Introduction. Despite recent advances in the diagnosis of periprosthetic joint infection(PJI), identifying the infecting organism continues to be a challenge, with up to a third of PJIs reported to have negative cultures. Current molecular techniques have thus far been unable to replace culture as the gold standard for isolation of the infecting pathogen. Next- generation sequencing(NGS) is a well-established technique for comprehensively sequencing the entire pathogen DNA in a given sample and has recently gained much attention in many fields of medicine. Our aim was to evaluate the ability of NGS in identifying the causative organism(s) in patients with PJI. Methods. After obtaining Institutional Review Board approval and informed consent for all study participants, samples were prospectively collected from 148 revision total joint arthroplasty procedures (83 knees, 65 hips). Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to the laboratory for NGS analysis (MicroGenDx). Deep tissue specimens were also sent to the institutional laboratory(Thomas Jefferson University Hospital) for culture. PJI was diagnosed using the Musculoskeletal Infection Society(MSIS) definition of PJI. Statistical analysis was performed using SPSS software. Results. Fifty-five revisions were considered infected; culture was positive in 40 of these (40/55, 72.7%), while NGS was positive in 47 (47/55, 85.5%). Among the positive cultures, complete concordance between NGS and culture was observed in 33 cases (33/40, 82.5%). One case was partially discordant between NGS and culture, with culture detecting three organisms as opposed to one organism on NGS. One case showed complete discordance with NGS and culture detecting different organisms. Three patients with negative NGS results had positive cultures. In another two cases culture simply reported the gross morphology of the organism but the phenotype was not identified, while NGS was able to definitively identify an organism. Among the 15 cases of culture-negative PJI, NGS was able to identify an organism in 10 cases (10/15, 66.7%). These data are summarized in Figure 1. Ninety-three revisions were considered to be aseptic; NGS exclusively identified microbes in 15 of 93 “aseptic” revisions (16.1%) and culture exclusively isolated an organism in 4 of 93 cases(5.3%). One case was positive on both NGS and culture, however the results were discordant from each other. The remaining cases (73/93, 78.5%) were both NGS and culture negative. NGS detected several organisms in most positive samples, with a greater number of organisms detected in aseptic compared to septic cases (6.8 vs. 4.0, respectively). Discussion. NGS was able to detect a pathogen in two-thirds of culture-negative cases and demonstrated a high rate of concordance with culture in culture-positive cases. The rate of false positives was low compared to earlier studies using molecular techniques. Our findings also suggest that some cases of PJI may be polymicrobial and escape detection using conventional culture. NGS may be a useful adjunct for identifying the causative organism(s) in PJI, particularly in the setting of negative cultures. Further study is required to determine the significance of isolated organisms in samples from patients who are not thought to be infected

Aim. The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepim as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies. Method. All patients with PJI empirically treated by vancomycin-cefepim (n=90) were prospectively enrolled in an observational study, and compared with vancomycin-piperacillin/tazobactam-treated historical controls (n=117), regarding: i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE). Results. Among the 146 (67.3%) documented infections, the EAT was considered as efficacious in 99 (99.0%) and 66 (98.5%) in the piperacillin-tazobactam and cefepim-treated patients, respectively (p=0.109). The rate of adverse events, and in particular AKI, was significantly higher in the vancomycin-piperacillin/tazobactam (n=38 [32.5%] and 32 [27.6%]) compared to the vancomycin-cefepim (n=13 [14.4%] and 5 [5.7%]) group (p=0.003 and <0.001, respectively). Of note, sex, age, and the proportion of patients receiving other nephrotoxics were similar among piperacillin/tazobactam- and cefepim-treated patients. However, in comparison with patients receiving cefepim, a higher modified Charlson's comorbitidy index (4 [IQR, 3–5] versus 2 [IQR, 2–4], p<0.001) has to be acknowledged, mainly related to a higher prevalence of baseline chronic renal injury (n=62, 53.4% versus n=34, 38.6%; p=0.035). Conclusions. The empirical use of vancomycin-cefepim in PJI was as efficient as vancomycin-piperacillin/tazobactam, and was associated with a significantly lower incidence of AKI

