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

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.

Periprosthetic joint infection (PJI) represents a complex challenge in orthopaedic surgery associated with substantial morbidity and healthcare expenditures. The debridement, antibiotics, and implant retention (DAIR) protocol is a viable treatment, offering several advantages over exchange arthroplasty. With the evolution of treatment strategies, considerable efforts have been directed towards enhancing the efficacy of DAIR, including the development of a phased debridement protocol for acute PJI management. This article provides an in-depth analysis of DAIR, presenting the outcomes of single-stage, two-stage, and repeated DAIR procedures. It delves into the challenges faced, including patient heterogeneity, pathogen identification, variability in surgical techniques, and antibiotics selection. Moreover, critical factors that influence the decision-making process between single- and two-stage DAIR protocols are addressed, including team composition, timing of the intervention, antibiotic regimens, and both anatomical and implant-related considerations. By providing a comprehensive overview of DAIR protocols and their clinical implications, this annotation aims to elucidate the advancements, challenges, and potential future directions in the application of DAIR for PJI management. It is intended to equip clinicians with the insights required to effectively navigate the complexities of implementing DAIR strategies, thereby facilitating informed decision-making for optimizing patient outcomes. Cite this article: Bone Joint J 2024;106-B(12):1377–1384

Aim

Successful management of native Joint septic arthritis (SA) hinges on the timely initiation of appropriate antibiotic therapy coupled with thorough joint debridement. Since 2018 we have implemented a protocol for empirical antibiotic in patients with suspected SA recommending amoxicillin/clavulanate (and cotrimoxazole in cases of beta-lactams allergy) based on local flora. Nevertheless we have recently found that institutional compliance to the protocol is only about 50% and many physicians are still choosing alternative wider spectrum regimens.

The aim of this study is to assess whether current clinical and epidemiological characteristics of patients treated for this condition justify an update or whether previous recommendations are still valid.

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

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

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

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

Aim. Whether pre-operative microbiological sampling contributes to the management of chronic peri-prosthetic infection remains controversial. We assessed agreement between the results of pre-operative and intra-operative samples in patients undergoing single-stage prosthesis exchange to treat chronic peri-prosthetic infection. The tested hypothesis was that agreement between pre-operative and intra-operative samples exceeds 75% in patients undergoing single-stage exchange of a hip or knee prosthesis to treat chronic peri-prosthetic infection. Method. This single-centre retrospective study included 85 single-stage prosthesis exchange procedures in 82 patients with chronic peri-prosthetic infection at the hip or knee. Agreement between pre-operative and intra-operative sample results was evaluated. Changes to the initial antibiotic regimen made based on the intra-operative sample results were recorded. Associations between sample agreement and infection-free survival were assessed. Results. Of 149 pre-operative samples, 109 yielded positive cultures, in 75/85 cases. Of 458 intra-operative samples, 354 yielded positive cultures, in 85/85 cases. Agreement was complete in 54 (63%) cases and partial in 9 (11%) cases; there was no agreement in the remaining 22 (26%) cases. The complete agreement rate was significantly lower than 75% (p=0.01). The initial antibiotic regimen was inadequate in a single case. Agreement between pre-operative and intra-operative samples was not significantly associated with infection-free survival. Conclusions. Pre-operative sampling may contribute to the diagnosis of peri-prosthetic infection but is neither necessary nor sufficient to confirm the diagnosis and identify the causative agent. The spectrum of the initial antibiotic regimen cannot be safely narrowed based on the pre-operative sample results. We suggest the routine prescription of a probabilistic broad-spectrum antibiotic regimen immediately after the prosthesis exchange, even when a pathogen was identified before surgery. No funding from any part was received for the purpose of this study

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. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

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

Aims. To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods. Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results. MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion. The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article:Bone Joint Res. 2020;9(2):49–59

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

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. Acute kidney injury is a recognised post-operative complication in primary joint replacement. Recently it has been demonstrated that antibiotic regimen can significantly impact on the proportion of patients who develop acute kidney impairment post-operatively. Within our unit an increased rate of acute kidney injury had been noted post-operatively over the last 5 years. This increase followed the introduction of a rapid recovery protocol for arthroplasty patients. Our aim was determine whether we could identify a causative factor or those who were at increased risk of post-operative renal impairment. Methods. Data were collected for 413 patients initially retrospectively but continued prospectively. Univariable and multivariable analysis was performed to determine any causative factors. The primary increase was 150% increase in baseline creatinine, but as some authors recognise an increase in 125% this was also analysed. Results. Within the 12 month period studied 23.3% of patients developed acute kidney injury, with an increase of 125% of their baseline creatinine. 8.23% of patients developed an increase of 150% in their creatinine levels. Age, previous renal failure and the pre-operative use of an ACE inhibitor were found to be statistically higher in the renal failure group. The uni-variable analysis also demonstrated that patients who received a small volume of post-operative intravenous fluids had a lower rate of renal failure than those who received no fluids (10% vs. 23%; p = 0.04). The multivariable regression analysis demonstrated that age was the only statistically significant positive predictive factor in developing renal failure. Antibiotic regimen had no effect. Discussion. Renal impairment has significant impact on patient morbidity and post-operative management. It increases the length of stay, and may potentially require more invasive therapy. We have demonstrated that the identified risk factors are non-modifiable but that a gentamicin and teicoplanin regimen was not an implicated causative factor

