Periprosthetic knee infection reconstruction with a hinged prosthesis: Implant survival and risk factors for treatment failure

BackgroundSevere bone and soft tissue defects are common after failed two-stage exchange arthroplasty for periprosthetic joint infection (PJI). There is a paucity of evidence on the outcomes of using a hinged prosthesis for knee PJI reconstruction during second-stage re-implantation, especially regarding implant survivorship, reinfection risk factors, and functionality after successful reconstruction.MethodsA total of 58 knee PJI patients with Anderson Orthopaedic Research Institute (AORI) type II/III defect and soft tissue insufficiency underwent reconstruction with hinged prosthesis. Enrolled patients adhered to a two-stage exchange arthroplasty protocol and were evaluated for a mean follow up of 65.1 months. Kaplan–Meier analysis was conducted for implant survivorship and infection-free survival. Multivariate analysis was used to determine independent risk factors for recurrent infections. Knee Society Score (KSS) was used to evaluate functional outcomes.ResultsThe survivorship of hinged prosthesis was 86.2% at 2 years and 70.2% at 5 years. Infection-free analysis revealed an estimation of 68.9% at 2 years and 60.6% at 5 years. Of the 58 patients, 13 (22.4%) developed recurrent PJI, three (5.2%) aseptic loosening, and one (1.7%) periprosthetic fracture. Multivariate analysis revealed that obesity (hazard ratio (HR), 3.11), high-virulent pathogen (HR, 3.44), and polymicrobial infection (HR, 3.59) were independent risk factors for reinfection. Patients showed a mean improvement of 32.8 ± 7.7 in Knee Society Clinical Score (KSCS) and 30.8 ± 11.0 in Knee Society Function Score (KSFS) after successful reconstruction (P < 0.001).ConclusionsUsing hinged knee prosthesis for PJI reconstruction provided an overall implant survival of 70.2% and an infection-free survival of 60.6% at mid-term follow up. Obesity, virulent pathogens, and polymicrobial infections were independent risk factors for infection recurrence.     

Microbiology of hip and knee periprosthetic joint infections: a database study

ObjectivesKnowledge of the microbiological aetiology of periprosthetic joint infection (PJI) is essential to its management. Contemporary literature from the United States on this topic is lacking. This study aimed to identify the most common microorganisms associated with types of arthroplasty, the timing of infection, and clues to polymicrobial infection.MethodsWe performed an analytical cross-sectional study of patients 18 years of age or older with hip or knee PJI diagnosed at our institution between 2010 and 2019. PJI was defined using the criteria adapted from those of the Musculoskeletal Infection Society. Cases included PJI associated with primary or revision arthroplasty and arthroplasty performed at our institution or elsewhere.ResultsA total of 2067 episodes of PJI in 1651 patients were included. Monomicrobial infections represented 70% of episodes (n = 1448), with 25% being polymicrobial (n = 508) and the rest (5%, n = 111) culture-negative. The most common group causing PJI was coagulase-negative Staphylococcus species (other than S. ludgunensis) (37%, n = 761). The distribution of most common organisms was similar regardless of arthroplasty type. The S. aureus complex, Gram-negative bacteria, and anaerobic bacteria (other than Cutibacterium species) were more likely to be isolated than other organisms in the first year following index arthroplasty (OR 1.7, 95%CI 1.4–2.2; OR 1.5, 95%CI 1.1–2.0; and OR 1.5, 95%CI 1.0–2.2, respectively). The proportion of culture-negative PJIs was higher in primary than revision arthroplasty (6.5% versus 3%, p 0.0005). The presence of a sinus tract increased the probability of the isolation of more than one microorganism by almost three-fold (OR 2.6, 95%CI 2.0–3.3).ConclusionsJoint age, presence of a sinus tract, and revision arthroplasties influenced PJI microbiology.     

