2012 to 2014. Overall, 51% of S.aureus infections were MRSA versus 49% methicillin-susceptible S.aureus (MSSA). Surprisingly, clindamycin resistance rates rose compared to 2005 (MRSA 7% in 2005 vs 39% currently, MSSA 20% vs 31% and total S.aureus resistance rate of 8% vs 35%, respectively). MRSA and MSSA isolates were near 100% sensitive to Vancomycin and TMP/SMX. No appropriate national standards existed. Conclusions. Multidisciplinary based algorithms were created for acute OM and SA treatment in children. Possible therapeutic roles for ultrasound guided aspiration and corticosteroids were highlighted in SA. Our audit revealed equal incidence of MSSA to MRSA, supporting national figures on falling MRSA. Interestingly, incresed resistance of MSSA and MRSA was found towards recommended first line clindamycin, raising concern over its efficacy. Level of Evidence. 5

Aims. Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP. Methods. This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI. Results. In all, 10,484 knees (90.8%) received cefazolin, while 1,066 knees (9.2%) received a non-cephalosporin agent (either vancomycin or clindamycin) as preoperative prophylaxis. The rate of PJI in the cefazolin group (0.5%; 48/10,484) was significantly lower than the rate of PJI in the non-cephalosporin group (1.0%; 11/1,066) (p = 0.012). After controlling for confounding variables, the odds ratio (OR) of developing a PJI was increased in the non-cephalosporin cohort compared to the cefazolin cohort (OR 2.389; 1.2 to 4.6); p = 0.01). Conclusion. Despite the use of topical irrigant solutions and addition of local antimicrobial agents, the use of a non-cephalosporin perioperative antibiotic continues to be associated with a greater risk of TKA PJI compared to cefazolin. Strategies that increase the proportion of patients receiving cefazolin rather than non-cephalosporin alternatives must be emphasized. Cite this article: Bone Jt Open 2022;3(1):35–41

Background. Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods. In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with DAIR or one-stage revision surgery between January 1. st. , 2015 and November 3. rd. , 2020, were included. Patients were treated according to a predefined protocol for PJI. Antimicrobial treatment strategies differed between centers, which was accepted and used as pseudorandomization. Depending on the hospital patients were admitted to, they were treated with either a long-term rifampicin strategy (consisting of 12 weeks rifampicin combination therapy) ore one of several short-term rifampicin strategies, consisting of only five days of rifampicin combination treatment, started immediately postoperative, followed by clindamycin, flucloxacillin or vancomycin monotherapy. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results. Two hundred patients were included and, based on the antimicrobial treatment, stratified in one long-term rifampicin group (n=23) or one of the three short-term rifampicin groups: clindamycin (n=56), flucloxacillin (n=47), vancomycin (n=26), other (n=48). Outcome of PJI after DAIR or one-stage exchange was not statistically different between patients treated with long-term rifampicin combination therapy and patients treated with clindamycin or flucloxacillin monotherapy including only five days of rifampicin combination therapy. Moreover, treatment duration was four weeks shorter in the clindamycin-based and flucloxacillin-based groups. Adjusted hazard ratios for failure for patients treated with either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR 1.21, 95%CI 0.34–4.40). Conclusions. A short-term rifampicin strategy with either clindamycin or flucloxacillin and only five days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI

