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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.

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

BackgroundThe avascular capsule around the generator of the cardiac implantable electronic device (CIED) could be susceptible to bacterial colonization and source of infection. Capsulectomy during CIED generator replacement may be beneficial in preventing device infection, but there is a lack of evidence.MethodsThis prospective randomized trial, conducted from December 2013 to December 2019, included 195 patients divided equally into two groups. In the intervention group (n = 97), capsule removal was performed on the floor of the pocket, while it was not performed in the control group (n = 98). In both groups, swab culture was performed in the pocket. The primary outcome was the occurrence of device infection requiring pocket revision.ResultsA total of 195 patients were included (mean age 70.2 ± 13.6 years, 55.4% women), with an average follow-up period of 54.3 ± 28.9 months. Among 182 patients undergoing microbiological cultures of pockets, 19 (10.4%) were confirmed positive, and Staphylococcus species were identified most frequently. The primary outcome occurred in 4 (2.1%), and there was no significant difference between the two groups (3.1% vs. 1.0%, p = 0.606). Hematoma has occurred in 10 patients (3.1% vs. 7.1%, p = 0.338), one of them required wound revision. In multivariable analysis, the occurrence of hematoma was the only independent risk factor associated with device infection (HR 13.6, 95% CI 1.02–181.15, p = 0.048).ConclusionsIn this long-term prospective study, capsulectomy during the replacement of the generator did not reduce the incidence of device infection. There was no association between bacterial colonization in the capsule around the generator and CIED infection.

BackgroundProximal femur replacements in patients with sarcoma are associated with high rates of infection. This study is the largest one comparing infection rates with titanium versus silver-coated megaprostheses in sarcoma patients.MethodsInfection rates were assessed in 99 patients with proximal femur sarcoma who underwent placement of a titanium (n = 35) or silver-coated (n = 64) megaprosthesis. Treatments administered for infection were also analyzed.ResultsInfections occurred in 14.3% of patients in the titanium group, in comparison with 9.4% of those in the silver group, when the development of infection was the primary end point. The 5- and 10-year event-free survival rates for the prosthesis relative to the parameter of infection were 90% in the silver group and 83% in the titanium group. The overall infection rates were 10.9% in the silver group and 20% in the titanium group. Two patients each in the silver and titanium groups ultimately had to undergo amputation. The need for two-stage prosthesis exchanges (57.1% in the titanium group) declined to 14.3% in the silver group.ConclusionUsing a silver-coated proximal femoral replacement nearly halved the overall infection rate. When infections occurred, it was usually possible to avoid two-stage prosthesis exchanges in the silver group.

Introduction Debridement, Antibiotics and Implant Retention (DAIR) has been the mainstay of treatment for early onset periprosthetic joint infection in spite of variable results. Modular component exchange is a widely recommended strategy to improve success rates with DAIR though very strong evidence to support its practice is still lacking. Materials and methods Eighty six patients underwent DAIR for early onset PJI following primary hip and knee arthroplasty were divided into two groups for this retrospective review. 45 patients (group 1) underwent DAIR with modular component exchange and 41 patients without exchange (group 2). We compared success rates based on infection eradication (primary outcome variable) and need for revision surgical procedures between these two groups. We also assessed differences in primary outcome based on type of arthroplasty, timing of DAIR and addition of local antibiotics. Results The overall success rate after DAIR was 71%. The outcome was similar in both groups (69% vs 74%, P = 0.66). The need for revision surgical procedures was 27% which was similar in both groups (P = 0.98) with 23% needing revision of prosthetic components. Type of arthroplasty (hip or knee) and addition of local antibiotics had no bearing on infection eradication after DAIR with or without modular component exchange. DAIR with in 45 days of primary arthroplasty had significantly higher success rate compared to DAIR after 45 days in both groups. Conclusions We observed that modular component exchange did not improve infection eradication after DAIR for early onset PJI following hip and knee arthroplasty. Reasonable success rates can be expected after DAIR especially if the patient develops early clinical signs and the procedure is carried out as early as possible.

