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.

This data set documents data for a publication currently under consideration at Science. It documents data obtained for IODP Site C0023 during IODP Expedition 370. The data include: concentration of microbial cells and concentration of endospores in sediments, concentration and isotopic composition of methane and acetate in interstitial waters.

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.