Do Culture-Negative Periprosthetic Joint Infections Have a Worse Outcome Than Culture-Positive Periprosthetic Joint Infections? A Systematic Review and Meta-Analysis

Background. Culture-negative periprosthetic joint infections (CN PJI) have not been well studied, and due to the lack of consensus on PJI, especially with culture-negative infections, there are considerable uncertainties. Due to the challenging clinical issue of CN PJI the aim of this systematic review is to describe incidence, diagnosis, and treatment outcomes based on the current literature on CN PJI. Hypothesis. The review is designed to assess the formal hypothesis that CN PJI of the hip and knee have a poorer outcome when compared with culture-positive ones. Study Design. It is systematic review with level of evidence 3. Methods. EMBASE, MEDLINE, and the Cochrane Library were searched electronically in January 2018. All studies regarding CN PJI of the hip or knee published in English or German with a minimum of 10 patients were included. Afterwards, the authors performed a descriptive analysis of diagnosis and treatment outcome. Result. Eight studies were identified that met the inclusion criteria. The incidence of CN PJI in the hip or knee ranged from 7% to 42 %. The included studies were pooled to give an overall incidence rate estimate of 11 % [95% confidence interval (CI): 10-12] based on a random-effects model. The most common surgical intervention was the two-stage revision of prosthesis with 283 patients. Postoperatively, the majority of patients received vancomycin as the antibiotic treatment, alone or in combination with other antibiotics. The rate of succesfully treated infections varied from 85% to 95 % in all included studies. The two-stage exchange arthroplasty had the best outcome, based on the infection-free survival rate of 95%, five years after treatment. Conclusions. We conclude that CN PJI have the same or even better results than culture-positive infections. Nonetheless, a standardized diagnostic protocol and evidence-based treatment strategies for CN PJI should be implemented for further studies

Enterococcal periprosthetic joint infection: clinical and microbiological findings from an 8-year retrospective cohort study

BACKGROUND: Treatment of enterococcal periprosthetic joint infections (PJI) is challenging due to non-standardized management strategies and lack of biofilm-active antibiotics. The optimal surgical and antimicrobial therapy are unknown. Therefore, we evaluated characteristics and outcome of enterococcal PJI. METHODS: Consecutive patients with enterococcal PJI from two specialized orthopedic institutions were retrospectively analyzed. Both institutions are following the same diagnostic and treatment concepts. The probability of relapse-free survival was estimated using Kaplan-Meier survival curves and compared by log-rank test. Treatment success was defined by absence of relapse or persistence of PJI due to enterococci or death related to enterococcal PJI. Clinical success was defined by the infection-free status, no subsequent surgical intervention for persistent or perioperative infection after re-implantation and no PJI-related death within 3 months. RESULTS: Included were 75 enterococcal PJI episodes, involving 41 hip, 30 knee, 2 elbow and 2 shoulder prostheses. PJI occurred postoperatively in 61 episodes (81%), hematogenously in 13 (17%) and by contiguous spread in one. E. faecalis grew in 64 episodes, E. faecium in 10 and E. casseliflavus in one episode(s). Additional microorganism(s) were isolated in 38 patients (51%). Enterococci were susceptible to vancomycin in 73 of 75 isolates (97%), to daptomycin in all 75 isolates, and to fosfomycin in 21 of 22 isolates (96%). The outcome data was available for 66 patients (88%). The treatment success after 3 years was 83.7% (95% confidence interval [CI]; 76.1-96.7%) and the clinical success was 67.5% (95% CI; 57.3-80.8%). In 11 patients (17%), a new PJI episode caused by a different pathogen occurred. All failures occurred within 3 years after surgery. CONCLUSION: About half of enterococcal PJI were polymicrobial infections. The treatment success was high (84%). All treatment failures occurred within the first 3 years after revision surgery. Interestingly, 17% of patients experienced a new PJI caused by another pathogen at a later stage

