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.

Study Design. A retrospective cohort study. Objective. The aim of this study was to assess hospital resource utilization and costs associated with Staphylococcus aureus infection within 180 days post elective posterior instrumented spinal fusion surgeries (index surgery) between 2010 and 2015. Summary of Background Data. Surgical site infections (SSIs) and blood stream infections (BSIs) post spinal fusion surgeries are associated with worse clinical outcomes and increased costs. Economic data specific to the most common pathogen of infections post spinal fusion surgeries, S. aureus, are limited. Methods. We analyzed hospital discharge and microbiology data from 129 U.S. hospitals in Premier Healthcare Database. Selection criteria included age ≥ 18 years; had a primary/secondary ICD-9-CM procedure code for index surgery; and had microbiology data during study period. Outcomes included total hospitalization cost, length of stay, and risk of all-cause readmission. Infection status was classified as culture-confirmed invasive ( i.e. , BSIs, deep or organ/space SSIs), any, and no S. aureus infection. Multivariable regression analyses were used to compare outcome variables between infection groups controlling for known confounders. Results. Two hundred ninety-four patients had any S. aureus infection (151 had invasive infection) and 12,918 had no infection. Compared with no infection group, invasive and any infection groups had higher total hospitalization cost (adjusted mean in 2015 U.S. dollars: $88,353 and $64,356 vs . $47,366, P  < 0.001), longer length of stay (adjusted mean: 20.98 and 13.15 vs . 6.77 days, P  < 0.001), and higher risk of all-cause readmission [adjusted risk ratio: 2.15 (95% confidence interval: 2.06–2.25) for invasive and 1.70 (95% confidence interval: 1.61–1.80) for any infection groups]. Conclusion. S. aureus infections post elective posterior instrumented spinal fusion surgeries are associated with significantly higher hospitalization cost, length of stay, and 180-day risk of readmission than those with no such infection, which presents substantial burden to hospitals and patients. Reducing such infections may cut costs and hospital resource utilization. Level of Evidence: 3

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.)

The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of osteomyelitis when biopsied, and magnetic resonance imaging may not accurately distinguish osteomyelitis from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and osteomyelitis is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the osteomyelitis is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy.

The study aims to determine whether 8 weeks of antibiotics is non-inferior to 12 weeks in patients with acute deep spinal implant infection (SII). In the retrospective study of all SII cases (2009-2016), patients aged ≥ 15 years with microbiologically confirmed SII treated with debridement and implant retention were included. Whenever possible, tailored antibiotic treatment was used: rifampin/linezolid in gram-positive and quinolones in gram-negative infection. Patients were divided into short treatment course (8 weeks, ST group) and extended treatment (12 weeks, ET group). Primary outcome measure was percentage of cures at 1-year follow-up. One-hundred-twenty-four patients considered, 48 excluded based on the above criteria, leaving 76 patients, 28 ST and 48 ET. There were no differences in patient age, comorbidities, underlying pathologies, infection location, or surgery characteristics between groups. Surgery-to-debridement time was similar (18.5-day ST vs. 19-day ET; P = 0.96). Sixteen SII cases (21.1%) occurred with bloodstream infection. Pathogens found were Enterobacteriaceae (35, 46.1%), Staphylococcus aureus (29, 38.2%), coagulase-negative staphylococci (12, 15.8%), Pseudomonas aeruginosa (12, 15.8%), and Enterococcus faecalis (7, 9.2%). Twenty seven (35.5%) had polymicrobial infection. E. faecalis was more frequent in the ST group (7, 25% vs. 0; P < 0.001), and P. aeruginosa in ET (1, 3.6% vs. 11, 22.9%; P = 0.05). Five patients died of causes unrelated to SII. At 1-year follow-up, cure rates (21/26 ST, 80.8% vs. 39/45 ET, 86.7%; P = 0.52) and recurrences (2/26, 7.7% vs. 2/45, 4.4%; P = 0.62) were similar. Eight-week antimicrobial courses were not inferior to 12 weeks in patients with acute deep SII treated with prompt debridement, proper wound healing, and optimized antibiotics.

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.

Abstract Background Orthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4–6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance. Methods SOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis. Discussion This study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship. Trial registration Clinicaltrials.gov, NCT03806166 . Registered on 11 November 2019.

Background: Periprosthetic joint infection (PJI) is the leading cause of early revisions after total knee arthroplasty. Debridement, antibiotics, and implant retention (DAIR) procedures are often the initial treatment for PJI. However, there is concern that failed DAIR undermines the future success of revision procedures. This study aims to investigate the impact of DAIR on the success of subsequent staged revisions for PJI. Methods: A multicenter retrospective review was performed over a 15-year period. Treatment success was defined as implant retention without the use of long-term suppressive antibiotics. This was compared between patients who underwent a staged revision as the first procedure for PJI (staged-only) and patients who failed DAIR before staged revision (F-DAIR). Competing risk survival analysis was performed to compare the 2 groups and considered for patient demographics, American Society of Anesthesiologists score, organism type, body mass index, age of prosthesis, and duration of symptoms. Results: Of 291 eligible patients, 63 underwent staged revision and 228 underwent DAIR as the first procedure for PJI. Of the 228 DAIR patients, 75 failed DAIR and underwent subsequent staged revision (F-DAIR). At mean follow-up of 6.2 years, the success rate was 72% in the F-DAIR group and 81% in the staged-only group. On survival analysis, there was no significant difference in subdistribution hazard ratio comparing the probability of failure (implant retention) in the 2 treatments groups (subdistribution hazard ratio = 0.72; 95% confidence interval 0.32-1.61; P = .42). Conclusion: This study suggested that a previously failed DAIR does not compromise the success rate of a subsequent staged revision.