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.

Background: Antibiotics after spine instrumentation are often extended while the surgical drain is in place, particularly for traumatic injuries. We sought to study if continuing antibiotics past 24 hours affected outcomes. Methods: We performed a retrospective observational study of all patients who underwent spine fixation with hardware and surgical drains for trauma at our institution. We compared the effect of perioperative (≤24 hours of antibiotics) versus prolonged (>24 hours) antibiotics on surgical outcomes. Bivariate and multivariable logistic and linear regression statistics were performed. Results: Three hundred and forty-six patients were included in the analysis. On multivariate analysis, antibiotic duration >24 hours did not predict surgical site infection (odds ratio, 2.68; 95% confidence interval, 0.88-8.10, P = 0.08) or mortality (odds ratio, 0.59; 95% confidence interval, 0.10-3.44; P = 0.56). Conclusions: Continuing antibiotics past 24 hours after traumatic spine instrumentation was not associated with improved outcomes. A prospective study to verify these findings may be warranted.

Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC 90 and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.

BACKGROUND CONTEXT Surgical site infections (SSI) following spine surgery are debilitating complications to patients and costly to the healthcare system. PURPOSE Review the impact and cost effectiveness of 5 SSI prevention interventions on SSI rates in an orthopedic spine surgery practice at a major quaternary healthcare system over a 10-year period. STUDY DESIGN Retrospective observational study. PATIENT SAMPLE All of the surgical patients of the 5 spine surgeons in our department over a 10-year period were included in this study. OUTCOME MEASURES SSI rates per year, standardized infection ratios (SIR) for laminectomies and fusions during the most recent 3-year period, year of implementation, and frequency of use of the different interventions, cost of the techniques. METHODS The SSI prevention techniques described in this paper include application of intrawound vancomycin powder, wound irrigation with dilute betadine solution, preoperative chlorhexidine gluconate scrubs, preoperative screening with nasal swabbing, and decolonization of S. aureus , and perioperative antibiotic administration. Our institution's infection prevention and control data were analyzed for the yearly SSI rates for the orthopedic spine surgery department from 2006 to 2016. In addition, our orthopedic spine surgeons were polled to determine with what frequency and duration they have been using the different SSI prevention interventions. RESULTS SSI rates decreased from almost 6% per year the first year of observation to less than 2% per year in the final 6 years of this study. A SIR of less than 1.0 for each year was observed for laminectomies and fusions for the period from 2013 to 2016. All surgeons polled at our institution uniformly used perioperative antibiotics, Hibiclens scrub, and the nasal swab protocol since the implementation of these techniques. Some variability existed in the frequency and duration of betadine irrigation and application of vancomycin powder. A cost analysis demonstrated these methods to be nominal compared with the cost of treating a single SSI. CONCLUSIONS It is possible to reduce SSI rates in spine surgery with easy, safe, and cost-effective protocols, when implemented in a standardized manner.

Objectives We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI). Methods Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords ‘prosthetic joint’, and ‘tuberculosis’. Results During years 1997–2016, 13 patients (8 males, 5 females, median age 79 years [range, 60–86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4–20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6–32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS). Conclusions M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.

AIMS: The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. PATIENTS AND METHODS: We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. RESULTS: Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p<0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p<0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. CONCLUSION: PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies

Introduction: Management of surgical site infections (SSI) after instrumented spinal surgery remains controversial. The debridement-irrigation, antibiotic therapy and implant retention protocol (DAIR protocol) is safe and effective to treat deep SSI occurring within the 3 months after instrumented spinal surgery. Methods: This retrospective study describes the outcomes of patients treated over a period of 42 months for deep SSI after instrumented spinal surgery according to a modified DAIR protocol. Results: Among 1694 instrumented surgical procedures, deep SSI occurred in 46 patients (2.7%): 41 patients (89%) experienced early SSI (< 1 month), 3 (7%) delayed SSI (from 1 to 3 months), and 2 (4%) late SSI (> 3months). A total of 37 patients had a minimum 1 year of follow-up; among these the modified DAIR protocol was effective in 28 patients (76%) and failed (need for new surgery for persistent signs of SSI beyond 7 days) in 9 patients (24%). Early second-look surgery (≤ 7days) for iterative debridement was performed in 3 patients, who were included in the cured group. Among the 9 patients in whom the modified DAIR protocol failed, none had early second-look surgery; 3 (33%) recovered and were cured at 1 year follow-up, and 6 (66%) relapsed. Overall, among patients with SSI and a minimum 1 year follow-up, the modified DAIR protocol led to healing in 31/37 (84%) patients. Conclusions: The present study supports the effectiveness of a modified DAIR protocol in deep SSI occurring within the 3 months after instrumented spinal surgery. An early second-look surgery for iterative debridement could increase the success rate of this treatment.