Complications of Resection Arthroplasty in Two-Stage Revision for the Treatment of Periprosthetic Hip Joint Infection

Little data is available regarding complications associated with resection arthroplasty in the treatment of hip periprosthetic joint infection (PJI). We assessed complications during and after two-stage revision using resection arthroplasty. In this retrospective study, 93 patients undergoing resection arthroplasty for hip PJI were included. Patients were assigned to a prosthesis-free interval of ≤10 weeks (group 1; 49 patients) or >10 weeks (group 2; 44 patients). The complication rates between groups were compared using the chi-squared test. The revision-free and infection-free survival was estimated using a Kaplan-Meier survival analysis. Seventy-one patients (76%) experienced at least one local complication (overall 146 complications). Common complications were blood loss during reimplantation (n = 25) or during explantation (n = 23), persistent infection (n = 16), leg length discrepancy (n = 13) and reinfection (n = 9). Patients in group 1 experienced less complications after reimplantation (p = 0.012). With increasing severity of acetabular bone defects, higher incidence of complications (p = 0.008), periprosthetic bone fractures (p = 0.05) and blood loss (p = 0.039) was observed. The infection-free survival rate at 24 months was 93.9% in group 1 and 85.9% in group 2. The indication for resection arthroplasty needs to be evaluated carefully, considering the high rate of complications and reduced mobility, particularly if longer prosthesis-free intervals are used

The Preoperative Microbial Detection is No Prerequisite for the Indication of Septic Revision in Cases of Suspected Periprosthetic Joint Infection

Aim of this study. Periprosthetic joint infections (PJIs) require a special antimicrobial regimen, fundamentally different from an aseptic treatment, making a correct preoperative diagnosis essential. However, a successful preoperative microbe detection is not always possible. We wanted to find out (1) if a preoperative microbe detection is a prerequisite before starting a septic revision in suspected PJIs or if the preoperative diagnosis can solely be based on (para) clinical signs (persistent CRP >1 mg/dl, early X-ray loosening signs in the first 5 years, leucocytes joint aspiration >1700/mu l, conspicuous history, and clinical signs like redness, pain, hyperthermia, swelling, and loss of function); (2) if patients with and without preoperative microbe detection have a different outcome; and (3) if the microbial growth is the most important criterion of a multifactorial PJI definition. Methods. We included all first-line two-stage hip (49) and knee (47) revisions, performed in our department from 06/2013 on, with an available 2-year follow-up. A PJI was defined as one of the following four criteria: fistula or purulence, Krenn Morawietz type 2 or 3, joint aspirate >2000/mu l leukocytes or >70% granulocytes, and microbial growth. This multifactorial PJI definition was based on the European Bone and Joint Infection Society (EBJIS). The standardized diagnostic algorithm is described in detail. Results. (1) 24 hip and 16 knee cases were treated without preoperative microbe detection solely on the basis of a (para) clinical diagnosis (see above). In the hip 91.6% (22 of 24 cases) showed an intraoperative microbe detection. In the knee, in 68.7% (11 of 16 cases) a microbe was detected intraoperatively and in 93.7% (15 of 16) at least one secure PJI criterion could be confirmed intraoperatively. (2) No statistical significant (p.517) difference between patients with (n = 56, reinfection rate 8.9%) and without (n = 40, 15%) preoperative microbe detection was found in a 2-year follow-up. (3) Microbial growth remains the overall (pre- and intraoperatively) most important criterion (hip 95.9%; knee 89.3%), followed by Krenn Morawietz for the intraoperative diagnosis (hip 67.3%, knee 48.9%), and joint aspiration for the knee and fistula for the hip, respectively, as preoperative criteria. Conclusion. High rates of intraoperatively fulfilled EBJIS PJI criteria show that a preoperative microbe detection is not necessary before intervening in suspected PJIs. The indication for a septic revision can solely be based on (para) clinical signs. The new established diagnostic algorithm based on a multifactorial PJI definition showed high precision in finding PJIs

