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The appropriate duration of antimicrobial therapy for bacterial prosthetic joint infection is debated. In this open-label, randomized, controlled, noninferiority trial involving 410 patients with prosthetic joint infection at 28 centers across France, antimicrobial therapy for 6 weeks was compared with therapy for 12 weeks and was not found to be noninferior.

Background Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. Questions/purposes (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? Methods Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. Results Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297–19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). Conclusions This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. Level of Evidence Level I, therapeutic study.

Locally applied vancomycin is increasingly being used in primary hip and knee arthroplasty to reduce the risk of infection. Despite encouraging initial results, considerable debate remains on the basis of the data currently available. In particular, it has been unclear up to now whether local vancomycin is suitable to further reduce the risk of infection even if the rate of infection is already low (< 1%). In this monocentric retrospective cohort study, all primary total hip and knee arthroplasties performed between 2013 and 2018 were included. After a change in procedure at the hospital, 1 g vancomycin powder was applied intraarticularly before wound closure. The remaining perioperative procedure was constant over the investigation period. The follow-up was one year. The presence of an infection according to the currently valid MSIS criteria was defined as the endpoint. In patients with TKA two infections (0.3%) were observed under vancomycin prophylaxis in contrast to 44 infections (1.3%) in the control group ( p  = 0.033). In patients with THA two infections (0.5%) were observed under vancomycin prophylaxis and 48 infections (1.1%) in the control group without local vancomycin but this difference was statistically not significant. No wound complications requiring revision were observed as a result of the vancomycin. On the basis of the results of this study, intraarticular application of vancomycin powder in total hip and knee arthroplasty may be considered. Prospective randomized studies have to confirm this promising results prior a common recommendation. Level of Evidence III Retrospective cohort study.

Background The evidence supporting rifampin combination therapy in prosthetic joint infections (PJI) is limited due to the lack of controlled studies. The aim of this study is to evaluate the effect of adding rifampin to conventional antimicrobial therapy in early staphylococcal PJIs treated with debridement and retention of the implant (DAIR). Methods In this multicenter randomized controlled trial, 99 patients with PJI after hip and knee arthroplasties were enrolled. They were randomly assigned to receive rifampin or not in addition to standard antimicrobial treatment with cloxacillin or vancomycin in case of methicillin resistance. The primary endpoint was no signs of infection after 2 years of follow-up. Results Forty-eight patients were included in the final analyses. There were no differences in patient characteristics or comorbidities between the two groups. There was no significant difference in remission rate between the rifampin combination group (17 of 23 (74%)) and the monotherapy group (18 of 25 (72%), relative risk 1.03, 95% confidence interval 0.73 to 1.45, p = 0.88). Conclusion This trial has not proven a statistically significant advantage by adding rifampin to standard antibiotic treatment in acute staphylococcal PJIs. Trial registration The Regional Ethics Committee and the Norwegian Medicines Agency approved the study (EudraCT 2005-005494-29), and the study was registered at ClinicalTrials.gov at Jan 18, 2007 ( NCT00423982 ).

Background Orthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4–6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance. Methods SOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis. Discussion This study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship. Trial registration Clinicaltrials.gov, NCT03806166 . Registered on 11 November 2019.

Procedure-related cardiac electronic implantable device (CIED) infections have high morbidity and mortality, highlighting the urgent need for infection prevention efforts to include electrophysiology procedures. We developed and validated a semi-automated algorithm based on structured electronic health records data to reliably identify CIED infections. A sample of CIED procedures entered into the Veterans’ Health Administration Clinical Assessment Reporting and Tracking program from FY 2008–2015 was reviewed for the presence of CIED infection. This sample was then randomly divided into training (2/3) validation sets (1/3). The training set was used to develop a detection algorithm containing structured variables mapped from the clinical pathways of CIED infection. Performance of this algorithm was evaluated using the validation set. 2,107 unique CIED procedures from a cohort of 5,753 underwent manual review; 97 CIED infections (4.6%) were identified. Variables strongly associated with true infections included presence of a microbiology order, billing codes for surgical site infections and post-procedural antibiotic prescriptions. The combined algorithm to detect infection demonstrated high c-statistic (0.95; 95% confidence interval: 0.92–0.98), sensitivity (87.9%) and specificity (90.3%) in the validation data. Structured variables derived from clinical pathways can guide development of a semi-automated detection tool to surveil for CIED infection.

PurposeTo evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture.MethodsOpen-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. Primary outcome: early-PJI after HHA.ResultsFive hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33–3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15–7.10]).ConclusionsNeither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47

Background In patients with asymptomatic bacteriuria undergoing hip arthroplasty, the risk of prosthetic joint infection (PJI) and appropriateness of specific antibiotics are unclear. Questions/purposes We determined (1) the prevalence of asymptomatic bacteriuria; and (2) the incidence of PJI in patients with asymptomatic bacteriuria managed with or without specific antibiotics. Methods We conducted a prospective, randomized study of all 471 patients without urinary symptoms receiving a total hip arthroplasty (THA; n = 228; average age 68 years; 122 female) or hemiarthroplasty (HA; n = 243; average age 85 years; 170 female) between April 2009 and November 2010. No patients were catheterized in the perioperative period and all received intravenous cefazolin (allergy, vancomycin) for 48 hours postoperatively. Urinalysis was conducted on all patients; if abnormal, a urine culture was performed. Patients with bacteriuria (> 100,000 colonies/mL cultured) were randomly assigned to receive specific antibiotics (Group A) or not (Group B). Minimum followup was 1 month including those six who died or were lost to followup (average, 10.4 months; range, 1–12 months). Results Asymptomatic bacteriuria occurred in eight of 228 patients undergoing THAs (three of eight with specific antibiotics) and 38 of 243 patients undergoing HAs (23 of 38 with specific antibiotics). Arthroplasty infection after 3 months occurred in one of 228 patients undergoing THAs and 12 of 243 patients undergoing HAs (six of 117 in Group A and six of 126 in Group B); bacteria cultured from the wound were dissimilar to those cultured in urine samples in any case. No patient presented signs of PJI by 1 year after the index surgery. Conclusions We identified no case of PJI from urinary origin in patients with asymptomatic bacteriuria whether or not they had been treated with specific antibiotics. Level of Evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