Rifampicin–fosfomycin coating for cementless endoprostheses: Antimicrobial effects against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA)

New strategies to decrease infection rates in cementless arthroplasty are needed, especially in the context of the growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections. The purpose of this study was to investigate the antimicrobial activity of a rifampicin–fosfomycin coating against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA in a rabbit infection prophylaxis model. Uncoated or rifampicin–fosfomycin-coated K-wires were inserted into the intramedullary canal of the tibia in rabbits and contaminated with an inoculation dose of 10⁵ or 10⁶ colony-forming units of MSSA EDCC 5055 in study 1 and MRSA T6625930 in study 2, respectively. After 28 days the animals were killed and clinical, histological and microbiological assessment, including pulse-field gel electrophoresis, was conducted. Positive culture growth in agar plate testing and/or clinical signs and/or histological signs were defined positive for infection. Statistical evaluation was performed using Fisher’s exact test. Both studies showed a statistically significant reduction of infection rates for rifampicin–fosfomycin-coated implants compared to uncoated K-wires (P = 0.015). In both studies none of the 12 animals that were treated with a rifampicin–fosfomycin-coated implant showed clinical signs of infection or a positive agar plate testing result. In both studies, one animal of the coating group showed the presence of sporadic bacteria with concomitant inflammatory signs in histology. The control groups in both studies exhibited an infection rate of 100% with clear clinical signs of infection and positive culture growth in all animals. In summary, the rifampicin–fosfomycin-coating showed excellent antimicrobial activity against both MSSA and MRSA, and therefore warrants further clinical testing.     

The impact of preoperative bacteriuria on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow up

ObjectivesPatients who undergo elective joint replacement are traditionally screened and treated for preoperative bacteriuria to prevent periprosthetic joint infection (PJI). More recently, this practice has been questioned. The purpose of this study was to determine whether preoperative bacteriuria is associated with an increased risk of PJI.MethodsPatients who had undergone a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified from the hospital database (23 171 joint replacements, 10 200 hips, and 12 971 knees). The results of urine cultures taken within 90 days before the operation were obtained. Patients with subsequent PJI or superficial wound infection in a 1-year follow-up period were identified based on prospective infection surveillance. The association between bacteriuria and PJI was examined using a multivariable logistic regression model that included information on the operated joint, age, gender and the patients' chronic diseases.ResultsThe incidence of PJI was 0.68% (n = 158). Preoperative bacteriuria was not associated with an increased risk of PJI either in the univariate (0.51% versus 0.71%, OR 0.72, 95% CI 0.34–1.54) or in the multivariable (OR 0.82, 95% CI 0.38–1.77) analysis. There were no cases where PJI was caused by a pathogen identified in the preoperative urine culture. Results were similar for superficial infections.ConclusionsThere was no association between preoperative bacteriuria and postoperative surgical site infection. Based on these results, it seems that the preoperative screening and treatment of asymptomatic bacteriuria is not required.     

Challenges in periprosthetic knee-joint infection

The number of knee arthroplasty procedures is growing and projected to further increase. The risk for periprosthetic joint infection (PJI) is estimated to be low (<1%). However, considering the increasing number of total knee arthroplasty, the increasing number of patients with multiple comorbidities, and the lifelong risk for acquiring hematogenous infection, the total number of PJI will further increase. Despite existing treatment concepts for PJI of the knee, there are still questions to solve, such as type of debridement surgery in case of implant retention, the role of a spacer from a microbiological perspective, and the optimal duration of antimicrobial therapy. In this REVIEW, these questions will be analyzed according to the available literature and the experience of the authors. Moreover, we REVIEW the most recent data on infection, risk factors, and microbiology of PJI.     

Prosthetic joint infection of the knee - arthroscopic biopsy identifies more and different organisms than aspiration alone

BackgroundProsthetic joint infection (PJI) causes significant morbidity and mortality following knee replacement surgery. Identifying causative organisms and antibiotic sensitivities is critical in increasing the chance of infection eradication. This study investigated whether biopsy alone was superior to aspiration alone for serological diagnosis in PJI following knee replacement. Secondly, we investigated whether biopsy identifies the same or new/different microbiological flora as aspiration.MethodsSince December 2014, the Exeter Knee Reconstruction Unit (EKRU) has prospectively collated data regarding all PJIs referred from our local/regional network which have been reviewed via our Multi-Disciplinary Team (MDT). We identified and included consecutive patients from this MDT from Dec.2014-Mar.2020 and analysed their electronic records. Statistical analysis was performed using Stata.Results65/100 patients studied had both pre-operative aspiration and biopsy. 31/65 (48%) had positive aspiration and biopsies. No aspirate samples were positive with corresponding biopsies negative. In 19/65 (29%) of infection positive patients, biopsy identified new (7) or additional (12) organisms not identified by aspiration. Aspiration had a sensitivity of 70%, specificity of 88%, positive predictive value of 90.3% and negative predictive value of 64.7%. Biopsy had a sensitivity of 97.5%, specificity of 88%, positive predictive value of 92.9% and negative predictive value of 95.7%.ConclusionIn 29% of confirmed PJI cases, arthroscopic biopsy identified either additional organisms in a polymicrobial PJI when compared to aspiration, or new positive results when aspiration alone was negative. This study demonstrates the benefits of arthroscopic biopsy for serological diagnosis in cases of knee PJI and aids treatment planning.     

