Septic Failure After One-Stage Exchange for Prosthetic Joint Infection of the Hip: Microbiological Implications.

BACKGROUND: The microbiological implications of septic failure after 1-stage exchange for prosthetic joint infection (PJI) of the hip remain unclear. METHODS: Information was gathered on comorbidities, previous procedures, preoperative and postoperative microbiology results, methods of detection, and antibiotic resistance patterns, for all patients, who developed septic failure after 1-stage exchange for PJI of the hip performed at our institution during 2001-2017. RESULTS: Seventy-seven patients were identified. Septic failure was diagnosed a mean of 1.7 (standard deviation 2.3, range 0-11.8) years later. Although the spectrum of microorganisms was similar to preoperative, in the majority of patients (55%), the initial microorganism(s) was (were) replaced by (a) totally different microorganism(s). Overall, there was a decrease in the number of polymicrobial PJIs. The number of patients with high virulent microorganisms decreased significantly from 52 to 36 (P = .034). The number of PJIs due to gram-negative pathogens remained similar (11 vs 14, P = .491). The number of rifampicin-resistant staphylococci, fluoroquinolone-resistant streptococci, enterococci, and fungi changed from 8 to 15, 0 to 2, 7 to 3, and 1 to 2, respectively, but these changes did not reach statistical significance. CONCLUSION: The majority of reinfections is caused by different infecting bacteria, hence it is essential to perform a new diagnostic workup and not base treatment decisions (solely) on historical cultures. We were furthermore unable to irrefutably prove that, from a microbiological point of view, septic failure after 1-stage exchange comes with increased challenges. Given the time interval to failure, we propose that a longer follow-up of these patients is needed, than previously suggested.

Improved treatment strategies can result in better outcomes following one-stage exchange surgery for MRSA periprosthetic joint infection.

Introduction. Periprosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA-PJIs) are rare, with only a few studies reporting the treatment outcomes and even fewer reporting outcomes with one-stage exchange.Aim. This study aims to analyse the outcomes of one-stage exchange in the management of MRSA-PJIs.Methodology. Patients with MRSA-PJI of the hip and knee, who were treated with a one-stage exchange between 2001 and 2018 were enrolled in this study. The final cohort comprised of 29 patients, which included 23 hips and six knees. The mean follow-up was 5.3 years (1-9 years). Reinfection and complications rates after the one-stage exchange were analysed.Results. Overall infection control could be achieved in 93.1 % (27 out of 29 patients). The overall revision rate was 31.0% (9 patients), with three patients requiring an in-hospital revision (10.3 %). Six patients had to be revised after hospital discharge (20.7 %). Of the two reinfections, one had a growth of MRSA while the other was of methicillin-sensitive Staphyloccocus epidermidis.Conclusion. One-stage exchange surgery using current techniques could improve surgical outcomes with excellent results in the management of MRSA-PJIs.

Periprosthetic joint infection caused by anaerobes. Retrospective analysis reveals no need for prolonged cultivation time if sensitive supplemented growth media are used.

BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI) culture media and incubation time are controversially discussed, especially if anaerobic bacteria are the causative agent. This study was conducted to demonstrate the influence of sensitive supplemented growth media on the duration of culturing anaerobes. METHODS: Twenty-five consecutive cases were included in this retrospective study. For definition of PJI, the criteria of the Musculoskeletal Infection Society (MSIS) were considered. Histopathological analysis was interpreted according to the classification by Krenn et al. The quantity and time to positivity of detected anaerobes were monitored. Furthermore, antimicrobial activity within the tissue and sonicate fluid was phenotypically tested. RESULTS: In all cases, even if the patients had received antibiotics before recovery, culture of anaerobes (Propionibacterium species, Finegoldia magna, Parvimonas micra and Robinsoniella peoriensis), both from tissue samples and prosthetic components, first became detectable in supplemented liver thioglycollate broth within six days (median: four days). CONCLUSION: Recommendations for prolonged cultivation for up to 14 days mostly aim at detection of anaerobes. Here we present a laboratory procedure that can shorten cultivation time considerably.

The Accuracy of the Alpha Defensin Lateral Flow Device for Diagnosis of Periprosthetic Joint Infection: Comparison with a Gold Standard.

