Unexpected Positive Cultures in Hip and Knee Periprosthetic Fractures.

BACKGROUND: The purpose of this study was to determine the prevalence of unexpected positive cultures noted at the time of revision surgery for periprosthetic fracture (PPF) after total hip or knee arthroplasty. Moreover, we evaluated whether this finding should be considered clinically significant and what type of treatment, if any, was required. METHODS: This was a single-center retrospective review of 270 patients undergoing surgery for PPFs from December 2010 to December 2021. Exclusion criteria included: open fractures; history of infection at fractured joint; non-operatively treated patients; and intraoperative fractures. The primary end point was the prevalence of unexpected positive cultures noted at the time of revision surgery. This was defined as one or more positive cultures in a PPF that the surgeon had preoperatively classified as aseptic according to the 2018 International Consensus Meeting. Data collection included patient demographics, medical histories, preoperative investigations, postoperative microbiology, and treatment. RESULTS: During the study period, 159 patients were admitted with PPFs of the hip and 61 with PPFs of the knee. The mean age was 70 years (range, 32 to 93 years). Unexpected positive cultures were diagnosed postoperatively in 15 patients (6.8%; 10 hips, 5 knees). The most prevalent organism was Staphylococcus epidermidis (35.0%). Of those 15 patients, 6 required a surgical revision for infection. None of the patient-related risk factors were found to be associated with an increased risk of unexpected positive cultures. The comparison between infected and noninfected patients showed a significant association between preoperative C-reactive protein >10 mg/mL (P = .04), loose implant (P = .07), and infection. CONCLUSIONS: The prevalence of unexpected positive cultures was 6.8% in our study cohort. Although surgical treatment may be required, the majority of patients seem to require no treatment. Larger series are required to investigate the clinical importance of this rare finding. LEVEL OF EVIDENCE: III.

The Mark Coventry Award: PhotothermAA Gel Combined With Debridement, Antibiotics, and Implant Retention Significantly Decreases Implant Biofilm Burden and Soft-Tissue Infection in a Rabbit Model of Knee Periprosthetic Joint Infection.

BACKGROUND: Chronic periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. The underlying pathogenesis often involves the formation of bacterial biofilm that protects the pathogen from both host immune responses and antibiotics. The gold standard treatment requires implant removal, a procedure that carries associated morbidity and mortality risks. Strategies to preserve the implant while treating PJI are desperately needed. Our group has developed an anti-biofilm treatment, PhotothermAA gel, which has shown complete eradication of 2-week-old mature biofilm in vitro. In this study, we tested the anti-biofilm efficacy and safety of PhotothermAA in vivo when combined with debridement, antibiotics and implant retention (DAIR) in a rabbit model of knee PJI. METHODS: New Zealand white rabbits (n = 21) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) after capsule closure. At 2 weeks, rabbits underwent sham surgery (n = 6), DAIR (n = 6), or PhotothermAA with DAIR (n = 9) and were sacrificed 2 weeks later to measure implant biofilm burden, soft-tissue infection, and tissue necrosis. RESULTS: The combination of anti-biofilm PhotothermAA with DAIR significantly decreased implant biofilm coverage via scanning electron microscopy compared to DAIR alone (1.8 versus 81.0%; P < .0001). Periprosthetic soft-tissue cultures were significantly decreased in the PhotothermAA with DAIR treatment group (log reduction: Sham 1.6, DAIR 2.0, combination 5.6; P < .0001). Treatment-associated necrosis was absent via gross histology of tissue adjacent to the treatment area (P = .715). CONCLUSIONS: The addition of an anti-biofilm solution like PhotothermAA as a supplement to current treatments that allow implant retention may prove useful in PJI treatment.

Unexpected positive cultures in revision total knee arthroplasty after unicompartmental knee arthroplasty.

