Background: Prosthetic 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/results: Aspirated 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%. Conclusion: In 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 multidisciplinary team.

Background Total joint arthroplasty (TJA) is considered one of the most successful surgical procedures ever developed. It can successfully provide pain relief, restore joint function, and improve mobility and quality of life. Prosthetic joint infection (PJI) presents with a wide variety and severity of signs and symptoms. It remains a major threat to the outcome of TJA procedures and usually necessitates surgical intervention and prolonged courses of antibiotics. Inappropriate treatment of an unrecognized PJI usually ends with unacceptable and sometimes catastrophic results. The aim The understanding and evaluation of diagnostic investigations are extremely important to properly diagnose PJI, including frequently unrecognized low-grade infections, and to provide healthcare professionals with needed information for the care of patients affected by this condition. This article aims to review most of the methods available in PJI diagnostics, to emphasize the strengths and the weaknesses of each of them, and to provide a guideline on how to select the surgical treatment strategy based on the level of diagnostic certainty during the evaluation period. To safely accomplish this, it is crucial to be aware of the limitations of each diagnostic modality. The focus The emphasis will be on the use and interpretation of the core criteria for PJI diagnosis, including the pathognomonic sinus tract communicating with the implant, purulent synovial fluid, inflammation in the periprosthetic tissue, cell count with differential, microbial growth in the synovial fluid culture, tissue sample cultures, and sonication samples.

BACKGROUND: Ratios of established inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), have been used for diagnostic purposes in the surgical field; however, the ESR:CRP ratio (ECR) has not been evaluated as a marker for predicting infection resolution in patients with periprosthetic joint infections (PJIs). This study aimed to evaluate the diagnostic accuracy of ECR in predicting postoperative reinfection in patients who underwent debridement, antibiotics, and implant retention (DAIR). METHODS: This is a retrospective review of 179 consecutive patients who underwent DAIR revision total joint arthroplasty for PJI. Patients were stratified by acuity of their infection: acute PJI, acute hematogenous PJI, and chronic PJI. The area under the receiver operating characteristic curve was calculated to evaluate ECR as diagnostic marker for predicting postoperative reinfection in patients who underwent DAIR. RESULTS: Statistically significant differences in ECR were found in patients who underwent DAIR revision total joint arthroplasty for chronic infection (1.23 vs 2.33; P = .04). There was no significant difference in ECR in patients who underwent DAIR for acute infection (P = .70) and acute hematogenous infection (P = .56). In patients who underwent DAIR for chronic PJI, ECR demonstrated a sensitivity and specificity of 75% and 84%, respectively, for the prediction of postoperative reinfection, which was significantly higher than that of ESR (sensitivity, 67%; specificity, 47%; P < .001) and CRP (sensitivity, 50%; specificity, 26%; P < .001). CONCLUSION: Elevated ECR was associated with an increased reinfection risk in patients who underwent DAIR for chronic PJI, suggesting that preoperative ECR may be a useful predictor to identify patients at increased risk of reinfection after DAIR for chronic PJIs.

Periprosthetic joint infection (PJI) is a potentially devastating complication after total elbow arthroplasty (TEA) that can lead to significant morbidity for the patient as well as increased health care–related costs. Despite the potential morbidity associated with TEA PJI, evidence is limited regarding an optimal treatment algorithm. Initial management typically consists of either irrigation and debridement or 2-stage revision. A stable implant, a functioning triceps, and an intact soft tissue envelope are necessary to perform irrigation and debridement. Irrigation and debridement is associated with a relatively high risk of infection recurrence especially in chronic infections. Two-stage revision offers a lower recurrence risk, although there is a 25% chance of not completing the second stage. Resection arthroplasty, arthrodesis, and amputation are salvage options, whereas medical treatment, in the form of antibiotics alone, is reserved for poor surgical candidates. Further multicenter prospective study and retrospective review of registry data focusing on different treatment algorithms, prevention strategies, and functional outcomes would be helpful to elucidate the ideal management of elbow PJI.