BACKGROUND: Alpha defensin is a new biomarker that has been shown to have a very high accuracy to rule out periprosthetic joint infection. Recently, a new rapid lateral flow version of the alpha defensin test was developed and introduced to detect high levels of alpha defensin in synovial fluid quickly and with ease. We conducted a single-center prospective clinical study to compare the results of the Synovasure Alpha Defensin Test with those of the Musculoskeletal Infection Society (MSIS) criteria, which are considered to be the gold standard for diagnosing periprosthetic joint infection. METHODS: A total of 223 consecutive patients with pain after total hip arthroplasty or total knee arthroplasty were enrolled into the study. In all patients, blood C-reactive protein was measured and joint aspirations were performed. From the synovial fluid, a leukocyte cell count with granulocyte percentage, microbiology cultures, and leukocyte esterase tests were carried out according to the recommendation of the MSIS for diagnosing periprosthetic joint infection. Concurrently, the Synovasure Alpha Defensin Test with a lateral flow device was performed from the aspirate. In the final clinical and statistical evaluation, 191 subjects with 195 joint aspirations (96 hips and 99 knees) were included. According to the MSIS criteria, there were 119 joints with an aseptic revision and 76 joints with periprosthetic joint infection. RESULTS: After statistical analysis, the overall sensitivity of the Synovasure Alpha Defensin Test was 92.1% (95% confidence interval [CI], 83.6% to 97.1%), the specificity was 100% (95% CI, 97.0% to 100%), the positive predictive value was 100% (95% CI, 94.9% to 100%), and the negative predictive value was 95.2% (95% CI, 89.9% to 98.2%). The overall accuracy of the Synovasure test was 96.9% (95% CI, 93.4% to 98.9%), 189 of 195 cases. CONCLUSIONS: Our results suggest that the Synovasure periprosthetic joint infection test has a very high accuracy in diagnosing periprosthetic infections after total hip arthroplasty or total knee arthroplasty. Although the Synovasure Alpha Defensin Test does not provide information on the identity of the infectious pathogen, the test does have an important role in recognizing periprosthetic joint infection early and enables surgeons to start proper therapy without delay. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Are There Benefits In Early Diagnosis Of Prosthetic Joint Infection With Multiplex Polymerase Chain Reaction?

Purpose Identification of bacteria and susceptibility are fundamental in periprosthetic joint infection (PJI). Especially in the case of systemic inflammatory response syndrome (SIRS) rapid detection of pathogens is essential for proper therapy. Bacterial cultures are time consuming. The polymerase chain reaction (PCR) is a non-culture molecular method and is able to rapidly identify pathogens and their resistance genes. Multiplex PCR (mPCR) can amplify several different DNA sequences simultaneously. The aim of this study was to show the value of mPCR for early diagnosis of PJI. Methods 60 patients undergoing total hip or knee revisions were recruited in this prospective single-centre-study. Three groups were created: 26 patients with aseptic loosening (negative control), 26 patients with chronic PJI, and 8 patients with acute PJI/SIRS. We compared the results of joint aspirates obtained intraoperatively investigated by mPCR with the microbiology results of tissue specimens. Results The overall sensitivity of mPCR was 78.8% (95% CI, 61.1 - 91.0%), the specificity was 100% (95% CI, 87.2 - 100%), the negative predictive value was 79.4% (95% CI, 62.1 - 91.3%), the positive predictive value was 100% (95% CI, 86.8 - 100%), and the overall accuracy was 88.3% (95% CI, 77.4 - 95.2%). The overall accuracy in acute infections/SIRS (87.5%) was greater than in late chronic PJI (76.9%). In PJI the mPCR was able to provide the results within 5 hours whereas the mean time for cultures was 6.4 days. Conclusions Multiplex PCR is a reliable diagnostic tool in PJI management, especially in acute cases complicated with SIRS. Early diagnosis within several hours is possible, targeted antibiotic treatment can be started promptly.

Limitations in the use of PSMγ, agr, RNAIII, and biofilm formation as biomarkers to define invasive Staphylococcus epidermidis from chronic biomedical device-associated infections.