PURPOSE: Unexpected positive cultures are defined as a single positive culture in intraoperative samples taken during revision surgery after prosthetic joint infection was preoperatively ruled out. This study aims to determine the prevalence of unexpected positive cultures (UPC) in revision total knee arthroplasty (TKA) after unicompartmental knee arthroplasty (UKA). As a secondary objective, this study aims to compare the re-intervention rate in this specific group, between UPC and non-UPC patients. The hypothesis is that the UPC prevalence in patients who undergo a revision TKA after UKA is not higher than in other TKA revision cases and this does not increase the risk of re-intervention. METHODS: This is a retrospective study where all patients who underwent a UKA revision from January 2016 to February 2023 in a high-volume arthroplasty centre, were analyzed. Unexpected positive culture prevalence in this group of patients was obtained. RESULTS: During the included period, 270 UKA revision surgeries were performed. Eight cases had at least two positive cultures and were therefore excluded. The final analysis included 262 patients. Of these, 8 (3.05%) patients presented UPCs and the isolated microorganisms were low-virulence organisms. None of the UPC patients received any treatment. No statistical differences were found between UPC and non-UPC groups in the analyzed variables. CONCLUSION: The prevalence of unexpected positive cultures in patients following revision of unicompartmental knee arthroplasty is lower than in patients who undergo a revision of total knee arthroplasty. In UKA patients a UPC does not seem to increase the risk of a re-intervention, so it can be safely ignored if ICM criteria are not met.

Differing Microorganism Profile in Early and Late Prosthetic Joint Infections Following Primary Total Knee Arthroplasty - Implications for Empiric Antibiotic Treatment.

BACKGROUND: Prosthetic joint infection (PJI) is the leading cause of revision following total knee arthroplasty (TKA). Prior to microorganism identification, the choice of the correct empiric antibiotics is critical to treatment success. This study aims to 1) compare the microorganism and resistance profile in early and late PJIs; 2) recommend appropriate empiric antibiotics. METHODS: A multicentre retrospective review was performed over a 15-year period. First episode PJIs were classified by both the Tsukayama Classification and Auckland Classification. For each PJI case, the causative organism and antibiotic sensitivity were recorded. RESULTS: Of eligible patients, 232 culture-positive PJI cases were included. Using either classification system, early PJIs (<4 weeks or <1 year since primary) were significantly more likely to be resistant and polymicrobial. The predominant organisms were coagulase-negative Staphylococci in early PJIs while Staphylococcus aureus was the most common in late PJIs. The distribution of gram-negative cases was higher in early Class-A than late Class-C PJIs (25% versus 6%, P = .004). Vancomycin provided significantly superior coverage when compared to Flucloxacillin for early infections, and addition of a gram-negative agent achieved coverage over 90% using both classification systems. CONCLUSION: Based on the microbiological pattern in Tsukayama criteria, Vancomycin with the consideration of Gram-negative agent should be considered for Class-A infections given the high proportion of resistant and polymicrobial cases. For Class-C infections, Cephazolin or Flucloxacillin is likely sufficient. We recommend antibiotics to be withheld in Class-B infections until cultures and sensitivities are known.

Intra-wound vancomycin powder for the eradication of periprosthetic joint infection after debridement and implant exchange: experimental study in a rat model.

BACKGROUND: Intra-wound vancomycin powder (VP) has been used in clinical practice to prevent periprosthetic joint infection (PJI) after primary knee/hip arthroplasty. The role of intra-wound VP in the setting of debridement and implant exchange after PJI remains undefined. This study aimed to explore the efficacy and safety of intra-wound VP in the control of methicillin-resistant S. aureus (MRSA) infection after debridement and implant exchange. METHODS: PJI modeling by knee prosthesis implantation and MRSA inoculation, debridement and implant exchange were performed in Wistar rats successively to mimic the one-stage exchange arthroplasty of PJI patients. Two weeks of systemic vancomycin (SV) or/and intraoperative intra-wound VP of single dosage were applied after revision surgery. RESULTS: No post-surgery deaths, incision complications and signs of drug toxicity were observed. The microbial counts of SV or intra-wound VP group were significantly reduced compared with the control group, while bacteria were still detected on the bone, soft-tissue and prosthesis. The elimination of bacterial counts, along with improvement of tissue inflammation and serum inflammatory markers, were observed in the rats with SV plus intra-wound VP. Serum levels of vancomycin in all groups were lower than that of causing nephrotoxicity, while no statistic difference was observed in the serum biochemical marker among the groups. CONCLUSIONS: Intra-wound VP is effective after debridement and implant exchange in our current rat PJI model. Neither SV nor intra-wound VP alone could eradicate the bacteria within a two-weeks treatment course, while SV plus intra-wound VP could eliminate the MRSA infection, without notable hepatic or renal toxicity and any incision complications.

Low prevalence of tissue detection of cefepime and daptomycin used as empirical treatment during revision for periprosthetic joint infections: results of a prospective multicenter study.