Background The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. Methods We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up &lt;1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. Results We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1–2 was 42% (95/226), the rate for Week 3–4 was 38% (143/378), the rate for Week 5–6 was 29% (29/100), and the rate for Week 7–12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P &lt; .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. Conclusions DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.

Abstract. Background: Fungal prosthetic joint infections (PJIs) are rare and often associated with poor outcome; however, risk factors are not well described.Methods: This was a retrospective case control study among all patients with PJIs from 2006-2016 at two major academic centers. Each fungal PJI case was matched 1:1 with a bacterial PJI control by joint (hip, knee, shoulder) and year of diagnosis. We compared demographics, comorbidities, and clinical characteristics between cases and controls using chi square/Fisher's exact or Wilcoxon rank sum test. Independent risk factors were identified with multivariable logistic regression.Results: Forty-one fungal PJIs occurred over the study and 61% were due to Candida albicans. The hip was involved in 51.2% of cases, followed by the knee (46.3%). Compared to bacterial PJI, fungal PJI cases were more likely to have received antibiotics within the previous 3 months (70.7% vs 34%, P=.001), wound drainage lasting >5 days (48% vs 9%, P=.0002), had a lower median CRP (2.95 mg/dl vs 5.99, P=.013) and synovial fluid white blood cell count (13,953 cells/mm3 vs 33,198, P=.007), and a higher proportion of prior two-stage exchanges (82.9% vs 53.6%, P=.008). After controlling for center, prolonged wound drainage (OR, 7.3; 95% CI, 2.02-26.95) and recent antibiotics (OR, 3.4; 95% CI, 1.2-9.3) were significantly associated with fungal PJI.Conclusion: In our study, Candida albicans was the most common species in fungal PJIs and prolonged wound drainage and recent antibiotics were independent risk factors. These clinical characteristics may help providers anticipate fungal PJI and adjust management strategies.

Background Serum C-reactive protein (CRP) is an important test in the initial diagnosis of prosthetic joint infection (PJI). There is no widely accepted algorithm for the resolution of PJI. Surgeons have traditionally used CRP to determine if the infection has resolved. However, this practice is not currently supported by significant data.  Methods A retrospective analysis of our departmental arthroplasty database was conducted to determine mean values of CRP pre and postoperatively for PJI treated with the debridement, antibiotics and implant retention (DAIR) procedure, single-stage revision and two-stage revision. Receiver operating characteristic (ROC) curves were calculated to determine the sensitivity and specificity of CRP testing in diagnosing persistent infection. Results Of the 121 patients who had undergone treatment (75 hip replacements and 48 knee replacements), there were 26 cases of persistent infection. There was no statistical significance in the mean CRP values between successful and unsuccessful treatment groups. The areas under ROCs (AUCs) for CRP values predicting outcomes ranged from 0.46 to 0.73. Conclusion Our study does not support the use of serial CRP monitoring as an indicator of the successful eradication of PJI.

BACKGROUND: Total knee arthroplasty (TKA) periprosthetic joint infection (PJI) can be managed with debridement, antibiotic therapy, and implant retention (DAIR). Oral antibiotics can be used after DAIR for an extended time period to improve outcomes. The objective of this study was to compare DAIR failure rates and adverse events between an initial course of intravenous antibiotic therapy and the addition of extended treatment with oral antibiotics. METHODS: A multicenter observational study of patients diagnosed with a TKA PJI who underwent DAIR was performed. The primary outcome of interest was the failure rate derived from the survival time between the DAIR procedure and future treatment failure. RESULTS: One hundred eight patients met inclusion criteria; 47% (n = 51) received an extended course of oral antibiotics. These patients had a statistically significant lower failure rate compared to those who received only intravenous antibiotics (hazard ratio, 2.47; P = .009). Multivariable analysis demonstrated that extended antibiotics independently predicted treatment success, controlling for other variables. There was no significant difference in failure rates between an extended course of oral antibiotics less or more than 12 months (P = .23). No significant difference in the rates of adverse events was observed between patients who received an initial course of antibiotics alone and those who received a combination of initial and extended antibiotic therapy (P = .59). CONCLUSIONS: Extending therapy with oral antibiotics had superior infection-free survival for TKA PJI managed with DAIR. There was no increase in adverse events, demonstrating safety. After 1 year, there appears to be no significant benefit associated with continued antibiotic therapy.