The effect of preoperative oral antibiotic use on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow-up

ObjectivesAntibiotics are used for various reasons before elective joint replacement surgery. The aim of this study was to investigate patients' use of oral antibiotics before joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI).MethodsPatients having a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified (n = 23 171). Information on oral antibiotic courses purchased 90 days preoperatively and patients' chronic diseases was gathered. Patients with a PJI in a 1-year follow-up period were identified. The association between antibiotic use and PJI was examined using a multivariable logistic regression model and propensity score matching.ResultsOne hundred and fifty-eight (0.68%) cases of PJI were identified. In total, 4106 (18%) joint replacement operations were preceded by at least one course of antibiotics. The incidence of PJI for patients with preoperative use of oral antibiotics was 0.29% (12/4106), whereas for patients without antibiotic use it was 0.77% (146/19 065). A preoperative antibiotic course was associated with a reduced risk for subsequent PJI in the multivariable model (OR 0.40, 95% CI 0.22–0.73). Similar results were found in the propensity score matched material (OR 0.34, 95% CI 0.18–0.65).ConclusionsThe use of oral antibiotics before elective joint replacement surgery is common and has a potential effect on the subsequent risk for PJI. Nevertheless, indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though treatment of active infections remains an important way to prevent surgical site infections.     

Rapid Molecular Microbiologic Diagnosis of Prosthetic Joint Infection

We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.     

Origin and characteristics of haematogenous periprosthetic joint infection

ObjectivesRecognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI.MethodsConsecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and Mann–Whitney U tests were used, as appropriate.ResultsA total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1–417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n = 43), streptococci (n = 32), enterococci (n = 13), Gram-negative bacteria (n = 9) and coagulase-negative staphylococci (n = 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes).ConclusionsIn acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.     

Unicompartmental knee arthroplasty is associated with lower proportions of surgical site infection compared with total knee arthroplasty: A retrospective nationwide database study

BackgroundThis study aimed to clarify the association between types of knee arthroplasty (KA) (total knee arthroplasty (TKA) or unicompatmental knee arthroplasty (UKA)) and surgical site infection (SSI) with adjustment for various factors, using a Japanese national database.MethodsData on 181,608 patients who underwent unilateral primary KA for osteoarthritis from 2010 to 2017 were obtained from the Japanese Diagnosis Procedure Combination database. SSI was identified based on International Classification of Diseases 10th Revision codes. Deep SSI (i.e. periprosthetic joint infection (PJI)) was identified as SSI treated with surgical procedures. Multivariable logistic regression analyses for SSI and PJI were performed, in which dependent variables included types of KA, patient backgrounds (sex, age, body mass index (BMI), smoking status, comorbidities), and seasonality.ResultsEight percent of analyzed patients underwent UKA, while 92% underwent TKA. The proportions of SSI and PJI after UKA were 0.9% and 0.3%, respectively, both of which were lower than those after TKA (1.9% and 0.6%) (P < 0.001). Multivariable analyses showed lower proportions of SSI for UKA (adjusted odds ratio, 0.47; 95% confidence interval, 0.37–0.60; P < 0.001) and PJI (adjusted odds ratio, 0.47; 95% confidence interval, 0.34–0.65; P < 0.001) than TKA. Other factors associated with both SSI and PJI included male sex, BMI >30 kg/m², renal dysfunction and summer season.ConclusionUKA was associated with lower proportions of SSI and PJI than TKA. Surgeons should carefully consider the indication of UKA before performing TKA, especially in patients with knee unicompartmental osteoarthritis who are at a high risk for SSI or PJI.     