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprosthetic joint infection operated with one- or two-stage replacement during which cefepime (2g)-daptomycin (10mg/kg) combination was administered intravenously as intraoperative empirical antibiotic treatment. Three biopsies (two bones and one synovial membrane) were taken from each patient just before the insertion of the new implant. Eighteen adults of median age 68 years were included. Knee was involved in 10 patients (55.6%) and surgery consisted in one-/two-stage replacement in 11/7 patients. A tourniquet was used during the intervention in the 10 patients with knee prosthesis. Among 54 tissue samples, cefepime and daptomycin were detected respectively in 35 (64.8%) and 21 (38.9%) cases (P=0.01). A total of 17 bacteria dominated by staphylococci (n=14) were identified in 10 patients; tissue inhibitory quotient calculated in 51 samples was >1 in 22 cases (43.1%) for cefepime and in 16 cases (31.4%) for daptomycin. The proportion of tissue samples with detectable antibiotic was significantly higher in hip versus knee prosthesis (P=0.03). The present study suggests that intraoperative empirical administration of cefepime-daptomycin combination during septic prosthetic joint replacement results in a high proportion of tissue samples in which at least one of the two antibiotics was not detected or at a low concentration despite satisfactory concomitant blood serum concentrations.

Is EDTA Irrigation Effective in Reducing Bacterial Infection in a Rat Model of Contaminated Intra-articular Knee Implants?

BACKGROUND: To mitigate the possibility of infection after arthroplasty, intraoperative irrigation is essential to remove contaminating bacteria. Previous studies have demonstrated that irrigation with an EDTA solution before wound closure is superior to irrigation with normal saline in removing contaminating bacteria in a rat model of open fractures. However, the effectiveness of an EDTA solution in a model with a contaminated intra-articular implant remains unclear. QUESTIONS/PURPOSES: (1) Does irrigation with an EDTA solution decrease the proportion of culture-positive joints compared with normal saline, benzalkonium chloride, and povidone iodine? (2) Is an EDTA solution toxic to cells resident in joints including chondrocytes, osteoblasts, and synovial fibroblasts? (3) Does irrigation with an EDTA solution have adverse effects including arthrofibrosis and hypocalcemia? METHODS: We first established a model of contaminated intra-articular implants. Female Sprague-Dawley rats (n = 30 for each treatment group) underwent knee arthrotomy and implantation of a femoral intramedullary wire with 1 mm of intra-articular communication. To simulate bacterial contamination, the inserted wire was inoculated with either Staphylococcus aureus or Escherichia coli. After 1 hour, the wound and implant were irrigated with normal saline, benzalkonium chloride, povidone iodine, or an EDTA solution (1 mM). The animals were euthanized 1 week later, and the distal femur, knee capsule, and implanted wire were harvested for bacterial culture using standard techniques. In this study, we used a well-established animal model of an intra-articular implant and inoculated the implant to simulate the clinical setting of intraoperative contamination. The proportion of culture-positive joints in normal saline, benzalkonium chloride, povidone-iodine, and EDTA groups were compared. The viable cell numbers (chondrocytes, osteoblasts, and synovial fibroblasts) were counted and compared after treatment with either solution. Measurement of blood calcium level and histological examination of the joint were performed to rule out hypocalcemia and arthrofibrosis after EDTA irrigation. RESULTS: With S. aureus inoculation, EDTA irrigation resulted in fewer culture-positive joints than normal saline (37% [11 of 30] versus 70% [21 of 30]; p = 0.019), benzalkonium chloride (83% [25 of 30]; p < 0.001), and povidone iodine (83% [25 of 30]; p < 0.001) irrigation. Likewise, infection rates for implant inoculation with E. coli were also lower in the EDTA irrigation group (13% [four of 30]) than in the normal saline (60% [18 of 30]; p < 0.001), benzalkonium chloride (77% [23 of 30]; p < 0.001), and povidone iodine (80% [24 of 30]; p < 0.001) groups. Between normal saline control and EDTA, there were no differences in cell viability in chondrocytes (normal saline: 98% ± 18%; EDTA: 105% ± 18%; p = 0.127), osteoblasts (normal saline: 102 ± 19%, EDTA: 103 ± 14%; p = 0.835), and synovial fibroblasts (normal saline: 101% ± 21%, EDTA: 110% ± 13%; p = 0.073). EDTA irrigation did not result in hypocalcemia (before irrigation: 2.21 ± 0.32 mmol/L, after irrigation: 2.23 ± 0.34 mmol/L; p = 0.822); and we observed no arthrofibrosis in 30 histologic samples. CONCLUSIONS: In a rat model of a bacteria-contaminated intra-articular implants, intraoperative irrigation with 1 mmol/L of an EDTA solution was superior to normal saline, 0.03% benzalkonium chloride, and 0.3% povidone iodine in preventing surgical-site infection and caused no adverse effects including death of resident cells, arthrofibrosis, and hypocalcemia. Future studies should seek to replicate our findings in other animal models, perhaps such as dog and goat. CLINICAL RELEVANCE: If other animal models substantiate the efficacy and safety of the EDTA solution, clinical trials would be warranted to determine whether the use of an EDTA irrigation solution might reduce the risk of periprosthetic joint infections in patients compared with traditional irrigation solutions.