Background We sought to determine the ultimate fate of patients undergoing resection arthroplasty as a first stage in the process of 2-stage exchange and evaluate risk factors for modes of failure. Methods A retrospective case study was performed including all patients with minimum 2-year follow-up who underwent first-stage resection of a hip or knee periprosthetic joint infection from 2008 to 2015. Patient demographics, laboratory, and health status variables were collected. The primary outcome analyzed was defined as failure to achieve an infection-free 2-stage revision. Univariate pairwise comparison followed by multivariate regression analysis was used to determine risk factors for failure outcomes. Results Eighty-nine patients underwent resection arthroplasty in a planned 2-stage exchange protocol (27 hips, 62 knees). Mean age was 64 years (range, 43-84), 56.2% were males, and mean follow-up was 56.3 months. Also, 68.5% (61/89) of patients underwent second-stage revision. Of the 61 patients who complete a 2-stage protocol, 14.8% (9/61) of patients failed with diagnosis of repeat or recurrent infection. Mortality rate was 23.6%. Multivariate analysis identified risk factors for failure to achieve an infection-free 2-stage revision as polymicrobial infection (P < .004; adjusted odds ratio [AOR], 7.8; 95% confidence interval [CI], 2.1-29.0), McPherson extremity grade 3 (P < .024; AOR, 4.1; 95% CI, 1.2-14.3), and history of prior resection (P < .013; AOR, 4.7; 95% CI, 1.4-16.4). Conclusion Patients undergoing resection arthroplasty for periprosthetic joint infection are at high risk of death (24%) and failure to complete the 2-stage protocol (32%). Those who complete the 2-stage protocol have a 15% rate of reinfection at 4.5-year follow-up.

Biofilm-active antibiotics are suggested to improve the outcome in periprosthetic joint infection (PJI). However, the type, dose and duration of antibiotic treatment is rarely specified and their impact on outcomes is unknown. In this prospective cohort study, the infection and functional outcome were compared in 131 patients with knee PJI treated with or without biofilm-active antibiotics. The infection and functional outcome were evaluated by the Kaplan–Meier survival method to estimate the probability of infection-free survival; comparison between subgroups was performed by log-rank test. The influence of variables on the survival probability was analysed using univariate and multivariate Cox proportional-hazards regression models. Functional outcome was evaluated by pain intensity and the Knee injury and Osteoarthritis Outcome Score (KOOS). Among the 131 patients, 55 (42%) were treated with biofilm-active antibiotics and 76 (58%) were treated with non-biofilm-active antibiotics. The median follow-up period was 3.7 years (range, 2.0–7.6 years), and the infection-free survival probability was 74% (95% CI 61–85%) after 1 year and 56% (95% CI 47–66%) after 2 years. Infection-free survival after 1 year was better for patients who received biofilm-active antibiotics compared with those who did not (83% vs. 70%; P = 0.040) and remained superior after 2 years (67% vs. 48%; P = 0.038). In addition, biofilm-active antibiotic treatment was associated with lower pain intensity (P = 0.006) and higher KOOS on all five subscales. In patients with knee PJI, biofilm-active antibiotic therapy was associated with better infection outcome, lower pain intensity and better joint function.