Avoidance of intramedullary violation in computer-assisted total knee arthroplasty lowers the incidence of periprosthetic joint infection compared with conventional total knee arthroplasty: A propensity score matching analysis of 5342 cases

BackgroundConventional total knee arthroplasty (CONV-TKA) inevitably perturbs femoral medullary canal, disturbs medullary micro-architecture and increases blood loss and inflammatory responses. We hypothesized that avoidance of intramedullary violation may lower the incidence of periprosthetic joint infection (PJI). The aim of this study was to verify whether computer-assisted total knee arthroplasty (CAS-TKA) lowers the incidence of PJI as compared with CONV-TKA.MethodsA propensity score matching study of 5342 patients who underwent CAS-TKA (n = 1085) or CONV-TKA (n = 4257) for primary osteoarthritis of the knee from 2007 to 2015 in our institute was performed. Patients who underwent CAS-TKA were matched to those who received CONV-TKA at a 1:2 ratio according to demographics and comorbidities. PJI was defined according to the Musculoskeletal Infection Society diagnostic criteria from the 2013 International Consensus Meeting.ResultsAfter controlling potential risk factors, the use of CAS-TKA resulted in a lower incidence of PJI as compared with CONV-TKA [adjusted hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.18–0.99]. The same trend in PJI reduction was observed with the usage of CAS-TKA under sensitivity testing [HR, 0.33; 95% CI, 0.12–0.95]. The cumulative incidence of PJI was lower in the CAS-TKA group than the CONV-TKA group (log-rank test, p = 0.013).ConclusionAvoidance of intramedullary violation during TKA may play a pivotal role in lowering the incidence of PJI. The use of CAS-TKA can reduce the incidence of PJI, with a better survival rate in terms of being free of PJI, as compared with CONV-TKA.Level of evidence III.     

Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection

We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% (P ≤ 0.001), respectively, and specificities were 91.8% and 97.4% (P = 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively (P < 0.0001). In this group, the PCR panel detected Staphylococcus aureus in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid.     

Investigation and management of prosthetic joint infection in knee replacement: A BASK Surgical Practice Guideline

BackgroundThe burden of knee replacement prosthetic joint infection (KR PJI) is increasing.KR PJI is difficult to treat, outcomes can be poor and it is financially expensive and limited evidence is available to guide treatment decisions.AimTo provide guidelines for surgeons and units treating KR PJI.MethodsGuideline formation by consensus process undertaken by BASK's Revision Knee Working Group, supported by outputs from UK-PJI meetings.ResultsImproved outcomes should be achieved through provision of care by revision centres in a network model. Treatment of KR PJI should only be undertaken at specialist units with the required infrastructure and a regular infection MDT.This document outlines practice guidelines for units providing a KR PJI service and sets out:

• •The necessary infrastructure required to provide a high-quality KR PJI service
• •The MDT composition — who and when
• •The KR PJI care pathway
• •Medical and surgical treatment strategies
• •The indications for referral to tertiary units (Major Revision Centres)
• •Outcome metrics and auditable standards

ConclusionsKR PJI patients treated within the NHS should be provided the best care possible. This report sets out guidance and support for surgeons and units to achieve this.     