Influence of retrieved hip- and knee-prosthesis biomaterials on microbial detection by sonication.

Microorganisms' ability to adhere and form a biofilm differs among biomaterials; however, clinical data are conflicting. Microbial adherence and biofilm formation on different biomaterials of explanted joint prosthesis components were investigated. Consecutive patients with explanted joint prosthesis were prospectively included. The bacterial load dislodged from retrieved prosthetic components was evaluated qualitatively and quantitatively in sonication-fluid cultures. For comparison between groups, one-way ANOVA and Wilcoxon signed-rank test were used. A total of 112 components originating from 58 knee and 54 hip prostheses were retrieved from 40 patients. Components were made of titanium alloy in 42 cases, cobalt-chromium alloy in 38 and polyethylene in 32. Bacteria in sonication-fluid cultures grew in all polyethylene components (100 %), followed by titanium alloy (79 %) and cobalt-chromium components (71 %). Larger bacterial counts were found on polyethylene than on titanium (p < 0.013) or cobalt-chromium alloy (p = 0.028). Coagulase-negative Staphylococcus aureus and Streptococcus species were most commonly isolated. In conclusion, polyethylene showed larger biofilm burden than metal alloys, indicating their higher microbial adhesion affinity in vivo. Sonication of polyethylene liners, rather than the whole prosthesis, was sufficient for diagnosis of prosthetic joint infection. Moreover, bacterial counts were larger after sonication of polyethylene liners than of metal alloys, suggesting intrinsic differences in the ability for biofilm formation on various biomaterials. Polyethylene liners allowed the diagnosis of prosthetic joint infections (PJIs) in all investigated cases, suggesting that sonication of polyethylene liners rather than of the complete prosthesis was sufficient for pathogen detection in PJIs.

The use of labelled leucocyte scintigraphy to evaluate chronic periprosthetic joint infections: a retrospective multicentre study on 168 patients.

Labelled leucocyte scintigraphy (LS) is regarded as helpful when exploring bone and joint infections. The aim of this study was to evaluate the utility of LS for the diagnosis of chronic periprosthetic joint infections (PJIs) in patients exhibiting arthroplastic loosening. One hundred sixty-eight patients were referred to centres for treatment of complex PJI. One hundred fifty underwent LS using 99mTc-HMPAO (LLS); 18 also underwent anti-granulocyte scintigraphy (AGS) and 13 additional SPECT with tomodensitometry imaging (SPECT-CT). The LS results were compared with bone scan data. For all, the final diagnoses were determined microbiologically; perioperative samples were cultured. LS values were examined, as well as sensitivity by microorganism, anatomical sites, and injected activity. LS results were also evaluated according to the current use of antibiotics or not. The sensitivity, specificity, and positive predictive value of LLS were 72%, 60%, and 80%, respectively. LLS performed better than did AGS. SPECT-CT revealed the accurate locations of infections. The sensitivity of LS was not significantly affected by the causative pathogen or the injected activity. No correlation was evident between the current antibiotic treatment and the LS value. The test was more sensitive for knee (84%) than hip arthroplasty (57%) but was less specific for knee (52% vs. 75%). Sensitivity and specificity of LLS varied by the location of infection bone scan provide no additional value in PJI diagnosis. Current antibiotic treatment seems to have no influence on LS sensitivity as well as labelling leukocyte activity or pathogens responsible for chronic PJI.

Probabilistic chemotherapy in knee and hip replacement infection: the place of linezolid.