Background: A number of clinical trials have been conducted, assessing the role of long-term (>1 year) suppressive antibiotic treatment (SAT) combined with Debridement, Antibiotics, and Implant Retention (DAIR) for the management of peri-prosthetic joint infection (PJI). However, no systematic review of the literature has been published to date to evaluate complications associated with long-term antibiotic treatment and overall survivorship free from re-operation and revision for infection after DAIR for total hip and total knee PJI. Methods: The US National Library of Medicine (PubMed/MEDLINE), EMBASE, and the Cochrane Database of Systematic Reviews were queried for publications from January 1980 to December 2018 utilizing keywords pertinent to total knee arthroplasty, total hip arthroplasty, PJI, and antibiotic suppression. Results: Overall, 7 articles of low quality (level III or IV) were included in this analysis. The studies included in this systematic review included 437 cases of PJI treated surgically with DAIR and then with SAT. The overall mean infection-free rate of SAT following DAIR was 75% (318/424 patients), while the all-cause re-operation rate was 6.7%. Overall, the mean rate of adverse effects associated with long-term antibiotic use was 15.4% and the mean rate of adverse effects leading to discontinuation of SAT was 4.3%. There was no study to show significant differences between acute (either post-operative or hematogenous, with onset of symptoms ≤4 weeks) and chronic (onset of symptoms >4 weeks) infections and failure rates of DAIR with SAT. The literature is inconclusive on the influence of anatomic location (hip vs knee) as well as microorganism on the success rate of DAIR with SAT. Conclusion: The results of this systematic review demonstrate that there is still only low-quality evidence regarding the therapeutic effect of DAIR combined with SAT, which is not enough to draw definitive conclusions. Furthermore, high-quality prospective studies are needed to better understand SAT's efficacy and safety in a controlled fashion. Although discontinuation of antibiotic treatment due to side effects was found to be low, the high rates of adverse effects noted after DAIR with SAT demonstrate the underlying frailty and complexity of many patients with PJI, and the imperfect therapies available. Although Staphylococcus aureus appears to be a risk factor for increased risk of SAT failure, there are not enough data to establish which patients would benefit most from DAIR with post-operative SAT.

Aims The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9.

Introduction: Early recognition and appropriate initial treatment with debridement, antibiotics and implant retention (DAIR) if a suspicion of an early prosthetic joint infection (PJI) is present can eradicate infection on first attempt and prevent implant failure. We evaluated the outcome after 1 year of patients treated with DAIR after primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). Furthermore, we determined preoperative, microbiology, and treatment factors related to failure after DAIR. Methods: A retrospective cohort study was assembled with 91 patients undergoing DAIR with a high suspicion of an early PJI. Records were reviewed for demographics, preoperative laboratory results, microbiological data, given treatment and postoperative follow-up. The primary outcome was infection-free implant survival at 1 year. Repeated DAIR was not considered as treatment failure. Results: The rate of infection-free implant survival following DAIR in a suspected early PJI was 85% (95% confidence intervals (CI) 78-91). Cultures remained negative in 20 patients, with no occurrence of infection during follow-up. A higher failure rate was seen in early PJI caused by Enterococcus faecalis (p=0.04). Multivariate analysis showed a statistically significant association between treatment failure and high C-reactive protein level (CRP >100) (odds ratio 10.0, 95% CI [1.5-70]) and multiple DAIR procedures (≥2) (odds ratio 5.0, 95%CI [1.1-23]). Conclusion: If an early PJI is suspected DAIR is the appointed treatment with up to 2 debridement procedures. Since culture-negative DAIRs were not related to any complications during follow-up, overtreatment of suspected PJI seems to do no significant harm with respect to implant failure.

