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

The 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

Antibiotic-associated Clostridium difficile diarrhoea may complicate surgery for proximal femoral fracture. We undertook a 4 year case control study to evaluate the effects of a change in antibiotic prophylaxis in our department. In the period January 2003 to January 2005, patients received three doses of cefuroxime (1.5 g). The new regimen is a single dose of cefuroxime (1.5 g) with gentamicin (240 mg) at induction. Prior to the change in prophylaxis, 912 patients underwent surgery for neck of femur fracture. Following the change, 899 patients underwent surgery over the period March 2005 to March 2007. 38 patients developed C. difficile infection (4.2%) in the initial group, compared with 14 patients (1.6%) in the group following the change in prophylaxis (P=0.009). Patients with C difficile infection also had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and inpatient mortality. The main challenges regarding antibiotic selection are failure of prophylaxis, often because of infection with MRSA, and C. difficile-associated diarrhoea as a consequence of antibiotic prophylaxis. Infection with C. difficile is reduced with the new regimen. We advocate the use of the new regimen as an effective alternative to multiple dose cephalosporins for the prevention of C. difficile infection in this group of high risk patients

Introduction: Antibiotic-associated Clostridium difficile diarrhoea may complicate surgery for proximal femoral fracture. We sought to determine whether a change in antibiotic policy in our unit influenced rates of infection with C. difficile following hip fracture surgery. Methods: A 4 year case controlled study. A change in antibiotic prophylaxis was introduced during a 3 month period in 2005. Infection rates with C. difficile were compared for 2 years either side of this period. The initial regimen was one of three doses of cefuroxime (1.5 g). The new regimen is a single dose of cefuroxime (1.5 g) with gentamicin (240 mg) at induction. Infection was defined as diarrhoea with a positive isolate within 30 days of surgery. Results: Prior to the change in prophylaxis, 912 patients underwent surgery for neck of femur fracture. Following the change, 899 patients underwent surgery over the period March 2005 to March 2007. 38 patients developed C. difficile infection (4.2%) in the initial group, compared with 14 patients (1.6%) in the group following the change in prophylaxis (P=0.009). Patients with C difficile infection also had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and inpatient mortality. Discussion: The main challenges regarding antibiotic selection are failure of prophylaxis, often because of infection with MRSA, and C. difficile-associated diarrhoea as a consequence of antibiotic prophylaxis. Infection with C. difficile is reduced with the new regimen. We advocate the use of the new regimen as an effective alternative to multiple dose cephalosporins for the prevention of C. difficile infection in this group of high risk patients

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

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

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. Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up. Methods. A retrospective review of 1,060 patients who underwent TKA between May 2016 to July 2020 was performed. There were 572 patients in the IV group and 488 in the IO group, with minimal 30 days of follow-up. Patients were followed up at regularly scheduled intervals (two, six, and 12 weeks). No differences between groups for age, sex, BMI, or baseline comorbidities existed. The IV group received an IV dose of 15 mg/kg vancomycin given over an hour preceding skin incision. The IO group received a 500 mg dose of vancomycin mixed in 150 ml of normal saline, injected into proximal tibia after tourniquet inflation, before skin incision. All patients received an additional dose of first generation cephalosporin. Evaluation included preoperative and postoperative serum creatinine values, tourniquet time, and adverse reactions attributable to vancomycin. Results. Incidence of PJI with minimum 90-day follow-up was 1.4% (eight knees) in the IV group and 0.22% (one knee) in IO group (p = 0.047). This preliminary report demonstrated an reduction in the incidence of infection in TKA using IO vancomycin combined with a first-generation cephalosporin. While the study suffers from limitations of a retrospective, multi-surgeon investigation, early findings are encouraging. Conclusion. IO delivery of vancomycin after tourniquet inflation is a safe and effective alternative to IV administration, eliminating the logistical challenges of timely dosing. Cite this article: Bone Joint J 2021;103-B(6 Supple A):13–17

Aim. Currently, gram-negative bacteria (GNB), including multidrug-resistant (MDR-GNB) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). To characterize the antimicrobial resistance patterns of Gram-negative bacteria (GNB) causing hip prosthetic joint infections in elderly patients treated at a Brazilian tertiary academic hospital. Method. This is a retrospective, cross-sectional study of patients over 60 years of age undergoing hip arthroplasty from 2018 to 2023 at a tertiary academic trauma, which were diagnosed with hip prosthetic joint infection. PJI diagnosed was based on EBJIS criteria, in which intraoperative tissue cultures identified the pathogens. Demographics, reason for arthroplasty, type of implant and susceptibility patterns using disk diffusion method were analysed. Results. Overall, among 17 elderly patients diagnosed with hip infected arthroplasty, 45 bacterial isolated were identified. Debridement, irrigation, antibiotic and implant retention (DAIR) procedures due to uncontrolled infection occurred in 47.0% (n=8/17), and five patients underwent more than two DAIR surgeries. Tissue cultures yielded eleven different bacterial species, with GNB accounted for 64.4% (n=29/45) of pathogens. Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa were identified in 34.5% (n=10/29), 17.25% (n=5/29), 13.8% (n=4/29), and 13.8% (n=4/29), respectively. In the resistance profile analysis, E. coli was most sensitive to antibiotics, whereas K. pneumoniae showed resistance rates higher than 70% for cephalosporins, carbapenems, and quinolones. All A. baumannii isolates were resistant to meropenem, and 80% of these isolates were resistant to amikacin. Conclusions. This study emphasizes the role of GNB in the microbiological profile of PJI among elderly patients at a tertiary hospital in a Brazilian centre. The present study portrays a worryingly higher rates of MDR-GNB, mainly to quinolones and cephalosporins resistance which have been the cornerstone of PJI antibiotic treatment. In addition, higher rates carbapenems and aminoglycosides resistance shows a threat to antibiotic treatment of PJI. More global studies need to be carried out to show a likely change in the microbial epidemiology of PJI