Prosthetic joint infection (PJI) can occur with a wide range of microorganisms and clinical features. After replacement surgery of prosthetic joint, prescription of probabilistic broad-spectrum antimicrobial therapy is usual, while awaiting microbial culture results. The aim of our study was to describe the antibiotic susceptibility of microorganisms isolated from hip and knee PJI. The data were collected to determine the best alternative to the usual combination of piperacillin-tazobactam (TZP) or cefotaxime (CTX) and vancomycin (VAN). Based on a French prospective, multicenter study, we analyzed microbiological susceptibility to antibiotics of 183 strains isolated from patients with confirmed hip or knee PJI. In vitro susceptibility was evaluated: TZP+VAN, TZP+linezolid (LZD), CTX+VAN, and CTX+LZD. We also analyzed resistance to different antibiotics commonly used as oral alternatives. Among the 183 patients with PJI, 62 (34%) had a total knee prosthesis, and 121 (66%) a hip prosthesis. The main identified bacteria were Staphylococcus aureus (32.2% of isolates), coagulase-negative staphylococci (27.3%), Enterobacteriaceae (14.2%), and Streptococcus (13.7%). Infections were polymicrobial for 28 (15.3%) patients. All combinations were highly effective: CTX+VAN, CTX+LZD, TZP+VAN, and TZP+LZD (93.4%, 94%, 98.4%, and 98.9% of all cases respectively). Use of LZD instead of VAN in combination with a broad-spectrum beta-lactam covers almost all of the bacteria isolated in PJI. This association should be considered in probabilistic chemotherapy, as it is particularly easy to use (oral administration and no vancomycin monitoring).

An unusual case of Erysipelothrix rhusiopathiae prosthetic joint infection from the Canadian Arctic: whole genome sequencing unable to identify a zoonotic source.

BACKGROUND: Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation. CASE PRESENTATION: We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6 weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case. CONCLUSIONS: Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.

Correlation of histological and microbiological findings in septic and aseptic knee implant failure.

INTRODUCTION: The Musculoskeletal Infection Society (MSIS) has defined specific clinical and laboratory criteria for the diagnosis of periprosthetic joint infection (PJI). In this study we assessed the diagnostic utility of MSIS microbiological and histological criteria for PJI in 138 cases of septic and aseptic knee implant failure. MATERIALS AND METHODS: Intra-operative samples from 60 cases of knee septic implant failure (SIF) and 78 cases of aseptic implant failure (AIF), defined on the basis of clinical, laboratory and operative findings/surgical management, were analysed microbiologically and histologically. Findings were correlated with the final clinical diagnosis and the specificity, sensitivity, accuracy, positive and negative predictive value of MSIS microbiological and histological criteria for knee PJI were assessed. RESULTS: 80% of SIF cases showed culture of the same organism from two or more samples (ie MSIS microbiological criteria for definite PJI); 8.3% grew an organism from one sample, and 11.7% showed no growth from any sample. 23.1% of AIF cases grew an organism from one sample and 76.9% showed no growth from any sample. MSIS histological criteria for PJI identified 96.7% of SIF cases. The sensitivity, specificity, accuracy and positive and negative predictive value of MSIS histological criteria for PJI were 96.7%, 100%, 98.6%, 100% and 97.5%, respectively. MSIS microbiological and histological criteria identified all AIF cases. CONCLUSIONS: Knee PJI is more often identified by current MSIS histological than microbiological criteria. A significant proportion of SIF cases show either no growth or growth of an organism from only one sample. AIF is identified by both MSIS microbiological and histological criteria. Correlation of clinical, radiological and laboratory findings is required for the diagnosis of knee PJI.

Inadequate evaluation and management of suspected -infections after TKA surgery in Lithuania: a retrospective study of 2,769 patients with 2-year follow-up.

Background and purpose - The evidence-based algorithms for treatment of periprosthetic joint infection (PJI) recommend surgical intervention in combination with the use of systemic antibiotics. However, still it is not unusual to treat total knee arthroplasty (TKA) patients with suspected infection using only antibiotics. We investigated treatment pathways for TKA patients with suspected infection in Lithuania. Patients and methods - Of the 4,069 TKA patients (4,269 knees) registered in the Lithuanian Arthroplasty Register (2013-2015) 2,769 patients (2,825 knees) were interviewed 2 years after the surgery. The patients were asked if they had been subject to antibiotic treatment after the TKA surgery and/or if any additional surgical interventions on the operated knee had been performed. The number of patients treated with antibiotics due to problems in the operated knee was identified and cumulative revision rates (CRR) were calculated. Results - 180 (7%) patients of the total 2,769 reported that they had been prescribed antibiotics after the primary TKA; 132 of these patients (70%) said they had received antibiotics due to problems with the operated knee. The 2-year CRR after TKA in patients not treated with antibiotics was 0.7% (95% CI 0.4-1), as compared with 24% (95% CI 17-32) in those who had used antibiotics due to the problems in the operated knee for more than 1 week. Interpretation - In Lithuania there seems to be a lack of adherence to evidence-based treatment guidelines when infection is suspected after primary TKA.

