OBJECTIVE Currently, no consensus exists as to whether patients who develop infection of the surgical site after undergoing instrumented fusion should have their implants removed at the time of wound debridement. Instrumentation removal may eliminate a potential infection nidus, but removal may also destabilize the patient’s spine. The authors sought to summarize the existing evidence by systematically reviewing published studies that compare outcomes between patients undergoing wound washout and instrumentation removal with outcomes of patients undergoing wound washout alone. The primary objectives were to determine 1) whether instrumentation removal from an infected wound facilitates infection clearance and lowers morbidity, and 2) whether the chronicity of the underlying infection affects the decision to remove instrumentation. METHODS PRISMA guidelines were used to review the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov databases to identify studies that compared patients with implants removed and patients with implants retained. Outcomes of interest included mortality, rate of repeat wound washout, and loss of correction. RESULTS Fifteen articles were included. Of 878 patients examined in these studies, 292 (33%) had instrumentation removed. Patient populations were highly heterogeneous, and outcome data were limited. Available data suggested that rates of reoperation, pseudarthrosis, and death were higher in patients who underwent instrumentation removal at the time of initial washout. Three studies recommended that instrumentation be uniformly removed at the time of wound washout. Five studies favored retaining the original instrumentation. Six studies favored retention in early infections but removal in late infections. CONCLUSIONS The data on this topic remain heterogeneous and low in quality. Retention may be preferred in the setting of early infection, when the risk of underlying spine instability is still high and the risk of mature biofilm formation on the implants is low. However, late infections likely favor instrumentation removal. Higher-quality evidence from large, multicenter, prospective studies is needed to reach generalizable conclusions capable of guiding clinical practice.

Background A two-stage prosthesis exchange procedure has been the gold standard in surgical treatment of the chronically infected knee arthroplasty so far. This includes 2 surgeries/hospitalizations and an interim period of 2–3 months between surgeries with impaired health, functional status and quality of life of the patients. A one-stage exchange procedure holds many obvious advantages compared to the two-stage approach, but outcomes of a one-stage versus two-stage procedures have never been investigated in a randomized clinical trial. The purpose of this study is primarily to investigate time-adjusted differences in functional status of patients after one-stage versus two-stage revision. Secondary, to report time-adjusted differences in quality of life, complications (including re-revisions due to infection) and mortality. Methods This study is a pragmatic, multi-center, randomized, non-inferiority trial comparing one-stage versus two-stage revision of the infected knee arthroplasty. Seven Danish hospitals are currently participating in the study, but additional hospitals can enter the study if adhering to protocol. Ninety-six patients will be included prospectively. Follow-up will be with PROM-questionnaires and clinical controls up to 10 years. The patients who are not able to participate in the randomized trial are followed in a parallel cohort study. PROM’s Oxford Knee Score and EQ5D + EQ5D VAS questionnaires are completed preoperatively and sent out to the study participants at 6 weeks, 3, 6, 9, 12, 18 and 24 months as well as 5 and 10 years postoperatively. In addition a tailor made cost questionnaire on the non-treating hospital resource use, community health and social service use, travel costs, time off work and informal care are sent out. Discussion If one of the two treatment alternatives is found superior in both domains of quality of life (both knee-specific and generic) and health economics, that treatment should be promoted. Other outcomes will open informed discussions about treatment strategies for periprosthetic knee infections. Trial registration The randomized trial is registered on ClinicalTrials.gov with ID NCT03435679, initial release date January 31, 2018 and the cohort study is registered with ID NCT04427943, submitted January 8, 2020 and posted June 11, 2020.

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.

Background One percent to 8% of patients undergoing spinal instrumentation surgeries develop infections. There is no consensus on the medical and surgical management of these infections. Methods We conducted a retrospective chart review based on International Classification of Diseases, Ninth Revision, and Common Procedural Terminology codes relevant to spinal infections with hardware within Emory Healthcare over a 10-year period. Extracted data included patient demographics, clinical presentation, laboratory and microbiologic results, and surgical and medical management including choice and duration of suppressive therapy. Multivariable logistic regression was used to assess the association of length of use of suppressive antibiotics with treatment success and to identify predictors of use of suppressive antibiotics. Results Of 869 records, 124 met inclusion criteria. Fifty patients (40.3%) had an infection that occurred after hardware placement, mostly within 3 months postsurgery, while the remainder had vertebral osteomyelitis that required hardware placement. After initial intravenous antibiotic treatment for ≥4 weeks, 72 patients (64.5%) were given suppressive antibiotics. The overall treatment success rate was 78.2%. In spinal infections involving hardware with gram-negative rods, patients were less likely to receive suppressive antibiotics, less likely to have hardware removed, and less likely to have treatment success compared with patients with infections with Staphylococcus species. Conclusions Management of spinal infections involving hardware should be tailored to the timing of onset of infection and causative organism. Further studies are needed to determine best management practices, particularly for gram-negative rod infections where the role of further suppressive antibiotics and hardware removal may be warranted.

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.

Background The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death. Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates. Methods This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years. Discussion VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected. Trial registration Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529 .

Aims To evaluate the histopathological examination of peri-implant tissue samples as a technique in the diagnosis of postoperative spinal implant infection (PSII). Methods This was a retrospective analysis. Patients who underwent revision spinal surgery at our institution were recruited for this study. PSII was diagnosed by clinical signs, histopathology, and microbiological examination of intraoperatively collected samples. Histopathology was defined as the gold standard. The sensitivity for histopathology was calculated. A total of 47 patients with PSII and at least one microbiological and histopathological sample were included in the study. Results PSII occurred in approximately 28% of the study population. Histopathology showed a sensitivity of 51.1% in the diagnosis of PSII. The most commonly found pathogens were Cutibacterium acnes and gram-positive staphylococci. Conclusion Histopathology has low sensitivity for detecting PSII. In particular, infections caused by low-virulence microorganisms are insufficiently detected by histopathology. Cite this article: Bone Joint J 2020;102-B(7):899–903.

In July of 2018, the Second International Consensus Meeting (ICM) on Musculoskeletal Infection convened in Philadelphia, PA was held to discuss issues regarding infection in orthopedic patients and to provide consensus recommendations on these issues to practicing orthopedic surgeons. During this meeting, attending delegates divided into subspecialty groups to discuss topics specifics to their respective fields, which included the spine. At the spine subspecialty group meeting, delegates discussed and voted upon the recommendations for 63 questions regarding the prevention, diagnosis, and treatment of infection in spinal surgery. Of the 63 questions, 9 focused on implants questions in spine surgery, for which this article provides the recommendations, voting results, and rationales.

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.