Prediction of time to prosthesis implantation as a function of joint anatomy in patients with developmental dysplasia of the hip

BACKGROUND: Developmental dysplasia of the hip (DDH) can lead to pain and premature secondary osteoarthritis at an early stage. Joint-preserving osteotomy is an established solution to this problem. In contrast, a conservative approach would result in pain persistence, ultimately raising the patients question for a possible date of expected prosthesis implantation. The aim of the study was to identify the relationship between the dysplastic hip anatomy and the time of prosthesis implantation in order to enable prognostic predictions in younger patients with symptomatic DDH. MATERIALS AND METHODS: Data from 129 hips who received THA due to secondary DDH osteoarthritis were evaluated. The preoperative hip anatomy was evaluated for AI and LCE angle. Multiple linear regression analyses were then used to correlate the influence of these parameters with the patient's age at the time of surgery. In addition, a graphical relationship was derived by the method of power least squares curve fitting with second-degree polynomials. RESULTS: The mean age for THA was 54.3 ± 11 years. The time of surgery correlated significantly with LCE (0.37) and AI (- 0.3) (p < 0.001). The mean age of patients with LCE angle ≤ 10° was 41.9 ± 14.0 years, for LCE 11-20° 52.7 ± 9.5 years, and for LCE 21-30° 57.0 ± 10.3 years. The following formula could then be determined for the calculation of the potential patient age at the time of THA as a function of LCE angle: age pTHA = 40.2 + 0.8 × LCE angle - 0.01 × (LCE angle)2. CONCLUSION: A significant correlation between the extent of dysplasia and the time of prosthesis implantation was identified. In particular, the LCE and the AI correlated strongly with the time of implantation. The more dysplastic the angles were, the sooner the THA was necessary. Using the calculations presented in this study, the probable age of prosthesis implantation can be prognosticated and included in a counseling session about treatment options for DD

Cerclages after Femoral Osteotomy Are at Risk for Bacterial Colonization during Two-Stage Septic Total Hip Arthroplasty Revision

Aims: In cases of a two-stage septic total hip arthroplasty (THA) exchange a femoral osteotomy with subsequent cerclage stabilization may be necessary to remove a well-fixed stem. This study aims to investigate the rate of bacterial colonization and risk of infection persistence associated with in situ cerclage hardware in two-stage septic THA exchange. Patients and Methods: Twenty-three patients undergoing two-stage THA exchange between 2011 and 2016 were included in this retrospective cohort study. During the re-implantation procedure synovial fluid, periprosthetic tissue samples and sonicate fluid cultures (SFC) of the cerclage hardware were acquired. Results: Seven of 23 (30%) cerclage-SFC produced a positive bacterial isolation. Six of the seven positive cerclage-SFC were acquired during THA re-implantation. Two of the seven patients (29%) with a positive bacterial isolation from the cerclage hardware underwent a THA-revision for septic complications. The other five patients had their THA in situ at last follow-up. Conclusions: Despite surgical debridement and antimicrobial therapy, a bacterial colonization of cerclage hardware occurs and poses a risk for infection persistence. All cerclage hardware should be removed or exchanged during THA reimplantation

Preoperative versus postoperative initiation of thromboprophylaxis following major orthopedic surgery: safety and efficacy of postoperative administration supported by recent trials of new oral anticoagulants