Background: For patients undergoing 2-stage exchange for the treatment of periprosthetic joint infection (PJI) following total knee arthroplasty, the long-term risk of reinfection and mechanical failure and long-term clinical outcomes are not well known. The purpose of our study was to determine the long-term clinical results of 2-stage exchange for PJI following total knee arthroplasty. Methods: We identified 245 knees that had undergone total knee arthroplasty and were subsequently treated with 2-stage exchange due to infection during the period of 1991 to 2006; the cohort had no prior treatment for PJI. Major, or 4 of 6 minor, Musculoskeletal Infection Society (MSIS) diagnostic criteria were fulfilled by 179 (73%) of the knees. The cumulative incidence of reinfection and of aseptic revision, accounting for the competing risk of death, were calculated. Risk factors for reinfection were evaluated using Cox proportional hazards regression. Knee Society Score (KSS) values were calculated. The mean age at spacer insertion was 68 years; 50% of the patients were female. The mean follow-up was 14 years (range, 2 to 25 years) following reimplantation. Results: The cumulative incidence of reinfection was 4% at 1 year, 14% at 5 years, 16% at 10 years, and 17% at 15 years. Factors that were predictive of reinfection included a body mass index of ≥30 kg/m2 (hazard ratio [HR], 3.1; p < 0.01), previous revision surgery (HR, 2.8; p < 0.01), and a McPherson host grade of C (HR, 2.5; p = 0.04). The cumulative incidence of aseptic revision for loosening was 2% at 5 years, 5% at 10 years, and 7% at 15 years. Femoral (HR, 5.0; p = 0.04) and tibial (HR, 6.7; p < 0.01) bone-grafting at reimplantation were predictive of aseptic failure. The most common complications were wound-healing issues, requiring reoperation in 12 (5%) of the knees. The rate of death at 2 years following reimplantation was 11%. The mean KSS improved from 45 at PJI diagnosis to 76 at 10 years following reimplantation (p < 0.01). Conclusions: Long-term reinfection rates following 2-stage exchange for PJI after total knee arthroplasty were similar to those of shorter-term reports and were maintained out to 15 years. Mechanical failure rates were low if bone loss was addressed at the time of reimplantation. Improvements in clinical outcomes were maintained at long-term follow-up.

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927. opens in new tab.)

We investigated a cluster of Mycobacterium fortuitum and M. goodii prosthetic joint surgical site infections occurring during 2010–2014. Cases were defined as culture-positive nontuberculous mycobacteria surgical site infections that had occurred within 1 year of joint replacement surgery performed on or after October 1, 2010. We identified 9 cases by case finding, chart review, interviews, surgical observations, matched case–control study, pulsed-field gel electrophoresis of isolates, and environmental investigation; 6 cases were diagnosed >90 days after surgery. Cases were associated with a surgical instrument vendor representative being in the operating room during surgery; other potential sources were ruled out. A tenth case occurred during 2016. This cluster of infections associated with a vendor reinforces that all personnel entering the operating suite should follow infection control guidelines; samples for mycobacterial culture should be collected early; and postoperative surveillance for <90 days can miss surgical site infections caused by slow-growing organisms requiring specialized cultures, like mycobacteria.

Amphotericin B is used for local delivery from polymethylmethacrylate to treat fungal prosthetic joint infections. The optimal amphotericin B formulation and the influence of different poragens in the bone cements are unknown. To investigate the necessary amount of amphotericin B in the bone cement to prevent Candida biofilm several amphotericin B formulations were studied: non-liposomal and liposomal with or without poragen gentamicin. For the non-liposomal formulation, standard bile salt, the sodium deoxycholate, was used and additionally N-methyl-D-glucamine/palmitate was applied. The activity of the released amphotericin B was tested against C. albicans, C. glabrata, C. parapsilosis and C. krusei biofilms with application of the isothermal calorimeter and standard microbiological methods. Compressive strength was measured before and after antifungal elution from the cements. There is less aggregated N-methyl-D-glucamine/palmitate amphotericin B released but its antifungal activity is equivalent with the deoxycholate amphotericin B. The minimum quantity of antifungal preventing the Candida biofilm formation is 12.5 mg in gram of polymer powder for both non-liposomal formulations. The addition of gentamicin reduced the release of sodium deoxycholate amphotericin B. Gentamicin can be added to N-methyl-D-glucamine/palmitate amphotericin B in order to boost the antifungal release. When using liposomal amphotericin B more drug is released. All amphotericin B formulations were active against Candida biofilms. Although compressive strength slightly decreased, the obtained values were above the level of strength recommended for the implant fixation. The finding of this work might be beneficial for the treatment of the prosthetic joint infections caused by Candida spp.