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.

Abstract Purpose Biofilm-active antibiotics are suggested to improve the outcome of implant-associated infections; however, their role in infections after spinal instrumentation is unclear. Therefore, we evaluated the outcome of patients with spinal implant-associated infections treated with and without biofilm-active antibiotics. Methods The probability of infection-free survival was estimated for treatment of spinal implant-associated infections with and without biofilm-active antibiotics using the Kaplan–Meier method; Cox proportional-hazards regression model was used to identify factors associated with treatment failure. Results Among 93 included patients, early-onset infection was diagnosed in 61 (66%) and late-onset in 32 infections (34%). Thirty patients (32%) were treated with biofilm-active antibiotic therapy and 63 (68%) without it. The infection-free survival after a median follow-up of 53.7 months (range, 8 days-9.4 years) was 67% (95% confidence interval [CI], 55–82%) after 1 year and 58% (95% CI 43–71%) after 2 years. The infection-free survival after 1 and 2 years was 94% (95% CI 85–99%) and 84% (95% CI 71–93%) for patients treated with biofilm-active antibiotics, respectively, and 57% (95% CI 39–80%) and 49% (95% CI 28–61%) for those treated without biofilm-active antibiotics, respectively (p = 0.009). Treatment with biofilm-active antibiotics (hazard ratio [HR], 0.23, 95% CI 0.07–0.77), infection with Staphylococcus auras (HR, 2.19, 95% CI 1.04–4.62) and polymicrobial infection (HR, 2.44, 95% CI 1.09–6.04) were significantly associated with treatment outcome. Severe pain was observed more often in patients without biofilm-active antibiotic therapy (49% vs. 18%, p  = 0.027). Conclusion Treatment with biofilm-active antibiotics was associated with better treatment outcome and less postoperative pain intensity.

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.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients’ short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.

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 The incidence of spinal surgical site infections (SSIs) remains stable at less than 10%. Surgical reinterventions may be hampered by decubitus, treatment-related adverse events, and cost. In the context of emergence of bacterial resistance, a short duration of antimicrobial treatment is of critical importance. If the duration of treatment for SSI is currently 12 weeks, the aim of our study was to assess the efficacy of an antimicrobial treatment shortened to 6 weeks. Methods This prospective study was carried out from November 2014 to July 2016 in an 827-bed teaching hospital. After surgical management of SSIs, patients received broad-spectrum antibiotics intravenously for 10 days and orally for the remainder, for a total of 6 weeks. Success was defined as absence of relapse, superinfection, or surgical failure at the end of treatment and at 1-year follow-up. Results Eighty-five patients were included in this study. The median delay between initial surgery and diagnosis of SSI was 16 days. In 65 cases (76.4%), SSIs were monomicrobial; among these, Staphylococcus aureus was found in 30 cases (46%). Failure was observed in 7 cases (8.2%), with more than half caused by anaerobic bacteria. Conclusions Surgical management of SSI followed by a 6-week antibiotic treatment is associated with favorable outcome. Anaerobic bacteria seem to play a role in the occurrence of relapses. A 6-week reduction in antibiotic treatment leads to reduction in cost and, likely, also to reduction in the emergence and spread of resistant microorganisms.