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. For most patients, antibiotics alone are not an acceptable method of treatment, and surgery is necessary. The standard of care for established infection is two stage revision with antibiotic loaded cement during the interval period and parental antibiotic therapy for six weeks. Single stage revision may have economic and functional advantages, however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Our protocol has included single stage revision using antibiotic loaded cement in both THA and TKA. This was only undertaken when sensitive organisms were identified pre-operatively by aspiration and appropriate antibiotics were available to use in cement. Patients with immunocompromise, multiple infecting organisms or recurrent infection were excluded. Patients with extensive bone loss that required allograft reconstruction or where a cementless femoral component was necessary were also excluded. Our algorithm was validated first in the hip and extended to infected TKA in 2004. This protocol has now been applied in over 100 TKA revisions for infection between 2004 and 2009. Our single stage revision rate is now over 25%. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two stage revision cases. Whilst our indications are arbitrary and not based on specific biomarkers, we present excellent results for selective single stage exchange. A minimum three year follow-up suggests that these patients have shorter hospital stays, higher satisfaction rates and better knee scores. An ongoing evaluation is in place. One stage revision arthroplasty for infection offers potential clinical and economic advantages in selected patients

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. Although there have been multiple developments to enhance our ability to effect two-stage techniques whilst limiting inpatient stay, cost and patient morbidity - these include functional spacers, the use of local as well as systemic antibiotics, and home intravenous therapy programmes – there is nevertheless still a considerable morbidity and mortality to the two-stage process, and a massive cost to the patient who has to have two operations with an unpredictable interval period in between and to the local tissues which have already been damaged and are violated on two occasions. The push for one-stage surgery has generally been from centers who are passionate about that technique and has involved a combination of knowing the organism in question prior to surgery, a very radical debridement, the use of hinge / tumor-type implants and prolonged antibiotic therapy post-surgery. The last decade has seen an evolution whereby we have recognised that treatment may be tailored to the patient. There is a big difference between a relatively healthy host and someone with multiple comorbidities, and a big difference between infection with a relatively benign organism and polymicrobial infection with multi-resistant bacteria or fungi. There has, therefore, been increased interest in the use of single-stage revision in order to decrease morbidity, potentially decrease mortality and to decrease cost to the health care system. Single stage revision may have economic and functional advantages, however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Whilst we believe that there is a role for both single- and two-stage techniques in our armamentarium, we have gradually evolved to increasing use of single-stage surgery. We use antibiotic-loaded cement whenever possible but can reconstruct most cases using semiconstrained implants without resorting to a hinge. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two-stage revision cases. We use hinge reconstruction in less than 20% of cases

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. For most patients, antibiotics alone are not an acceptable method of treatment, and surgery is necessary. The standard of care for established infection is two-stage revision with antibiotic loaded cement during the interval period and parental antibiotic therapy for six weeks. Single stage revision may have economic and functional advantages however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Our protocol has included single stage revision using antibiotic loaded cement in both THA and TKA. This was only undertaken when sensitive organisms were identified pre-operatively by aspiration and appropriate antibiotics were available to use in cement. Patients with immunocompromise, multiple infecting organisms or recurrent infection were excluded. Patients with extensive bone loss that required allograft reconstruction or where a cementless femoral component was necessary were also excluded. Our algorithm was validated first in the hip and extended to infected TKA in 2004. This protocol has now been applied in over 100 TKA revisions for infection between 2004 and 2009. Our single stage revision rate is now over 25%. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two-stage revision cases. Whilst our indications are arbitrary and not based on specific biomarkers, we present excellent results for selective single stage exchange. A minimum three-year follow-up suggests that these patients have shorter hospital stays, higher satisfaction rates and better knee scores. An ongoing evaluation is in place. One-stage revision arthroplasty for infection offers potential clinical and economic advantages in selected patients