In European countries, low-molecular-weight heparin is generally initiated preoperatively for thromboprophylaxis in hip or knee replacement surgery. The objective of this review is to compare pre- and postoperative thromboprophylaxis strategies using available evidence, and discuss the challenges and issues that arise. Surgery is the first step in the process of thrombus formation, but thrombosis is not an instant process and the formation and growth of the thrombus can take several days or weeks. Hence, it may be possible to stop this process if thromboprophylaxis is initiated after surgery. Meta-analyses or systematic reviews comparing pre- and postoperative initiation of therapy have found no consistent differences in efficacy and similar safety (bleeding rates) between the two strategies. The recently available oral anticoagulant dabigatran etexilate provides thromboprophylaxis when administered postoperatively and is as safe as preoperative enoxaparin. Further support for the use of postoperative oral thromboprophylaxis in hip or knee replacement surgery has been provided by the phase III clinical trials of rivaroxaban and apixaban versus preoperative enoxaparin. Postoperative thromboprophylaxis offers the opportunity to change management practices in Europe. As postoperative initiation may have a clinical benefit in some settings (e.g. for neuraxial anesthesia) and practical advantages (e.g. allowing same-day admission), it is a worthwhile thromboprophylactic strategy for hip or knee replacement surgery

Injectable autologous chondrocyte implantation (ACI) in acetabular cartilage defects—three-year results

To evaluate the clinical outcome after arthroscopic matrix-associated injectable autologous chondrocyte implantation (ACI) in patients with large full-thickness acetabular cartilage defects. ACI was performed in young patients with full-thickness acetabular cartilage defects >= 2 cm(2) in a two-step arthroscopic procedure. The patients were followed closely with clinical examinations and pre- and postoperative scores. The modified Harris Hip Score (mHHS), iHOT33 questionnaire (iHOT33) and the Subjective Hip Value (SHV) were surveyed. Demographic patient data was evaluated for influencing factors for the pre- and postoperative results. Thirty-two consecutive cases (4 female, 28 male, mean age 33 years) were included. The average defect size was 4.9 (range: 2-6) cm(2). They were followed at 6, 12, 24 and 36 months postoperatively. Patients had improved significantly from 64 to 91 points (P < 0.001) in the mHHS, from 44% to 86% (P < 0.001) in the iHOT33 and from 54% to 87% (P < 0.001) in the SHV. No surgery related complications were noted. Cell cultivation failed in two cases (7%) and the patients decided for a repeated harvesting of cartilage cylinders followed by a successful ACI. Patients age and size of the cartilage defect showed no significant correlation with the pre- or postoperative results. Injectable ACI is a reliable procedure treating full-thickness acetabular cartilage defects leading to promising results 3 years postoperatively with a significant increase in all scores despite large acetabular cartilage defects in the weight-bearing zone

An Early Transcriptional Analysis of Fracture Hematoma in Rat

Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole- genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone

Diverse expression of selected cytokines and proteinases in synovial fluid obtained from osteoarthritic and healthy human knee joints

BACKGROUND: Osteoarthritis (OA) is defined by signs and symptoms of inflammation within the affected joint. The aim of this study is to determine the mRNA expression levels of selected cytokines and matrix-metalloproteinases of cells found in synovial fluid (SF) obtained from osteoarthritic knee joints compared to healthy controls. METHODS: SF was obtained from 40 patients undergoing total knee arthroplasty due to evident OA and from 10 healthy controls. Expression of TNF-α, IL-1β, MMP-1 and MMP-3 was assayed among both groups by performing qPCR. Patients were configured concerning age, gender and BMI. RESULTS: IL-1β, MMP-1 and MMP-3 showed significantly higher expression among the OA group compared to control (P < 0.001). Strong correlation appeared between expression of MMP-1 and MMP-3 among OA patients (r = 0.856); no correlation was found between age, gender or BMI and cytokine/proteinase expression. Expression of IL-1β, MMP-1 and MMP-3 within SF was elevated in OA-patients. CONCLUSION: Consequently, cells within SF expressing cytokines and proteinases may play a relevant role in the progression of joint destruction. Considering the fact that SF in an OA joint comprises abnormal amounts of detrimental bioactive proteins, temporary clearance, dilution or suppression/modulation by means of lavage or disease-modifying medication may be promising to constitute interim relief or even postpone disease progression due to decreased inflammatory and/or degrading activity within the articular environment