Aim. There is a lack of data supporting the use of doxycycline as a single agent after removing infected orthopaedic metalwork. We evaluated the efficacy and safety of doxycycline compared with other single antibiotic regimens used at our specialist orthopaedic hospital. Methods. A retrospective observational study including all adult patients diagnosed with an orthopaedic metalwork infection due to staphylococci. All patients were managed with the removal of metalwork, and multiple intraoperative samples were sent for culture, followed by the administration of at least four weeks of oral antibiotics. Antibiotic selection was on the recommendation of an infection consultant. Infection outcome was assessed as the proportion of patients meeting the OVIVA Trial definition of definite failure at follow-up. The probability of definite failure for doxycycline and the alternatives group was estimated using the Kaplan-Meier survival method. All adverse drug reactions (ADR) during treatment were analysed. Results. Seventy-nine orthopaedic metalwork infections were identified between July 2017 and July 2021. Forty-four were prosthetic joints, and 35 were fracture-related metalwork. In 54 cases, the infecting organism was Staphylococcus aureus, and 25 were due to coagulase-negative staphylococci. Forty-four were treated with doxycycline 100mg 12 hourly, and 35 were treated with alternatives (flucloxacillin 1g 6-hourly n=21 and clindamycin 450mg 6-hourly n=14). Overall, 70 patients (88.6%) were infection-free after a median follow-up of 23 months (IQR, 19 – 44). 38 (82.3%) were infection-free in the doxycycline group compared with 32 (91.4%) patients treated with alternatives. Of the failures in the alternatives group, all 3 received flucloxacillin. Survival analysis showed no significant difference in time to treatment failure between doxycycline and alternative antibiotics. Eighteen patients experienced an ADR: 2 nausea, one rash and one vaginal candidiasis due to doxycycline. Four diarrhoea, one reflux, two rashes and one headache due to clindamycin; 1 nausea and five diarrhoea due to flucloxacillin. Four patients required discontinuation therapy, two due to clindamycin and two due to flucloxacillin. Conclusions. In our cohort of patients, doxycycline monotherapy was an effective and well-tolerated oral option for treating staphylococcal infection following debridement and removal of orthopaedic metalwork

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

Background. Although described as a commensal bacterium with low pathogenicity, Cutibacterium acnes involvement has been reported in many clinical entities: infections associated with devices, such as shoulder prosthetic joint infections, osteosynthesis, breast implants or cerebrospinal fluid shunts. Various studies show that C. acnes grows as a biofilm, contributing to its persistence by allowing its escape from the action of the immune system and antibiotics. Purpose. Our aim was to assess the activity of different active substances (erythromycin, clindamycin, doxycycline and Myrtacine. ®. ) on eight different well-characterized C. acnes strains after growth in biofilm mode. Methods. Eight susceptible strains of C. acnes were selected for this study, including two reference strains (ATCC6919 and ATCC11827) and six clinical strains. All C. acnes strains were studied using two different methods to study the biofilm production at different time points: the BioFilm Ring Test. ®. technique (early stages of adhesion) and the Crystal Violet (CV) method (mature biofilm). In a second step, the impact of different active substances (erythromycin, clindamycin, doxycycline and Myrtacine. ®. ) was studied. For the CV technique, two types of tests were performed: preventive tests (addition of active substances and bacteria at the same time) and curative challenge tests (addition of active substances on a biofilm already formed after 48h). Transmission electron microscopy was performed to investigate the morphology modifications. Results. C. acnes isolates from phylotypes IA. 1. and IA. 2. , seem to produce more mature biofilm in the first stages of adhesion than other phylotypes. Curative assays were performed to evaluate the efficacy of antibiotics and Myrtacine. ®. on mature biofilm. Significant efficacy of Myrtacine. ®. at 0.03% was observed for C. acnes strains. Moreover, the combination of Myrtacine. ®. and doxycycline appears to decrease the total biofilm biomass. The effect of doxycycline as a preventive measure was minimal. On the contrary, a similar use of Myrtacine. ®. as early as 0.001% showed significant efficacy with a significant decrease in total biofilm biomass for all C. acnes strains. Transmission electron microscopy revealed a significantly decreased biofilm growth in treated bacteria with Myrtacine. ®. compared to untreated bacteria. Moreover, the total number of bacteria decreased as the concentration of Myrtacine. ®. increased suggesting also an antimicrobial effect. Conclusion. These results confirm the difference in biofilm producing ability depending on C. acnes phylotypes. These results suggest that Myrtacine. ®. may be a promising alternative antibacterial and anti-biofilm agent like peroxide de benzoyle to prevent shoulder prosthetic joint infection involving planktonic and biofilm C. acnes