A comparative study of intraoperative frozen section and alpha defensin lateral flow test in the diagnosis of periprosthetic joint infection.

Background and purpose - For decision-making (aseptic vs. septic), surgeons rely on intraoperatively available tests when a periprosthetic joint infection (PJI) cannot be confirmed or excluded preoperatively. We compared and evaluated the intraoperative performances of the frozen section and the alpha defensin lateral flow test in the diagnosis of PJI. Patients and methods - In this prospective study, consecutive patients with indicated revision surgery after arthroplasty were included. Patients were classified as having PJI using the MusculoSkeletal Infection criteria. The presence of alpha defensin was determined using the lateral flow test intraoperatively. During revision surgery, tissue samples were harvested for frozen and permanent section. Analysis of diagnostic accuracy was based on receiver-operating characteristics. Results - 101 patients (53 hips, 48 knees) were eligible for inclusion. Postoperatively, 29/101 patients were diagnosed with PJI, of which 8/29 cases were definitely classified as septic preoperatively. Of the remainder 21 septic cases, the intraoperative alpha defensin test and frozen section were positive in 13 and 17 patients, respectively. Sensitivities of the alpha defensin test and frozen section were 69% and 86%, respectively. The area under the curves of both tests showed a statistically significant difference (p = 0.006). Interpretation - The frozen section showed a significantly higher performance compared with the alpha defensin test and a near perfect concordance with the definitive histology, and therefore remains an appropriate intraoperative screening test in diagnosing PJI. Although the sensitivity of the alpha defensin test was lower compared with that of frozen section, this test is highly specific for confirming the diagnosis of PJI.

Cost-benefit analysis of antibiofilm microbiological techniques for peri-prosthetic joint infection diagnosis.

BACKGROUND: Implant-related infections, including those of peri-prosthetic joint (PJIs), osteosynthesis and other biomaterials, are biofilm-related. Pathogen identification is considered the diagnostic benchmark; however, the presence of bacterial biofilms makes pathogen detection with traditional microbiological techniques only partially effective. To improve microbiological diagnostic accuracy, some biofilm debonding techniques have been recently proposed. Aim of this health economics assessment study was to evaluate their economic impact on hospital costs. METHODS: Direct and indirect hospital costs connected with the routine introduction of sonication and dithiothreitol treatment applied to hip and knee PJIs and of tissue cultures were examined. In particular the consequences of diagnostic inaccuracy, the opportunities, costs, and risks of each technique were calculated. RESULTS: Considering an average of five samples per patient, processed separately with traditional tissue culture with or without sonication of prosthetic components, or pooled together using the MicroDTTect device (a close system for sample collection, transport and treatment with Dithiothreitol for microbial release from biofilm), the overall mean direct cost per patient was € 397 and € 393 for sonication or MicroDTTect, respectively, compared to € 308 for traditional tissue cultures. In terms of opportunity costs, MicroDTTect was the most effective technique, allowing for a 35% or 55% reduction in time required for sample treatment, compared to tissue cultures combined or not with sonication, respectively. Pooling together direct and indirect costs associated with false positive and negative results of the different diagnostic techniques, unnecessary medical treatments and possible medical claims, MicroDTTect or sonication become increasingly cost-effective when the extra-costs, generated by diagnostic inaccuracy of traditional tissue culture, took place, respectively, in 2% or 20% or more of the patients. CONCLUSIONS: This is the first study specifically focused on the economic impact of the routine clinical use of microbiological antibiofilm sampling and processing techniques in orthopaedics. Although our results may suffer from a potential country and hospital bias, as the data collection process for direct and indirect costs is specific to each institution and country, this analysis highlights the potential economic advantage to hospitals associated with the routine introduction of antibiofilm techniques for microbiological diagnosis of PJI.

Culturing Periprosthetic Joint Infection: Number of Samples, Growth Duration, and Organisms.