Aim. Suppressive antimicrobial therapy (SAT) is used worldwide for patients with a prosthetic joint infection (PJI but clear definitions or guidelines regarding the indications, antimicrobial strategy or treatment duration are currently lacking in the literature. The aim of this study was to identify the global differences in the clinical practice of SAT for PJI. Method. An online survey was designed to investigate the current opinion on indication and treatment goals, preferred antimicrobial drugs, dosing and treatment duration and follow-up of patients with PJI on suppression. The survey was distributed using e-mail lists of several international bone and joint infection societies and study groups. Recipients were asked to share the survey with colleagues who were not a member of one of the societies but who were involved in PJI care. Results. The questionnaire was fully completed by 330 physicians from 43 different countries on six continents (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 14%). Antimicrobial treatment for PJI was discussed in a multidisciplinary team in Europe (90%), Oceania (42%) and North America (12%). In six of eight (75%) different clinical scenarios, respondents from North America would most often place a patient on SAT. In seven of eight (88%) scenarios, SAT was started least often by European respondents. The presence of a fistula was considered a contra-indication for suppression by 74 respondents (22%). First choices of SAT for staphylococcal PJI were: oral cephalosporins (39%) and tetracyclines (31%) in North America; anti-staphylococcal penicillins (55%) and oral cephalosporins (24%) in Oceania; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe. For streptococcal PJI, most clinicians preferred penicillins (91% in Oceania, 67% in Europe, and 53% in North America). Preferred SAT for gram negative PJI was: fluoroquinolones and a penicillin/betalactamase inhibitor in North America (26% and 18%, respectively) and Oceania (23% and 27%, respectively); fluoroquinolones (31%) and Cotrimoxazole (28%) in Europe. The dosage of SAT was never lowered (n=126, 38%), standardly lowered for all antibiotics (n=79, 24%) or only lowered for specific antibiotics (n=125, 38%). SAT was prescribed for an indefinite duration (n=43, 13%), as fixed duration between six months and three years (n=104, 32%) or for an undetermined prespecified duration (n=154, 47%). Conclusions. Substantial variation in the practice of SAT for PJI exists between physicians worldwide and throughout the different continents. This reflects the paucity of data regarding the indication and treatment of PJI with SAT

Aim. The current recommendation in Norway is to use four doses of a first-generation cephalosporin (cefazolin or cephalotin) as systemic antibiotic prophylaxis (SAP) the day of surgery in primary joint arthroplasty. Due to shortage of supply, scientific development, changed courses of treatment and improved antibiotic stewardship, this recommendation has been disputed. We therefore wanted to assess if one dose of SAP was non-inferior to four doses in preventing periprosthetic joint infection (PJI) in primary joint arthroplasty. Method. We included patients with primary hip- and knee arthroplasties from the Norwegian Arthroplasty Register and the Norwegian Hip Fracture Register for the period 2005-2023. We included the most used SAPs (cephalotin, cefazolin, cefuroxime, cloxacillin and clindamycin), administered as the only SAP in 1-4 doses, starting preoperatively. Risk of revision (Hazard rate ratio; HRR) for PJI was estimated by Cox regression analyses with adjustment for sex, age, ASA class, duration of surgery, reason for- and type of arthroplasty, and year of primary arthroplasty. The outcome was 1-year reoperation or revision for PJI. Non-inferiority margins were calculated for 1, 2 and 3 doses versus reference of 4 doses of SAP at the day of surgery, against a predetermined limit of 15% increased risk of PJI. Results. In total 274,188 primary arthroplasties (total hip 133,985, hemi hip 51,442, and total knee 88,761) were included. Of these primary arthroplasties, 2,996 (1.1%) had subsequent revisions for PJI during the first postoperative year. One dose of SAP was given in 9,603 arthroplasties, two doses in 10,068, three doses in 18,351, and four doses in 236,166 arthroplasties. With the recommended four doses as reference, the HRR (95% CI) for 1-year revision for infection was 0.9 (0.7-1.1) for one dose, 1.0 (0.8-1.2) for two doses, and 0.9 (0.8-1.1) for three doses. The corresponding adjusted 1-year revision incidences for PJI was 0.9 (0.7-1.1), 1.0 (0.8-1.2), 0.9 (0. 8-1.1) and 1.0 (1.0-1.1) for one, two, three and four doses respectively, and less than four doses was found to be non-inferior. Conclusions. One preoperative dose of SAP in primary joint arthroplasty surgery seems to be non-inferior to the current recommendation of four doses of a first-generation cephalosporin as PJI-prophylaxis. This finding may simplify the course of treatment for arthroplasty patients, save costs, and improve antibiotic stewardship