Aim. Aim was to compare revision rates when using single versus dual antibiotic loaded cement (ABLC) in hip fracture arthroplasty and aseptic revision hip or knee arthroplasty using data from the Dutch national joint registry (LROI). Methods. All primary cemented (hemi-)arthroplasties for acute hip fractures and cemented aseptic hip or knee revision arthroplasties, were incorporated in 3 datasets. All registered implants between 2007 and 2018 were included (minimum 2 years follow-up). Primary end-point was subsequent revision rates for infection and for any reason in the single and dual ABLC groups. Cumulative crude incidence of revision was calculated using competing risk analysis. Results. A total of 22,308 hip fracture arthroplasties, 2,529 hip revision and 7,124 knee revision arthroplasties were registered and analyzed in the study period. The majority of hip fracture patients (97.1%) was treated with single ABLC. For hip and knee revision arthroplasties dual ABLC was used in 33.8% and 25.7%. The revision rate for infection in the fracture arthroplasty group was not different between groups (0.5% versus 0.8%, p=0.27). The re-revision rate following hip or knee revision based on single versus dual ABLC was not different between groups (3.2% versus 2.8%, p=0.82 for hip revision and 1.8% versus 2.5%, p=0.36 for knee revision). In addition, the re-revision rate for any reason was not different in all three datasets. The crude cumulative revision and re-revision rates for any reason based on single ABLC versus dual ABLC showed no differences in all three datasets. The crude cumulative 7-year re-revision rate for any reason following revision THA with Gentamicin ABLC use was 11.8%, with Gentamicin + Clindamycin ABLC use 13.1% and with Erythromycin + Colistin ABLC use 14.8% (ns). The crude cumulative 9-year re-revision rate for any reason following revision TKA with Gentamicin ABLC use was 17.7% and with Gentamicin + Clindamycin ABLC use 16.5% (ns). Conclusions. In conclusion, we could not show a difference in revision rate for hip fracture arthroplasty or re-revision rates for revision hip- or knee arthroplasty with the use of dual ABLC compared to single ABLC bone cement, with 7and 9 year follow up. The low percentage of dual ABLC in hip fracture arthroplasties in our registry do not enable us to make a reliable estimation of the added value in this patient category. The results of this study do not confirm the potential benefit of dual ABLC use in revision cases

Background. Exebacase, an antistaphylococcal lysin in Phase 3 of development as a treatment for S. aureus bacteremia/right-sided endocarditis has demonstrated antibiofilm activity in vitro and has previously been used as salvage therapy in four patients with relapsing multidrug-resistant (MDR) S. epidermidis knee prosthetic joint infection (PJI) using a procedure called LysinDAIR (administration of the lysin during the performance of an arthroscopic DAIR). Materials/methods. We performed a single center, exploratory, open-label prospective study using the LysinDAIR procedure in patients with chronic (inoculation >3 months prior to treatment) coagulase-negative staphylococci (CNS) PJI of the knee with two different clinical presentations and treatment paradigms. Cohort A: first episode of CNS knee PJI, for whom the LysinDAIR was followed by clindamycin + levofloxacin planned to be prescribed for three months and then stopped; and Cohort B: relapsing episodes of MDR CNS knee PJI for whom the LysinDAIR was followed by primary antimicrobial therapy for three months, followed by suppressive antimicrobial therapy (SAT). Exebacae susceptibility testing was performed before treatment for each patient. In agreement with the French Health authority, exebacase (2 to 3.5 total mg in 30–50 ml (∼0.067 – 0.075 mg/m) was administered directly into the joint during arthroscopy. Results. Eight patients were treated. Exebacase administration was well tolerated by all patients and no serious adverse drug reactions to exebacase were reported. In cohort A (n=4), patients had susceptible S. epidermidis PJI, a painful joint effusion without fistula and without loosening, and received three months of levofloxacin + clindamycin (one patient received an alternative regimen following antibiotic adverse events) and then antibiotics were stopped. During a follow-up of 14, 19, 26 and 36 months, no relapse, no recurrence of the joint effusion and no loosening occurred. In cohort B (n=4), patients had MDR CNS, clinical signs of septic arthritis with a joint effusion without fistula and without loosening and received daptomycin + linezolid or doxycycline. One patient died from COVID-19 at week 4. SAT (tedizolide, n=2; doxycycline, n=1) was then prescribed to other patients. One experienced an infection relapse involving S. caprae under tedizolid therapy at six months. The two other patients continue to do well under SAT 8 and 12 months after the LysinDAIR procedure. Conclusions. The LysinDAIR procedure is a minimally invasive procedure, which has been shown to be easy-to-perform, safe, and has the potential for use as initial treatment or salvage therapy in patients with CNS chronic knee PJI