BACKGROUND: Owing to the difficulty isolating microorganisms in periprosthetic joint infection (PJI), current guidelines recommend that 3-5 intraoperative samples be cultured and maintained for 3-14 days. We investigated (1) the optimal number of culture samples and growth duration to diagnose PJI and (2) the microbiology profile at our institution. METHODS: A retrospective review of 711 patients (329 hips, 382 knees) with PJI that met Musculoskeletal Infection Society criteria from 2000 to 2014 was performed. Two thousand two hundred ninety aerobic and anaerobic cultures were analyzed. A manual chart review collected demographic, surgical, and microbiological data. Microbiology profiles were trended. Logistic regression analysis was performed to determine statistical significance. RESULTS: Obtaining 5 samples provided the greatest yield positive cultures for diagnosing PJI. The percentage of positive cultures overall was 62.6% and stratified by organism type: antibiotic resistant (80.0%), Staphylococcus aureus (76.0%), gram negative (58.9%), Pseudomonas (52.0%), variant PJI organisms (28.2%), Propionibacterium acnes (20.0%), and Escherichia coli (8.0%). Although most organisms were cultured in 5 days or less, 10.8 days were needed for Propionibacterium acnes, 6.6 for variant PJI organisms, and 5.2 for coagulase-negative Staphylococcus. At 3 days, only 42.2% of cultures turned positive compared with 95.0% at 8 days. There was a significant decrease in time in gram-positive PJIs and an increase in culture-negative PJIs. CONCLUSION: The optimal number of cultures and growth duration depended on the type of organism. This study provides evidence that 5 samples should be obtained and held for at least 8 days given that the type of organisms is likely to be unknown at the time of surgery.

Multidrug-Resistant Organisms in the Setting of Periprosthetic Joint Infection-Diagnosis, Prevention, and Treatment.

BACKGROUND: Periprosthetic joint infection (PJI) is a rare yet challenging problem in total hip and knee arthroplasties. The management of PJI remains difficult primarily due to the evolution of resistance by the infecting organisms. METHODS: This review profiles acquired mechanisms of bacterial resistance and summarizes established and emerging techniques in PJI diagnosis, prevention, and treatment. RESULTS: New techniques in PJI diagnosis and prevention continue to be explored. Antibiotics combined with 1 or 2-stage revision are associated with the higher success rates and remain the mainstay of treatment. CONCLUSION: With higher prevalence of antibiotic-resistant organisms, novel antibiotic implant and wound care materials, improved methods for organism identification, and well-defined organism-specific treatment algorithms are needed to optimize outcomes of PJI.

Infection risk assessment in patients undergoing primary total knee arthroplasty.

PURPOSE: To determine the incidence and to identify potential risk factors for in-hospital and late infections, as well as for deep periprosthetic joint infection (PJI) following TKA. METHODS: We identified 17,959 patients treated with primary TKA between 2000 and 2009. We recorded patient demographics, comorbidities and in-hospital complications. The rates of in-hospital, late, and deep PJIs were determined. Different logistic regression models were built to identify risk factors for each of the above types of infection. RESULTS: The rates for in-hospital, post-discharge, and deep PJI were 0.65%, 0.41%, and 0.26%, respectively. Younger age, allogeneic blood transfusion, liver disease, and unilateral or staged bilateral TKA were risk factors for in-hospital infection. Renal and pulmonary disease, urinary tract infection, wound dehiscence, and prior in-hospital infection were risk factors for post-discharge infection. Male gender, history of in-hospital infection, prolonged length of stay, and pulmonary disease were identified as risk factors for deep PJI. CONCLUSION: Despite low infection rates after primary TKA, there are patients at higher risk that would benefit by addressing modifiable risk factors for both in-hospital or post-discharge infections, including deep PJIs.

Diagnostic accuracy of synovial fluid, blood markers, and microbiological testing in chronic knee prosthetic infections.