Aim. To describe the epidemiology, clinical features and outcomes of native joint septic arthritis in adults admitted to Middlemore Hospital in Auckland, New Zealand. Method. Single-centre retrospective cohort study from 2009 to 2014. Patients ≥16 years of age were identified using ICD-10AM coding data. Electronic records were reviewed for demographic, clinical, laboratory, treatment and outcome data. Total and hemi-arthroplasty infections were excluded. Results. 543 episodes in 521 patients were included, with 90% fulfilling Modified Newman's criteria. Septic arthritis incidence was 26/100,000 patient years and was unchanged over the study period. Incidence correlated strongly with age (R. 2. =0.79) and socioeconomic deprivation (R. 2. =0.76). Median age was 49 years, and gender 70% male. Ethnicity was Pacific Island in 36% (22.8% of catchment population). The most commonly involved joints were hand interphalangeal (19%), knee (19%), metacarpophalangeal (17%) and glenohumeral (11%). Arthritis was monoarticular in 93%. Underlying conditions included current smoking (42%), osteoarthritis (29%), diabetes (22%) and gout (15%). Rheumatoid and seronegative arthritis were uncommon (each 2%). Skin/soft tissue infection occurred within 3 months prior in 38%. Osteomyelitis occurred in 26%. Sources of infection included haematogenous (42%), traumatic (34%), and iatrogenic (17%). Causative organism(s) were isolated in 80% of episodes, most commonly Staphylococcus aureus (53%, 13% of which were MRSA) then Streptococcus pyogenes (15%). 28% of culture-positive episodes were polymicrobial. Median antibiotic duration was 4 weeks, with 38% having definitive therapy orally. A median of 1 surgical procedure was undertaken during treatment. Mortality at 30 days was 3%, at 90 days 5% and treatment failure (defined as any of: death <90 days; relapse; reinfection; or ongoing joint infection leading to readmission, amputation, arthrodesis or excision arthroplasty) occurred in 17%. Treatment failure was significantly more common in cases involving large joints (23%, (69/302) vs. 11%, (26/241), p=0.0002) and in haematogenous episodes versus traumatic episodes (21% (47/229) vs. 10% (19/168), p=0.0045). Conclusions. This is the largest series of adult native joint septic arthritis currently available. The extremely high observed septic arthritis incidence (26/100,000 person years) may relate to high rates of skin and soft tissue infection in Auckland, particularly among Pacific people. Small joint infection, often excluded from previous studies, is associated with significantly better outcomes than large-joint infection. Mortality is lower in this cohort than previously reported, possibly due to the inclusion of small joint infections and exclusion of prosthetic joint infections. Acknowledgements. No additional funding was received for this work

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. For most patients, antibiotics alone are not an acceptable method of treatment, and surgery is necessary. The standard of care for established infection is two-stage revision with antibiotic-loaded cement during the interval period and parental antibiotic therapy for six weeks. Single-stage revision may have economic and functional advantages however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Our protocol has included single-stage revision using antibiotic-loaded cement in both THA and TKA. This was only undertaken when sensitive organisms were identified pre-operatively by aspiration and appropriate antibiotics were available to use in cement. Patients with immunocompromise, multiple infecting organisms or recurrent infection were excluded. Patients with extensive bone loss that required allograft reconstruction or where a cementless femoral component was necessary were also excluded. Our algorithm was validated first in the hip and extended to infected TKA in 2004. This protocol has now been applied in over 100 TKA revisions for infection between 2004 and 2009. Our single-stage revision rate is now over 25%. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two-stage revision cases. Whilst our indications are arbitrary and not based on specific biomarkers, we present excellent results for selective single-stage exchange. A minimum three-year follow up suggests that these patients have shorter hospital stays, higher satisfaction rates and better knee scores. An ongoing evaluation is in place. One-stage revision arthroplasty for infection offers potential clinical and economic advantages in selected patients

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a sub optimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. For most patients, antibiotics alone are not an acceptable method of treatment, and surgery is necessary. The standard of care for established infection is two stage revision with antibiotic loaded cement during the interval period and parental antibiotic therapy for six weeks. Single stage revision may have economic and functional advantages however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Our protocol has included single stage revision using antibiotic loaded cement in both THA and TKA. This was only undertaken when sensitive organisms were identified preoperatively by aspiration and appropriate antibiotics were available to use in cement. Patients with immunocompromise, multiple infecting organisms or recurrent infection were excluded. Patients with extensive bone loss that required allograft reconstruction or where a cementless femoral component was necessary were also excluded. Our algorithm was validated first in the knee and extended to infected TKA in 2004. This protocol has now been applied in over 100 TKA revisions for infection between 2004 and 2009. Our single stage revision rate is now over 25%. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two stage revision cases. Whilst our indications are arbitrary and not based on specific biomarkers, we present excellent results for selective single stage exchange. A minimum three year follow-up suggests that these patients have shorter hospital stays, higher satisfaction rates and better knee scores. An ongoing evaluation is in place. One stage revision arthroplasty for infection offers potential clinical and economic advantages in selected patients

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; sd 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6.