Introduction. Introduction: Pin site infection is a common complication during treatment with a circular frame external fixator and increases time and support patients require from the limb reconstruction team. Wound swabs were not routinely sent by the clinical nurse specialists prior to this study, with most pin site infections treated as Staphylococcus aureus with flucloxacillin (clindamycin in penicillin allergy). The aim of this study was to ascertain whether routine sending of wound swabs in pin site infection would change antibiotic treatment. Materials & Methods. Materials and Method: Patients presenting at clinic or physiotherapy with clinical signs of pin site infection were assessed using the Maz Oxford Nuffield (MON) Pin Site Infection Grading System© (OUH, 2021). Antibiotics were commenced as per unit guidelines and swabs sent for microscopy, culture and sensitivity. Results. Results: There were forty patients treated with pin site infections. Swab results showed S. aureus in 60% (N=24), other organisms in 15% (N=6) and no growth or mixed skin organisms in 10% (N=10). Flucloxacillin was prescribed to 77.5% (n=31) of patients with the remaining 22.5% (n=9) of patients receiving clindamycin (due to allergy) or rifampicin and ciprofloxacin (due to a previous MRSA diagnosis). Antibiotic management was subsequently changed in only 5% (n=2) of patients due to one patient with a new MRSA diagnosis and one patient growing Enterobacter in three pin sites tested. Conclusions. Conclusion: This study has shown that routine swab testing of pin sites does not usually change antibiotic management but should still be used in multiple, severe or unresolving pin site infections

An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing

Abstract Background. The treatment of bone and joint infections (BJI) involving multi-drug resistant bacteria remains a challenge. MDR Staphylococcus epidermidis (MDRSE) clones, resistant to methicillin, clindamycin, levofloxacin, rifampicin and even linezolid, have been reported worldwide. The interest of delafloxacin (DFX), theoretically active on MRSA, remains to be evaluated with respect to MDRSE. Purpose. Our objective was to evaluate during a retrospective multicenter study the DFX minimal inhibitory concentrations (MICs) and compare its efficacy between ofloxacin-susceptible and ofloxacin-resistant S. epidermidis clinical strains involved in BJI. Methods. In this multicenter retrospective study (Reference centers from the West part of France, CRIOGO), 529 strains were collected mostly from BJI. DFX MICs were determined by using a 0.5 Mc Farland bacterial inoculum on Mueller-Hinton agar plates with gradient strips incubated for 24h at 35°C. For S. aureus, breakpoints differentiate skin and soft tissue infections from other infections. Breakpoints followed 2022 EUCAST criteria, with S. aureus values adopted for S. epidermidis. Results. Of the 529 strains collected, 355 were from prosthetic infections, 159 from synthetic infections and 15 from non-device infections. 152 strains were susceptible to ofloxacin (110 males vs 42 females) and 377 resistant (210 vs 167). As presented in Figure 1, all the ofloxacin-susceptible strains presented a DFX MIC ≤0.006mg/L. Resistant strains presented a double population distribution, with 3.7% categorized susceptible according to skin and soft tissues infections breakpoint, against 88.9% according to other breakpoint infections (0.016 or 0.25mg/L respectively). Conclusion. DFX shows excellent activity against ofloxacine-susceptible strains. Concerning the ofloxacin-resistant strains, more than 80% strains or less than 10% can be considered as DFX-susceptible depending on the breakpoints used. Further clinical studies are needed to validate the real breakpoints that must be used in MDRSE BJI, allowing a microbiological cure and a favourable clinical outcome. For any tables or figures, please contact the authors directly