The use of cardiac implantable electronic devices (CIED) has risen steadily, yet the rate of cardiac device infections (CDI) has disproportionately increased. Amongst all cardiac device infections, the pocket infection is the most challenging diagnosis. Therefore, we aimed to improve diagnosis of such pocket infection by identifying relevant biomarkers. We enrolled 25 consecutive patients with invasively and microbiologically confirmed pocket infection. None of the patients had any confounding conditions. Pre-operative levels of 14 biomarkers were compared in infected and control (n = 50) patients. Our selected biomarkers included white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide binding protein, high-sensitivity C-reactive protein (HS-CRP), polymorphonuclear-elastase, presepsin, various interleukins, tumor necrosis factor α (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF). Of the 25 patients with isolated pocket infection (70±13years, 76% male, 40% ICDs), none presented with leukocytosis. In contrast, they had higher serum levels of HS-CRP (p = 0.019) and PCT (p = 0.010) than control patients. Median PCT-level was 0.06 ng/mL (IQR 0.03-0.07 ng/mL) in the study group versus 0.03 ng/mL (IQR 0.02-0.04 ng/mL) in controls. An optimized PCT cut-off value of 0.05 ng/mL suggests pocket infection with a sensitivity of 60% and specificity of 82%. In addition TNF-α- and GM-CSF-levels were lower in the study group. Other biomarkers did not differ between groups. Diagnosis of isolated pocket infections requires clinical awareness, physical examination, evaluation of blood cultures and echocardiography assessment. Nevertheless, measurement of PCT- and HS-CRP-levels can aid diagnosis. However, no conclusion can be drawn from normal WBC-values. clinicaltrials.gov identifier: NCT01619267.

A battery of diagnostic tests is often required to differentiate aseptic loosening from periprosthetic infection since the gold standard remains elusive. We designed a prospective study to determine the accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in diagnosing periprosthetic infection in a large multicenter setting. One hundred and thirteen patients with 127 painful hip prostheses were evaluated by FDG-PET. Images were considered positive for infection if PET demonstrated increased FDG activity at the bone-prosthesis interface of the femoral component. A combination of preoperative tests, intraoperative findings, histopathology, and clinical followup constituted the gold standard for diagnosing infection. Among the 35 positive PET scans, 28 hips were confirmed infected according to our criteria for diagnosing periprosthetic infection. Of the 92 hip prostheses with negative FDG-PET findings, 87 were considered aseptic. The sensitivity, specificity, positive and negative predictive values for FDG-PET were 0.85 (28 of 33), 0.93 (87 of 94), 0.80 (28 of 35), and 0.95 (87 of 92), respectively. The overall accuracy of this novel noninvasive imaging modality reached 0.91 (115 of 127). Based on our results, FDG-PET appears a promising and accurate diagnostic tool for distinguishing septic from aseptic painful hip prostheses. Level of Evidence: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

The removal of all central venous catheters (CVCs) from all patients with candidemia is considered to be standard care. However, this practice is not always possible, and it is associated with significant cost and potential complications. To evaluate the effect of CVC removal on the outcome of patients with candidemia, a literature review was conducted that selected studies that evaluated CVC removal as a prognostic factor (of mortality) in candidemia, performed a multivariate analysis with odds ratios and 95% confidence intervals, and included a validated severity of illness score. Of 203 studies of candidemia, only 4 fulfilled these criteria. One study showed a benefit from CVC removal in a subset of 21 neutropenic patients; another study showed no benefit; and the remaining 2 studies showed a marginal benefit from this strategy. Although it is possible that removal of CVCs may reduce the rate of complications due to candidemia, including death, the findings of this literature review do not substantiate this consensus recommendation.

Background Although large series from national joint registries may accurately reflect indications for revision TKAs, they may lack the granularity to detect the true incidence and relative importance of such indications, especially periprosthetic joint infections (PJI). Questions/purposes Using a combination of individual chart review supplemented with New Zealand Joint Registry data, we asked: (1) What is the cumulative incidence of revision TKA? (2) What are the common indications for revising a contemporary primary TKA? (3) Do revision TKA indications differ at various followup times after primary TKA? Methods We identified 11,134 primary TKAs performed between 2000 and 2015 in three tertiary referral hospitals. The New Zealand Joint Registry and individual patient chart review were used to identify 357 patients undergoing subsequent revision surgery or any reoperation for PJI. All clinical records, radiographs, and laboratory results were reviewed to identify the primary revision reason. The cumulative incidence of each revision reason was calculated using a competing risk estimator. Results The cumulative incidence for revision TKA at 15 years followup was 6.1% (95% CI, 5.1%–7.1%). The two most-common revision reasons at 15 years followup were PJI followed by aseptic loosening. The risk of revision or reoperation for PJI was 2.0% (95% CI, 1.7%–2.3%) and aseptic loosening was 1.2% (95% CI, 0.7%–1.6%). Approximately half of the revision TKAs secondary to PJI occurred within 2 years of the index TKA (95% CI, 0.8%–1.2%), whereas half of the revision TKAs secondary to aseptic loosening occurred 8 years after the index TKA (95% CI, 0.4%–0.7%). Conclusions In this large cohort of patients with comprehensive followup of revision procedures, PJI was the dominant reason for failure during the first 15 years after primary TKA. Aseptic loosening became more important with longer followup. Efforts to improve outcome after primary TKA should focus on these areas, particularly prevention of PJI. Level of Evidence Level III, therapeutic study.