IntroductionChronic hip prosthetic joint infection (PJI) treatment needs non-conservative surgery. The recommended treatment follows a two-stage protocol. Between the two surgeries, full-weight bearing is prohibited, and joint stiffness and pain are rather usual complications. The single-stage procedure is thought to be less susceptible to late functional complications with a shorter, single hospital stay. However, infection control could be less efficient; the protocol highly relies on antibiotics and has a list of contra-indications. Most of these contra-indications are directly related to the biofilm formation. As no randomised control trial has ever compared single-stage versus two-stage surgery on infection treatment, the level of evidence for recommending one procedure over the other is low. An antibiotic-loaded hydrogel coating (Defensive Antiadhesive Coating (DAC), Novagenit SRL) has been proven to mechanically prevent biofilm formation while allowing a prolonged intra-articular antibiotic release. The addition of this biofilm inhibitor to a single-stage surgery might stand as a promising strategy for PJI. Moreover, using this device to prevent biofilm formation could expand one-stage surgery to patients who are in theory contra-indicated to one-stage surgery.Methods and analysisSINBIOSE-H is a Prospective Randomized Open, Blinded End-point clinical trial that will include patients with a chronic hip PJI as defined by the Musculoskeletal Infection Society (MSIS), with at least one theoretical contra-indication for single-stage surgery. Patients needing a cemented implant will not be included. 440 patients will be randomised in two groups: the experimental group is composed of single-stage procedure associated with the use of biofilm inhibitor (DAC) loaded with topical antibiotics, and the control group is composed of two-stage procedure without biofilm inhibitor. The primary objective will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is non-inferior to two-stage surgery for chronic hip PJI treatment. The secondary objectives will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is superior to two-stage surgery on the prevention of functional complications, patient satisfaction scores, death rate, postoperative complications or early revision surgery for any cause other than infection. Based on a failure rate of two-stage surgery of 20% and a reduction of the infection rate using the DAC biofilm inhibitor from 3 to 0.7%, with a non-inferiority margin of 1.35 and power set at 90%, we estimated to enrol 420 patients.Ethics and disseminationThe protocol is in accordance with ethical principles established by the Helsinki World Medical Assembly and its amendments and will be conducted in accordance with the recommendations of International Conference on Harmonisation Good Clinical Practice. A core information and informed consent form will be provided. The written approval of the Ethics Committee (EC)/Institutional Review Board (IRB) together with the approved subject information/informed consent forms must be filed in the study files. Written informed consent must be obtained before any study-specific procedure takes place. The data will be saved on the internal network in a secured directory, dedicated to the study. At the end of the research, all documents (case report files, investigator files, etc) will be archived and stored for 15 years in each centre. Data on SAEs will be included in the study documentation file. All data and documents will be made available if requested by relevant authorities. The EC and IRB were submitted and approved in France (CPP Ile De France X, 93 602 AULNAY-SOUS-BOIS). Ethics approval covers all centres.Trial registration numberThe study is registered on clinicaltrials.org under NCT04251377 (EUDRACT NUMBER, 2019-A01491-56; trial sponsor, St Etienne University Hospital Center; date of the last version, 24 February 2006).

IntroductionThe current evidence on the efficacy of antibiotic-loaded bone cement (ALBC) in reducing the risk of periprosthetic joint infections (PJI) after primary joint reconstruction is insufficient. In several European countries, the use of ALBC is routine practice unlike in the USA where ALBC use is not approved in low-risk patients. Therefore, we designed a double-blinded pragmatic multicentre register-based randomised controlled non-inferiority trial to investigate the effects of ALBC compared with plain bone cement in primary total knee arthroplasty (TKA).Methods and analysisA minimum of 9,172 patients undergoing full-cemented primary TKA will be recruited and equally randomised into the ALBC group and the plain bone cement group. This trial will be conducted in Norwegian hospitals that routinely perform cemented primary TKA. The primary outcome will be risk of revision surgery due to PJI at 1-year of follow-up. Secondary outcomes will be: risk of revision due to any reason including aseptic loosening at 1, 6, 10 and 20 years of follow-up; patient-related outcome measures like function, pain, satisfaction and health-related quality of life at 1, 6 and 10 years of follow-up; risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions at 1, 6, 10 and 20 years of follow-up; cost-effectiveness of routine ALBC versus plain bone cement use in primary TKA. We will use 1:1 randomisation with random permuted blocks and stratify by participating hospitals to randomise patients to receive ALBC or plain bone cement. Inclusion, randomisation and follow-up will be through the Norwegian Arthroplasty Register.Ethics and disseminationThe trial was approved by the Western Norway Regional Committees on Medical and Health Research Ethics (reference number: 2019/751/REK vest) on 21 June 2019. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT04135170.