Aim. Antimicrobial suppression has shown to significantly improve treatment success of streptococcal periprosthetic joint infection (PJI) compared to 12-week standard antimicrobial therapy, however, only short-term follow-up was investigated. In this study we assessed the impact of suppression on the long-term outcome of streptococcal PJI. Method. Consecutive patients with streptococcal PJI (defined by EBJIS criteria) treated 2009–2021 were prospectively included and allocated into standard and suppression (> 6 months) treatment group. Infection-free survival was assessed with Kaplan-Meier-method and compared between the groups with log rank test. Rates of infection-free, streptococcal infection-free and relapse-free status as well as tolerability of suppression were assessed. Results. Sixty-three PJI episodes (36 knee, 26 hip and one shoulder prosthesis) of patients with a median age of 70 (35–87) years were included. Twenty-seven (43%) were females. Predominant pathogens were S. agalactiae (n=20), S. dysgalactiae (n=18) and S. mitis/oralis (n=13). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21). Standard 12-week treatment was administered in 33 patients and suppression in 30 patients, of whom 10 had ongoing suppression and 20 had discontinued antibiotics at time of follow-up. Used oral antibiotics for suppression were amoxicillin (n=29), doxycycline (n=5) and clindamycin (n=2); 6 patients changed antibiotic substance due to side effects. The median follow-up time was 3.9 (0.3–13.3) years. Infection-free survival after 7.5 years was 38% with standard treatment and 62% with suppression (p=0.038). Of all failures, 52% (14/27) were due to streptococci. Suppression was effective in preventing streptococcal infection for the duration of antimicrobial treatment, however, after discontinuation relapses or new infections due to streptococci occurred in 5/20 (25%) patients and infection with any Streptococcus spp. was observed in 9/19 (47%) failures with standard treatment, 5/6 (83%) failures after discontinuing suppression and none during suppression. All failures in patients with ongoing suppression were caused by gram-negative rods. Conclusion. At long-term follow-up, the success rate was superior with suppression compared to standard treatment. Most failures after stopping suppression were caused by streptococci, whereas failures under suppression were caused by aerobic gram-negative rods

Aim. Antimicrobial resistance (AMR) aggravates an already difficult treatment of periprosthetic joint infections (PJI). The prevalence of drug-resistant pathogens varies across countries and increases over time. Regular monitoring of bacteriological analyses should be performed. Due to many factors influencing the AMR, the correct choice of antimicrobial management remains arguable. The primary purpose of this retrospective study was to identify and compare causative bacteria and to compare the incidence of antibiotic resistance between the septic revision total knee arthroplasty (TKA) and septic revision total hip arthroplasty (THA). Method. A review of all revision TKAs and revision THAs, undertaken between 2007 and 2020 in a tertiary referral centre, was performed. Included were cases meeting the consensus criteria for PJI, in which an organism has been identified. There were no major differences in tissue sampling between revision TKAs and revision THAs over time. Results. A total of 228 bacterial strains, isolated after revision TKA and THA, were analysed for their resistance to 20 different antibiotics. There was a statistically significant higher occurrence of Gram-negative bacteria (p=0.002) and Enterococcus species (p=0.026) identified after revision THAs compared to TKA. The comparison of antibiotic resistance between revision TKAs and revision THAs was statistically significant in 9 of 20 analysed antibiotics. Pathogens isolated after revision THA were much more resistant compared to pathogens isolated after revision TKA. Resistance in revision THAs was significantly higher to oxacillin (p=0.03), ciprofloxacin (p<0.001), levofloxacin (p<0.001), moxifloxacin (p=0.005), clindamycin (p<0.001), co-trimoxazole (p<0.001), imipenem (p=0.01), rifampicin (p=0.005) and tetracycline (p=0.009). There was no significantly higher resistance of pathogens isolated after revision TKAs detected. No statistically significant difference in antibiotic resistance of Gram-negative bacteria between revision TKA and revision THA was observed. Conclusions. The occurrence and the resistance of bacteria to antibiotics differs significantly between revision TKAs and revision THAs. This has implications on of the choice of empirical antibiotic in revision surgery as well as prophylactic antibiotic in primary surgery, depending on the joint that is to be replaced