Aim. Antibiotic prophylaxis is central in preventing postoperative spine infections, yet knowledge of clinical spine tissue antibiotic concentrations remains limited. Pooled postoperative spine infection rates are constant (approximately 3%), resulting in severe patient morbidity, mortality, and prolonged hospitalization. Current antibiotic dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures (plasma samples), non-clinical evidence (experimental models), and inferior methodology (tissue specimens). Therefore, personalized antibiotic dosing may be the future of antibiotic prophylaxis to prevent postoperative infections, especially implant infections. The aim was to continuously evaluate intra- and postoperative cefuroxime target spine tissue concentrations in long-lasting spine surgery after personalized dosing by repeated weight-dosed intravenous administrations. Method. Twenty patients (15 female, 5 male) scheduled for long-lasting spine deformity surgery with hypotensive anaesthesia were included; median age (range): 17.5 years (12-74), mean BMI (range): 22.2 (16.2-37.7), and mean surgery time (range): 4h 49min (3h 57min-6h 9min). Weight-dosed cefuroxime (20 mg/kg) was administered intravenously to all patients on average 25 min before incision and repeated after 4 hours. Microdialysis catheters were placed for sampling of cefuroxime concentrations in vertebral bone (only intraoperative sampling), paravertebral muscle, and subcutaneous tissue as soon as possible after surgery start. Upon wound closure, two additional catheters were placed in the profound and superficial part of the wound. Microdialysis and plasma samples were obtained continuously intra- and postoperative for up to 12 hours. The primary endpoint was (based on cefuroxime time-dependent efficacy) the time with cefuroxime concentrations above the clinical breakpoint minimal inhibitory concentration for Staphylococcus aureus of 4 µg/mL in percentage (%fT>MIC4) of. (a). patients’ individual surgery time,. (b). first dosing interval (0-4 hours),. (c). second dosing interval (4-12 hours). Results. Mean cefuroxime %fT>MIC4 (range) of:. (a). patients’ individual surgery time was 100% (100-100%) in all investigated tissues. (b). the first dosing interval was 93% (93-93%) in vertebral bone, paravertebral muscle, subcutaneous tissue, and 99% (99-100%) in plasma. (c). the second dosing interval was 87% (52-100%) in paravertebral muscle, 89% (52-100%) in subcutaneous tissue, 91% (71-100%) in the profound wound, 94% (72-100%) in the superficial wound, and 71% (42-100%) in plasma. Conclusions. Personalized cefuroxime dosing by repeated weight-dosed (20 mg/kg) intravenous administrations provided homogenous and therapeutic spine tissue exposure across all investigated tissues and plasma in long-lasting spine surgery with hypotensive anaesthesia (up to 11 hours). Thus, personalized cefuroxime dosing may decrease the risk of postoperative spine infection, especially in cases with implant insertion

Purpose of the study: Staphylococcus lugdunensis, described in Lyon in 1988 by Freney, appears to be a member of the cutaneous perineal flora. Since the first description, S. lugdunensis infections are regularly reported. The germ has been reported as the causal agent for endocarditis on valve prostheses with a very severe prognosis, requiring surgery in addition to medical management. We wanted to ascertain the prognosis of such infections on joint prostheses and to determine if it is different from that with other staphylococcal species. Material and methods: Since 1991, seven S. lugdunensis infections on a joint prosthesis (three total hip prostheses and four total knee arthroplasties) were identified in our department. The Api Id 32 staph (BioMérieux SA) test battery was used for identification. All patients underwent surgical treatment and were given a prolonged antibiotic regimen. Simple joint cleaning was performed in three cases, one requiring a one-stage prosthesis replacement. There were four two-stage prosthesis replacements. The antibiotic regimen was always long (3–8 months) and was continued as a palliative treatment in two patients who underwent simple cleaning. Results: One elderly woman with multiple co-morbid conditions died after prosthesis removal before the replacement procedure could be performed. There were no cases of recurrent infection at 16 months and 6 years for the four prosthesis replacements (one- and two-stage procedures). Arthroscopic cleaning without removal of the TKA was a failure in one patient who required prosthetic replacement later. Two simple cleanings in elderly patients were failures and required continuous palliative antibiotics. Discussion:Staphylococcus lugdunensis is generally considered to be very susceptible to antibiotics in vitro. In our experience, search for minimum inhibitory concentrations and minimum bactericidal concentrations have shown cures with rapid shifts which must be taken into consideration when choosing an antibiotic. With surgical removal of the prosthesis and adapted antibiotics, the prognosis of these infections is not different from other staphylococcal infections of joint prostheses. We did however note two cases of secondary infections, probably related to hematogeneous spread, which developed from an unidentifiable point in time. Conclusion:Staphylococcus lugdunensis is a coagulase-negative staphylococcus with poorly known virulence properties. In our very small series of joint prostheses infections, therapeutic failure occurred when the infected prosthesis was not removed