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. 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

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

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

Introduction: Infection remains the single most important complication in elective joint replacement. 1.1% of patients suffer early deep infection and 10–17% of patients superficial infection [. 1. ]. Antibiotic prophylaxis has been used extensively in elective orthopaedic practice, approximately halving the post-operative infection rate [. 2. ]. Cefuroxime is almost universally used in the UK. However there is an increased incidence of multiple drug resistant bacteria within the environment in addition cephalosporin use and resistance is widespread [. 3. ]. Many patients are treated pre-operatively for urinary tract infections with cephalosporins, and a further group of patients are already colonised with cephalosporin resistant staphylococcus. We have previously shown that 8.1% of patients fall into one or other of these categories. Methods: We present a prospective series of 630 serial elective orthopaedic admissions from all orthopaedic disciplines. We have examined notes and reviewed lab records in order to determine outcomes. The centre for disease control [. 4. ] definition was used for suspected infections, and confirmed with wound swabs. 48 cases were confirmed infectious from a suspected 142 cases meeting this definition. Results: We found a positive correlation between previous urine infection, MRSA status, revision surgery, and diabetes and wound infection. Nearly 35% of bacterium cultured were cephalosporin resistant, and 12% demonstrated multiple antibiotic resistance. Discussion: It is good clinical practice to provide antibiotic prophylaxis in joint replacement, but the blind use of cephalosporins in all patients does not make sense because of increased incidence of antibiotic resistant bacteria. We present evidence based guidelines for the use of antibiotic prophylaxis in elective orthopaedic surgery and empirical antibiotic treatment in patients with wound infection before culture results are available

Perioperative antibiotic prophylaxis remains one of the most important strategies for prevention of periprosthetic joint infection (PJI) with current guideline recommending a first or second generation cephalosporin. Penicillin (PCN) allergy is often reported by patients, which often results in avoidance of administration of cephalosporins due to fear of cross-reactivity. Alternative medications, such as vancomyin, are often used despite reduced antimicrobial coverage. The purpose of this study was to determine if PCN allergic patients who received vancomycin alone prior to elective primary total joint arthroplasty were at increased risk of developing a subsequent PJI. A retrospective review of 7,602 primary total joint arthroplasties (TJAs) performed between 2005 and 2013 in two institutions were identified using a prospective institutional database. Patient reported PCN or cephalosporin allergy was electronically queried from the anesthesia note. Patients who recieved multiple prophylactic antibiotics, or had unavailable perioperative antibiotic information, or those who received medication other than cefazolin and vancomycin were excluded. PJI was determined using a cross-match with an institutional PJI database constructed from International Classification of Diseases (ICD)-9 codes. Logistic regression analysis was then performed to evaluate the risk of subsequent PJI. The rate of PJI was 1.4% (32/2296) in patients with a reported PCN allergy that received vancomycin alone versus 1.1% (59/5306) in non-PCN allergic patients that received cefazolin alone. The multivariate analysis, with the given sample size, did not detect a statistically significant increased risk of PJI when vancomycin was administered alone (adjusted odds ratio: 1.23, 95% CI 0.6–3.1, p=0.35). While there was no significant differences in the organism profile between PJIs in both groups, the rate of PJI caused by resistant organisms was higher in patients who received vancomycin alone (11.9%, 7/59) compared to those who received cefazolin (3.1%, 1/32). While administration of perioperative prophylactic vancomycin alone during elective primary arthroplasty does not seem to result in a higher rate of subsequent PJI, patients who received vancomycin alone and developed a PJI were more likely to develop an infection with an antibiotic resistant organism. Future studies are needed to determine the most appropriate prophylactic antibiotic for patients who undergo elective arthroplasty and report PCN allergy

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

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

From 1992 to 1999, 713 total joint arthroplasties were performed in The Department of Orthopaedic Surgery, The University of Hong Kong. Since January 1993, a uniform prophylactic antibiotic regime was employed: one dose of first generation cephalosporin (one gram cephazonlin) on induction and every 4-hourly. In case of sequential bilateral total knee arthroplasty, one gram of cephazolin will be given on induction for the first knee and one hour before the operation on the opposite knee. Antibiotic will be discontinued post-operatively. No significant difference was identified between the infection rate before (1.4%) and after (1.2%) the adoption of the prophylactic antibiotic guidelines (p > 0.4). The study had shown that one dose of first generation cephalosporin is as effective as multiple dose of prophylactic antibiotic, either first or second generation cephalosporin, in preventing infection in total joint arthroplasty