Microbiological Profile and Outcomes of Two-Stage Revision Hip Arthroplasty

Background: Prosthetic joint infection (PJI) is one of the most challenging cases that confront modern orthopaedics. Two-stage revision, which is the standard of care for PJI, is the preferred mode of treatment for these infections. Aims and Objectives: To study the microbiological profile of prosthetic joint infections (PJI) in the hip and to assess the efficacy of a two stage revision surgery for PJI. We also aimed to study the sensitivity and specificity of ESR and CRP in the diagnosis of PJI. Materials and Methods: The microbiological profile, clinical and radiological outcomes of 22 patients who had a two-stage revision for PJI of the hip between 2013 and 2017 were retrospectively analysed. PJI was defined using the criteria provided by the International Consensus Statement on PJI 2013. Results: Staphylococcus aureus was found to be the most common organism in PJI. Debridement was successful in removing the organism in 74% of PJI. At the time of re-implantation (second stage), six joints grew organisms that were different from that isolated at the index debridement - coagulase-negative staphylococci (3cases) and enterococci (3cases). Other infection parameters for these patients were negative. None of the patients who had two-stage revision surgery had clinical evidence of reinfection or radiological evidence of loosening at a mean of 2-year follow-up. An ESR cut off of >30mm/hr had a sensitivity of 75% and specificity of 88% in predicting PJI. A CRP >10mg/L had a sensitivity of 75% and specificity of 69%. The sensitivity and specificity of using both ESR and CRP cut-offs in the diagnosis of infection were 57% and 94%, respectively. The positive predictive value was 94% and negative predictive value was 56%. Conclusion: The outcomes of the study justify a two-stage revision arthroplasty for PJI of the hip. The use of ESR and CRP as screening tests for the success of debridement has value - but should be interpreted with caution.     

Current and Future Burden of Periprosthetic Joint Infection from National Claim Database

BackgroundPeriprosthetic joint infection (PJI) is the most serious complication after total joint arthroplasty. The incidence and burden of PJI in North America have been reported. There might be potential differences according to ethnics and regional practices between western countries and East Asia. Nevertheless, its incidence in East Asia remains unknown. We aimed to evaluate the incidence and economic burden of PJI in Korea and to project the future burden.MethodsWe identified numbers of total hip arthroplasties, total knee arthroplasties and PJIs in Korea from 2010 to 2018 using medical claim data of Korean Health Insurance and Review and Assessment. Annual incidence and medical cost of PJI were calculated. We projected future burden of PJI through 2030 using Quasi-poisson regression model.ResultsThe annual incidence of PJI ranged from 2.3% to 2.8% and the average cost per each PJI patient ranged from $4,361 to $6,016. Total annual cost of PJI increased from $8.0 million in 2010 to $18.0 million in 2018 and was projected to exceed $57.0 million by 2030.ConclusionThe incidence of PJI in Korea is comparable with reported PJI incidence of 2.0%–2.7% in the United States. Our findings would be used for worldwide comparison of PJI epidemiology and establishment of healthcare policies for PJI in East Asia.     

Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy

Recent expert reviews recommend a conservative surgical strategy – debridement and irrigation, antibiotics and implant retention (DAIR) – for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable was associated with treatment failure following multivariate analysis. Seventy-four per cent of patients who were successfully treated by DAIR and only 32.7% of the failures were able to walk without help or with one stick at the last follow-up visit (p <0.05). In conclusion, a substantial proportion of patients with an early PJI may be successfully treated with DAIR and definite antimicrobial therapy. In more than half of these, the infection can be cured. Since identification of factors associated with failure of DAIR is not simple, we recommend offering DAIR to most patients with early PJI.     

Effects of intra-articular D-amino acids combined with systemic vancomycin on an experimental Staphylococcus aureus-induced periprosthetic joint infection

BackgroundThe D-isoforms of amino acids (D-AAs) exhibit anti-biofilm potential against a diverse range of bacterial species in vitro, while its role in vivo remains unclear. The aim of this study was to investigate the effects of a combination of D-AAs and vancomycin on a PJI rat model.MethodsEight-week-old male SD rats were randomized to the control group, sham group, vancomycin group, D-AAs–vancomycin group. After treatment for 6 weeks, we analysed the levels of inflammatory factors in serum, behavioural change, imaging manifestations. The anti-biofilm ability of D-AAs was detected by crystal violet staining and scanning electron microscope observation, and its ability to assist antibiotics in killing bacteria was assessed by culture of bacteria. Additionally, micro-CT and histological analysis were used to evaluate the impact of D-AAs combined with vancomycin on the bone remodelling around the prosthesis.ResultsThe group treated with a D-AAs–vancomycin combination sustained normal weight gain and exhibited reduced the serum levels of α2M, IL-1β, IL-6, IL-10, TNF-α and PGE2. Moreover, treated with D-AAs in combination with vancomycin improved the weight-bearing activity performance, increased the sizes and widths of distal femurs, and improved Rissing scale scoring. In particular, treatment using D-AAs enhanced the ability of vancomycin to eradicate Staphylococcus aureus, as demonstrated by the dispersion of existing biofilms and the inhibition of biofilm formation that occurred in a concentration-dependent manner. This treatment combination also resulted in a reduction in bacterial burden with in the soft tissues, bones, and implants. Furthermore, D-AAs–vancomycin combination treatment attenuated abnormal bone remodelling around the implant, as evidenced by an observed increase in BMD, BV/TV, and Tb.Th and the presence of reduced Trap⁺ osteoclasts and elevated osterix⁺ osteo-progenitors.ConclusionsCombining D-AAs with vancomycin provides an effective therapeutic strategy for the treatment of PJI by promoting biofilm dispersion to enhance antimicrobial activity.     