Staphylococcus epidermidis is a common cause of biomedical device-associated infections. Agr is the major quorum sensing system in staphylococci and regulates virulence factors. Four agr-specificity groups exist in S. epidermidis, and chronic S. epidermidis infections are hypothesised to select for agr-negative phenotypes. Therefore, we investigated S. epidermidis strains from prosthetic joint- and catheter-associated infections to establish i) whether an infection selects for an agr-negative phenotype; ii) the importance of PSMγ and iii) if the agr-specificity group is infection dependent. S. epidermidis nasal isolates from healthy volunteers were used as controls. The distribution of agr-specificity groups was significantly different between infection and control episodes, but did not distinguish between the infection types. PSMγ secretion was used to determine agr-activity and HPLC analysis showed that 44% of prosthetic and 32% of catheter-associated episodes produced no PSMγ in comparison to 8% of the control strains. However, PSMγ expression did not always correlate with RNAIII up-regulation, indicating that PSMγ synthesis is likely influenced by additional post-transcriptional control. The data suggests chronic S. epidermidis infections favour agr-specificity group 1 but the results suggest that they do not select for an agr-negative phenotype. Further studies are required to explore the mechanisms underlying the selection and survival of these S. epidermidis phenotypes isolated from biomedical device-associated infections.

A Standardized Regimen for the Treatment of Acute Postoperative Infections and Acute Hematogenous Infections Associated With Hip and Knee Arthroplasties.

BACKGROUND: Papers concerning the treatment of periprosthetic infections and acute hematogenous infections often concern inhomogeneous treatment concepts or low numbers of patients; this results in inconsistent rates of treatment success. METHODS: Thirty-nine patients with early periprosthetic infections and 28 patients with acute hematogenous infections were treated with a homogeneous concept and followed with a mean period of 41.8 (24-132) months in order to investigate the success rate and influencing factors. All patients were treated with open surgical debridement, a revision of all removable components and irrigation with an antiseptic solution (octinedine). All patients received a systemic vancomycin/rifampicin antibiotic therapy until the microorganism causing the infection could be identified; a specific antibiotic therapy then followed until the end of the sixth week. RESULTS: This unified treatment regimen resulted in an overall success rate of 71.6%, an 82.1% success for early infections and 57.1% for acute hematogenous infections. Variables that influenced the recurrence of an infection were the timespan between revision and first appearance of symptoms (<2 days), the number of previous operations, the American Society of Anesthesiologists classification, and nicotine abuse. CONCLUSION: It appears that, in cases of early postoperative infection, a reproducibly high rate of success in retaining an implant can be achieved with this specific therapy regime if surgical intervention can be carried out within 2 days of first symptoms.

Algorithm to Diagnose Delayed and Late PJI: Role of Joint Aspiration.

Total Joint Arthroplasty (TJA) continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. A devastating complication after TJA is infection. Periprosthetic joint infection (PJI), represents one of the major causes of failure and remains a significant challenge facing orthopaedics today. PJI usually requires additional surgery including revision of the implants, fusion or amputations causing tremendous patient suffering but also a heavy health economics burden. PJI is at the origin of around 20-25 % of total knee arthroplasty (Bozic et al. 2010; de Gorter et al. 2015; Sundberg et al. 2015) and 12-15 % of total hip arthroplasty (Bozic et al. 2009; Garellick et al. 2014; de Gorter et al. 2015) failures.

Robinsoniella peoriensis, originally isolated from swine manure, and early periprosthetic hip infection: Case report and review of the literature.

We report on the first case of a periprosthetic joint infection with the anaerobic spore-forming Gram-positive rod Robinsoniella peoriensis as the causative agent. The bacterium was first isolated from a swine manure storage pit and has so far rarely been associated with human infections.

Lyophilized allogeneic bone tissue as an antibiotic carrier.

The rising number of primary joint replacements worldwide causes an increase of revision surgery of endoprostheses due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome and the use of antibiotic-impregnated bone grafts might control the infection and give a good support for the implant. In this study we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. Lyophilized bone chips and fresh frozen bone chips were mixed with gentamicin sulphate, gentamicin palmitate, vancomycin, calcium carbonate/calcium sulphate impregnated with gentamicin sulphate, and calcium carbonate/calcium sulphate bone substitute material impregnated with vancomycin. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B. subtilis, S. aureus and methicillin-resistant Staphylococcus aureus. The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during all the experimental time. That fact might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high in the first and second day, decreasing and keeping a low rate until the end of the second week. Depending on the surgical strategy either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within two weeks after surgery. In case of uncemented revision of joint replacements allogeneic bone is able to deliver therapeutic doses of gentamicin and peak levels immediately after implantation during a fortnight. The use of lyophilized and fresh frozen bone allografts as antibiotic carriers is recommended for prophylaxis of bone infection.