INTRODUCTION: This retrospective study was undertaken to define cut-off values for synovial fluid (SF) leukocyte count and neutrophil percentage for differentiating aseptic failure and periprosthetic joint infection (PJI) and to evaluate the diagnostic accuracy of blood inflammatory markers, and microbiological testing according to the criteria proposed by the International Consensus Meeting (ICM) of Philadelphia. METHODS: All patients who underwent revision total knee arthroplasty from January 2010 to July 2015 were included: we identified and classified 31 PJIs and 136 aseptic joints. The diagnostic performance of single test was assessed by receiver operating characteristic curve analyses. The sensitivity and specificity were calculated for each of the cut-off values and the area under the curve (AUC) was calculated. RESULTS: The median SF leukocyte count as well as the neutrophil percentage and inflammatory markers were significantly higher in patients with PJI than in those with aseptic failure (p < 0.001). A leukocyte count of > 2.8 × 103/µL had a sensitivity of 83.8% and a specificity of 89.7% whereas a neutrophil percentage of > 72% yielded a marginally higher sensitivity of 84% and a specificity of 91%. Applying the ICM criteria we found a significant correlation between all these diagnostic measures and PJI (p < 0.001) except for a single positive culture. The most accurate criterion of the ICM was the synovial neutrophil differential (AUC = 0.89; 95% CI 0.81-0.97), followed by SF leukocyte count (AUC = 0.86; 95% CI 0.78-0.94), increased inflammatory markers (AUC = 0.85; 95% CI 0.76-0.93), and two positive periprosthetic cultures (AUC = 0.84; 95% CI 0.73-0.94). The presence of sinus tract communicating with the joint and a single positive culture showed unfavourable diagnostic accuracy (AUC = 0.60, 95% CI 0.47-0.72; AUC = 0.49, 95% CI 0.38-0.61, respectively) CONCLUSIONS: The present study highlights the adequate ability of fluid cell count and neutrophil differential to distinguish between PJI and aseptic loosening. The clinical utility of fluid analysis in diagnosing infection can be improved by evaluation of other diagnostic criteria. LEVEL OF EVIDENCE: Level I Diagnostic Study.

[Immunohistochemical Detection of Mast and Dendritic Cells in Periprosthetic Tissues of Aseptically Loosened Total Prostheses]. / Imunohistochemický prukaz mastocytu a dendritických bunek v periprotetických tkáních asepticky uvolnených endoprotéz.

PURPOSE OF THE STUDY This study deals with the possibilities and application of immunohistochemical methods to detect mast and dendritic cells in periprosthetic tissues in patients with aseptically loosened total joint replacements of the knee and hip. The purpose of the study was to quantify and characterize the distribution of mast and dendritic cells in the examined samples and to study the statistically significant relations between the aforementioned cell populations and selected parameters characterizing the patients, implants or tissue response. Based on the proved findings, a possible relation between mast and dendritic cells and histomorphological patterns of aseptic loosening and the benefit of the applied immunohistochemical methods was evaluated. MATERIAL AND METHODS Periprosthetic tissues from a total of 31 patients (17 patients after a revision surgery of hip prosthesis, 14 patients after a revision surgery of knee prosthesis) were examined. The collected samples were processed according to the standard protocol for the purposes of histological and immunochemical examination. Antibodies against tryptase and CD117 were used for immunohistochemical detection of mast cells. Dendritic cells were detected by means of S100 and CD1a antibodies. Quantification of both the cell populations was carried out by optical microscopy in 20 high power fields at 400-times magnification. From among the applied methods we picked the more sensitive one for statistical evaluation. It was tryptase in the case of mast cells and S100 in the case of dendritic cells. RESULTS Mast and dendritic cells were mostly distributed dispersively in periprosthetic tissues; however, they also occurred in groups perivasally or near necrotic parts. The examined samples showed the presence of 60 mast cells and 50 dendritic cells on average. The increased density of mast and dendritic cells was associated with polypously formed pseudosynovium and cement fixation of prostheses; this relation was statistically significant. It was impossible to prove the correlation between the quantity of the observed cell populations and the nature and the number of the observed particles because wear particles were present dispersely in all the samples. Another statistically significant relation to the type of material or implant fixation or other examined histomorphological patterns was not proved. A strong density of mast cells with a minimum presence of dendritic cells was observed in the control patient group. DISCUSSION The differences in density of S100 positive dendritic cells between the control and examined group of patients can be caused by the activation of dendritic cells by exogenous or endogenous pathways of immune processes going on after the implantation of endoprosthesis. The statistically significant interrelation of mast cells, polypously formed pseudosynovium and cement wear particles can be explained at least in part as a tissue reaction induced by cement particles. CONCLUSIONS We proved the presence of two immunologically significant cell populations in periprosthetic tissues. The said findings indicate a conclusion of significant functional participation of mast and dendritic cells in pathogenesis of aseptic loosening and periprosthetic osteolysis. Nevertheless, this will have to be proved in another way and with the use of another method. Key words:dendritic cells, mast cells, aseptic loosening, total joint replacement, immune reaction, adverse reaction.