Aim. Propionibacterium acnes (PA) is an important cause of shoulder prosthetic joint infections (SPJIs) for which the optimal treatment has not yet been determined. Rifampicin and Levofloxacin both showed not benefit in recent experimental models of PA-SPJIs. We describe herein the experience of five different medical French centers in order to assess factors associated with patient's outcome with special emphasize on antibiotic regimens. Method. A multicentric retrospective study was performed, on consecutive patients with PA – related SPJIs diagnosed on the basis of at least 2 or more positive cultures of either per-operative or joint aspiration and clinical history compatible with a PJI according to the current guidelines. All patients had surgical management, followed by systemic antibiotic therapy. Remission was defined as an asymptomatic patient with functioning prosthesis at the last contact. Results. Fifty-nine patients of mean age 66.2 ± 10.5 years were included. Most patients were at least ASA 2 (66%), 8 (14%) diabetes mellitus, 3 (5%) had neoplasia. Fourteen patients (24%) had acute, 34 (58%) subacute, and 11 late infections (19%). The mean delay from symptoms of infection to surgery was 89 ± 141 days (1–660). Surgical management consisted in implant exchange in 40 (68%) patients. Antibiotic treatment included mainly clindamycin (49%), levofloxacin (44%) and rifampin (17%), with a mean duration of 52.3 ± 31.9 days. The mean follow-up duration was 540 days ± 488 (range 12 ™ 1925). Forty-five patients were in remission (76%) in this study, 8 patients had a relapsing infection (14%), 1 a recurrence (2%) and 5 a superinfection ™ i.e, due to a different pathogen − (8%). In monovariate analysis, rifampicin/levofloxacin treatment was significantly associated with failure (p=0.038). In multivariate analysis, levofloxacin use and implants retention were significantly related to failure (p=0.02 and p=0.003, respectively). Conclusions. Our results suggest that implant retention and levofloxacin use are two independents factors of failure in patients treated for PA – related SPJIs

Aim. Open fractures still have a high risk for fracture-related Infection (FRI). The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial due to heterogeneous guidelines and highly variable prophylactic regimens in clinical practice. In order to provide further evidence with which to support the selection of antibiotic duration for open fracture care, we performed a preclinical evaluation in a contaminated rabbit fracture model. Method. A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole-LCP and inoculated with Staphylococcus aureus (2×106 colony forming units, CFU per inoculum). This inoculum was previously shown to result in a 100% infection rate in the absence of any antibiotic prophylaxis. Cefuroxime was administered intravenously in a weight adjusted dosage equivalent to human medicine (18.75 mg/kg) as a single shot only, for 24 hours (every 8 hours) and for 72 hours (every 8 hours) in separate groups of rabbits (n=6 per group). Infection rate per group was assessed after two weeks by quantitative bacteriological evaluation of soft tissue, bone and implants. Blood samples were taken from rabbits preoperatively and on days 3, 7 and 14 after surgery to measure white blood cell count (WBC) and C-reactive protein (CRP) levels. Results. Duration of PAP had a significant impact on the success of antibiotic prophylaxis. The single shot regimen completely failed to prevent infection. All samples (soft tissue, implant and bone) from this group displayed high numbers of bacteria. Additionally, abscesses were present in two of six rabbits. The 24-hour regimen showed a reduced infection rate (1 out of 6 rabbits infected), but only the 72-hour course was able to prevent FRI in all animals in our model. After an initial postoperative peak on day three, CRP levels then decreased to baseline (approx. 30 µg/ml) in the 24h-group and 72h-group, but remained significantly higher in the single shot group at day 7 and 14 (p<0.05). Conclusions. When contamination with high bacterial loads is likely (e.g. in an open fracture situation), a 72-hour course of intravenous cefuroxime appears to be superior in preventing FRI compared to a single shot or 24-hour antibiotic regimen. Acknowledgements. This work was funded by AOTrauma