Bioavailability of gentamicin and vancomycin released from an antibiotic containing bone cement in patients undergoing a septic one-stage total hip arthroplasty (THA) revision: a monocentric open clinical trial.

BACKGROUND: The purpose of this clinical investigation was to evaluate the systemic bioavailability of antibiotics from bone cement after implantation. This was done by determining the concentrations of gentamicin and vancomycin in plasma and urine of patients receiving a novel bone cement during one-stage revision in periprosthetic hip infections. The local concentrations of both antibiotic agents in wound exudate as well as the efficacy and tolerability were assessed as a secondary objective. METHODS: In a prospective open clinical trial, 20 patients (mean age 62.5 years) with an implanted hip prosthesis requiring revision due to periprosthetic infection were treated with this antibiotic loaded bone cement (ALBC) between 2009 and 2011. The concentrations of gentamicin and vancomycin in plasma, urine and wound exudate were determined with quantitative liquid chromatography analysis (LC-MS-MS). RESULTS: The mean postoperative maximum gentamicin plasma concentration at 5.85 hours was 209.65 ng/mL. For vancomycin, a mean postoperative maximum plasma concentration of 134.64 ng/mL was determined at 20.03 hours. Small amounts of both antibiotics were excreted via the urine within the first 10 days after surgery. No reinfection was observed at the end of the hospital stay or during the follow-up period up to 7 months post surgery. CONCLUSIONS: Slow absorption of both antibiotics after release from the cement resulted in plasma concentrations well below toxic levels and did not result in a critical systemic concentration potientially inducing bacterial resistance. The treatment with this novel bone cement was assessed as efficacious and was very well tolerated by all patients.

Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a.

BACKGROUND: A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI). METHODS: This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI. RESULTS: Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms. CONCLUSIONS: These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI.

Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern.

We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-ß, IL-2, IL-6, IL-8, IL-10, IL17, and TGFß). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

Fungal periprosthetic joint infection in total knee arthroplasty: a systematic review.

Fungal periprosthetic joint infection (PJI) is a rare but devastating complication following total knee arthroplasty (TKA). A standardized procedure regarding an accurate treatment of this serious complication of knee arthroplasty is lacking. In this systematic review, we collected data from 36 studies with a total of 45 reported cases of a TKA complicated by a fungal PJI. Subsequently, an analysis focusing on diagnostic, medicaments and surgical procedures in the pre-, intra- and postoperative period was performed. Candida spp. accounts for about 80% (36 out of 45 cases) of fungal PJIs and is therefore the most frequently reported pathogen. A systemic antifungal therapy was administered in all but one patient whereas a local antifungal therapy, e.g. the use of an impregnated spacer, is of inferior relevance. Resection arthroplasty with delayed re-implantation (two-stage revision) was the surgical treatment of choice. However, in 50% of all reported cases the surgical therapy was heterogeneous. The outcome under a combined therapy was moderate with recurrent fungal PJI in 11 patients and subsequent bacterial PJI as a main complication in 5 patients. In summary, this systematic review integrates data from up to date 45 reported cases of a fungal PJI of a TKA. On the basis of the current literature strategies for the treatment of this devastating complication after TKA are discussed.

Fungal periprosthetic joint infection of the hip: a systematic review.

Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty with an incidence of approximately 1%. Due to the high risk of persisting infection, successful treatment of fungal PJI is challenging. The purpose of this study was to gain insight into the current management of fungal PJI of the hip and, by systematically reviewing the cases published so far, to further improve the medical treatment of this serious complication of total hip arthroplasty. Thus, we conducted a systematic review of the available literature concerning fungal PJI in total hip arthroplasty, including 45 cases of fungal PJI. At the moment a two-stage revision procedure is favorable and there is an ongoing discussion on the therapeutic effect of antifungal drug loaded cement spacers on fungal periprosthetic infections of the hip. Due to the fact that there is rare experience with it, there is urgent need to establish guidelines for the treatment of fungal infections of total hip arthroplasty.