A case report demonstrating the utility of next generation sequencing in analyzing serial samples from the lung following an infection with influenza A (H7N9) virus

BackgroundBacterial pneumonia is a well-recognized sequela of patient suffering from influenza, and a key factor, with cytokine dysregulation, that contribute to severe disease and mortality.ObjectivesTo obtain a comprehensive assessment of lung microbial community dynamics in a fatal influenza H7N9 case during the whole clinical course, we undertook a longitudinal study.Study designSerial bronchoalveolar lavage fluid samples were collected from a H7N9 patient after illness onset, and the microbiome was characterized by using next-generation sequencing and microbiological approaches. Furthermore, the kinetics of circulating cytokine storms related to viral and secondary bacterial infection were analyzed.ResultsWithin complex and dynamic communities, the lung microbiome with H7N9 infection were dominated by gram-negative bacteria, Acinetobacter baumannii after the viral invasion and during the whole clinical course. Sputum and blood culture confirmed the secondary bacterial infection with multidrug-resistant A. baumannii 9 days later. The dynamics of the bacterial infection with carbapenem-resistant A. baumannii correlated with antibiotic therapy. Our observations also indicated that sustained high levels of host inflammatory factors, consisting of a set of distinct cytokines associated with disease stage, may contribute to disease progression and death.ConclusionsThis study demonstrates an initial attempt to explore the dynamic microbiome involved inH7N9 infection and its response to antimicrobial therapy, as well as host cytokine response to infection by using next-generation sequencing. These type of investigations with longitudinal follow-up to understand dynamics of microbial community and cytokines involved in lung infection may provide opportunities for development and optimization of targeted antimicrobial therapy and even new therapeutic strategies.     

Diagnosis of knee prosthetic joint infection; aspiration and biopsy

BackgroundProsthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. The diagnosis can be challenging and is based on a combination of clinical suspicion, radiographic findings and also biochemical/ microbiological investigations. Our Aim was to review the role of aspiration and biopsy in the diagnosis of PJI in Total Knee Arthroplasty (TKA).Method/resultsAspirated synovial fluid should be analysed by direct culture, via blood culture bottles, EDTA bottles for cell count and ‘point of care’ testing such as leucocyte esterase or alpha defensin. Synovial WCC and PMN cell percentage are important steps in diagnosis of both acute and chronic PJI. A minimum of 5 deep samples using a 5 clean instrument technique should be obtained and sent for tissue culture done either blind or arthroscopic. Formal fluoroscopic guided interface biopsy has also been described with excellent results. In a recent series of 86 TKRs preoperative arthroscopic biopsy group had a sensitivity of 100%, specificity of 94.7%, positive predictive value of 87.4% and a negative predictive value of 100%.ConclusionIn the presence of clinical suspicion with raised biomarkers, it is recommended that aspiration +/- biopsy with synovial fluid testing is performed. Direct culture and cell count are recommended. ‘Point of care tests’ such as Leucocyte Esterase testing should be considered. Duration of culture, including pathogen and host factors, should be discussed with a local microbiology/ID department in the context of a formal multi-disciplinary team.     

Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study

Objectives

The high microbiologic diversity encountered in prosthetic joint infection (PJI) makes the choice of empirical antimicrobial therapies challenging, especially in cases of implant retention or one-stage exchange. Despite the risk of dysbiosis and toxicity, the combination of vancomycin with a broad-spectrum β-lactam is currently recommended in all cases, even if Gram-negative bacilli (GNB) might be less represented in late PJI. In this context, this study aimed to describe the microbiologic epidemiology of PJI according to the chronology of infection.