Background. Antibiotic loaded bone cement spacers are used as an adjunct to treatment in 2-stage arthroplasty revisions. If release of the correct choice of antimicrobials is optimised, systemic therapy might be curtailed and emergence of resistance minimised. Aims: To determine the elution period of antimicrobials from bone cement with and without a copolymer, polyvinylpyrrolidone (PVP) and to limit resistance development by the use of two or more antimicrobials. Methods. Triclosan, gentamicin and clindamycin with and without (PVP) in CMW bone cement, was tested against six bacteria using serial plate transfer. Results. While there was little difference between clindamycin and clindamycin with PVP, and between gentamicin and gentamicin with PVP, there was marked enhancement of release of triclosan with PVP. Resistance developed when antimicrobials were used singly but not when used in combination. Conclusion. The addition of water soluble PVP was expected to enhance elution of antimicrobials from bone cement. This occurred with triclosan, a poorly water-soluble agent, but there was no significant difference for gentamicin and clindamycin, which as preferentially water -soluble. Other copolymers are being explored in an attempt to enhance their release. Triclosan used in combination extended the duration of activity against the test bacteria without development of resistance. Combinations of antimicrobials reduce the risk of paradoxical resistance in bone cement

Aim. North America is facing a rising epidemic involving strains of methicillin-resistant Staphylococcus aureus (MRSA) that, instead of being found almost exclusively in hospitals, are community-associated (CA-MRSA). These strains are aggressive, associated with musculoskeletal manifestations including osteomyelitis (OM), and septic arthritis (SA). We aimed to establish novel management algorithms for acute OM and SA in children. We investigated S.aureus susceptibilities to current first-line antimicrobials to determine their local efficacy. Method. The project was conducted at Nemours General Children Hospital in Florida, USA, following approval by the internal review board. A literature review was conducted. An audit of S.aureus antimicrobial sensitivities was completed over three years and compared against national standards. Susceptibilities of clindamycin, trimethoprim/sulfamethoxazole (TMP/SMX) and vancomycin were studied using local resistance ranges. Results. Two algorithms for acute OM and SA management were created adopting a multidisciplinary team approach from admission to discharge whilst differentiating higher risk patients within fast-track pathways. We analysed 532 microbiology results for antibiotic susceptibilities from 2012 to 2014. Overall, 51% of S.aureus infections were MRSA versus 49% methicillin-susceptible S.aureus (MSSA). Surprisingly, clindamycin resistance rates rose compared to 2005 (MRSA 7% in 2005 vs 39% currently, MSSA 20% vs 31% and total S.aureus resistance rate of 8% vs 35%, respectively). MRSA and MSSA isolates were near 100% sensitive to Vancomycin and TMP/SMX. No appropriate national standards existed. Conclusions. Multidisciplinary based algorithms were created for acute OM and SA treatment in children. Possible therapeutic roles for ultrasound guided aspiration and corticosteroids were highlighted in SA. Our audit revealed equal incidence of MSSA to MRSA, supporting national figures on falling MRSA. Interestingly, increased resistance of MSSA and MRSA was found towards recommended first line clindamycin, raising concern over its efficacy

Aim. Rifampin is considered as the antibiotic corner stone in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin has been questioned. We evaluated the outcome of patients treated with and without rifampin, and analysed the influence of timing, dose and co-antibiotic. Method. Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death, or the need for suppressive antimicrobial treatment. Results. A total of 669 patients were analysed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < 0.001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < 0.001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 – 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone (OR 7.73, 95% CI 4.26 – 14.0) and the start of rifampin within 5 days after surgical debridement (OR 1.88, 95% CI 1.05 – 3.35) were predictors of treatment failure. Clindamycin demonstrated similar efficacy as co-antibiotic. The dosing of rifampin had no effect on outcome. Conclusions. Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged

Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD

Introduction. First generation cephalosporins remain the gold standard perioperative antibiotic for total hip and knee arthroplasty (THA, TKA). However, some patients have documented or self-reported allergies to antibiotics, most commonly penicillin, that result in changes to perioperative antibiotic coverage. Furthermore, patients testing positive for methicillin resistant staphylococcus aureus (MRSA) represent another group where an alternative to cefazolin, typically vancomycin, is often chosen for perioperative prophylaxis. The aims of this study were to 1) characterize the antibiotic choices for perioperative prophylaxis at the time of primary TKA and THA, 2) assess the efficacy of a preoperative antibiotic allergy testing program, and 3) determine rates of periprosthetic joint infection (PJI) based on perioperative antibiotic regimen. Methods. We evaluated all patients undergoing primary TKA or THA at a single academic institution from January 2004-May 2017, yielding a cohort of 29,695 patients. A series of institutional databases were combined to determine which patients underwent antibiotic allergy testing prior to surgery, outcomes from the allergy consultation, perioperative antibiotic management strategy, and survivorship free of infection until final follow-up. Results. Antibiotic allergy testing was performed in 3,411 patients (11.5%) on the basis of a patient provided history of possible penicillin or cephalosporin allergy. Among those tested, 3,310 patients (97.0%) were cleared by the allergist to use cephalosporins in the perioperative period and 2,883 patients (87.1%) eventually received cefazolin. For the entire cohort, 28,174 patients (94.9%) received an operative antibiotic regimen including cefazolin and 1,521 patients (5.1%) received non-cefazolin antibiotics, most commonly vancomycin or clindamycin. Survivorship free of PJI was significantly higher among patients receiving cefazolin compared to non-cefazolin antibiotics with the most rapid divergence occurring within 2 months of surgery (p<0.001) (Figure 1). Survivorship free of PJI in the cefazolin compared to the non-cefazolin groups was 99.40% vs 99.34% at 1 month, 99.11% vs 98.55% at 2 months, 98.83% vs 98.22% at 1 year, and 98.15% vs 96.96% at 10 years (Table 1). Notably, the increased PJI rate observed in the non-cefazolin group was not attributable to high preoperative MRSA prevalence as 0 of the 38 PJIs grew MRSA on culture. The number needed to treat with cefazolin to prevent 1 PJI was 164 patients at 1-year and 84 patients at 10-years. Therefore, potentially 6,098 PJIs could be prevented by 1-year and 11,905 by 10-years in a cohort of 1,000,000 primary TKA and THA patients. Conclusions. This study demonstrates a significantly higher rate of PJI when non-cefazolin antibiotics are used for prophylaxis during primary TKA and THA, which is likely attributable to the superior spectrum of coverage for common PJI organisms compared to vancomycin or clindamycin. This is supported by the increased rate of non-MRSA PJI observed in the non-cefazolin cohort. Furthermore, cefazolin has been shown to act synergistically with vancomycin against MRSA. This work highlights the positive impact of a formal preoperative antibiotic allergy testing program to increase cefazolin usage. Also, surgeons may consider using cefazolin as a dual agent in the case of known MRSA colonization, whenever possible for PJI prophylaxis during TKA and THA. For any figures or tables, please contact authors directly

Early prosthetic joint infections (PJI) are managed with debridement, implant retention and antibiotics (DAIR). Our aim was to evaluate risk factors for failure after stopping antibiotic treatment. From 1999 to 2013 early PJIs managed with DAIR were prospectively collected and retrospectively reviewed. The main variables potentially associated with outcome were gathered and the minimum follow-up was 2 years. Primary endpoint was implant removal or the need of reintroducing antibiotic treatment due to failure. A total of 143 patients met the inclusion criteria. The failure rate after a median (IQR) duration of oral antibiotic treatment of 69 (45–95) days was 11.8%. In 92 cases PJI was due to gram-positive (GP) microorganisms, in 21 due to gram-negatives (GN) and 30 had a polymicrobial infection. In GP infections, combination of rifampin with linezolid, cotrimoxazole or clindamycin was associated with a higher failure rate (27.8%, P=0.026) in comparison to patients receiving a combination of rifampin with levofloxacin, ciprofloxacin or amoxicillin (8.3%) or monotherapy with linezolid or cotrimoxazole (0%) (Figure 1). Among patients with a GN infection, the use of fluoroquinolones was associated with a lower failure rate (7.1% vs 37.5%, P=0.044). Duration of antibiotic treatment was not associated with failure. The only factor associated with failure was the oral antibiotic selection, but not the duration of treatment. Linezolid, cotrimoxazole and clindamycin but not levofloxacin serum concentrations are reduced by rifampin; a fact that could explain our findings. Further studies monitoring serum concentration could help to improve the efficacy of these antibiotics when combining with rifampin