BACKGROUND: Periprosthetic joint infection (PJI) is a potentially deadly complication of total joint arthroplasty. This study was designed to address how the incidence of PJI and outcome of treatment, including mortality, are changing in the population over time. METHODS: Primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients with PJI from the 100% Medicare inpatient data set (2005-2015) were identified. Cox proportional hazards regression models for risk of PJI after THA/TKA (accounting for competing risks) or risk of all-cause mortality after PJI were adjusted for patient and clinical factors, with year included as a covariate to test for time trends. RESULTS: The unadjusted 1-year and 5-year risk of PJI was 0.69% and 1.09% for THA and 0.74% and 1.38% for TKA, respectively. After adjustment, PJI risk did not change significantly by year for THA (P = .63) or TKA (P = .96). The unadjusted 1-year and 5-year overall survival after PJI diagnosis was 88.7% and 67.2% for THA and 91.7% and 71.7% for TKA, respectively. After adjustment, the risk of mortality after PJI decreased significantly by year for THA (hazard ratio = 0.97; P < .001) and TKA (hazard ratio = 0.97; P < .001). CONCLUSION: Despite recent clinical focus on preventing PJI, we are unable to detect substantial decline in the risk of PJI over time, although mortality after PJI has declined. Because PJI risk appears not to be changing over time, the incidence of PJI is anticipated to scale up proportionately with the demand for THA and TKA, which is projected to increase substantially in the coming decade.

Background: Culture-negative periprosthetic joint infection (PJI) is a challenging condition to treat. The most appropriate management of culture-negative PJI is not known, and there is immense variability in the treatment outcome of this condition. The purpose of this study was to elucidate the characteristics, outcomes, and risk factors for failure of treatment of culture-negative PJI. Methods: A retrospective review of 219 patients (138 hips and 81 knees) who had undergone surgery for the treatment of culture-negative PJI was performed utilizing a prospectively collected institutional PJI database. PJIs for which the results of culture were unavailable were excluded. An electronic query and manual review of the medical records were completed to obtain patient demographics, treatment, microbiology data, comorbidities, and other surgical characteristics. Treatment failure was assessed using the Delphi consensus criteria. Results: The prevalence of suspected culture-negative PJI was 22.0% (219 of 996), and the prevalence of culture-negative PJI as defined by the Musculoskeletal Infection Society (MSIS) was 6.4% (44 of 688). Overall, the rate of treatment success was 69.2% (110 of 159) in patients with >1 year of follow-up. Of the 49 culture-negative PJIs for which treatment failed, 26 (53.1%) subsequently had positive cultures; of those 26, 10 (38.5%) were positive for methicillin-sensitive Staphylococcus aureus. The rate of treatment success was greater (p = 0.019) for patients who had 2-stage exchange than for those who underwent irrigation and debridement. Conclusions: The present study demonstrates that culture-negative PJI is a relatively frequent finding with unacceptable rates of treatment failure. Every effort should be made to isolate the infecting organism prior to surgical intervention, including extending the incubation period for cultures, withholding antibiotics prior to obtaining culture specimens, and possibly using newly introduced molecular techniques.

Background: Propionibacterium acnes (P. acnes) is the most common bacteria associated with infection after shoulder arthroplasty. These bacteria can be grown on culture of skin after standard preoperative skin preparation and antibiotics. The purpose of this study was to determine whether adding preoperative intravenous doxycycline reduces the prevalence of positive P. acnes cultures of skin and deep tissues at the time of prosthetic joint implantation during shoulder arthroplasty. Methods: This was a randomized controlled trial. An a priori power analysis determined that a sample size of 56 patients was necessary. Patients scheduled to undergo shoulder arthroplasty were randomized to receive either standard perioperative cefazolin or a combination of doxycycline and cefazolin. Tissue specimens for culture were then taken from the skin edge, and swabs of the superficial dermal tissue and glenohumeral joint were obtained. All cultures were maintained for 14 days to allow for P. acnes detection. Groups were compared to determine if the addition of doxycycline reduced the rate of culture positivity. Results: Fifty-six patients were enrolled and randomized. Twenty-one (38%) had ≥1 positive cultures for P. acnes, with no significant difference between the group treated with cefazolin alone (10 [37%] of 27 patients) and the combined doxycycline and cefazolin group (11 [38%] of 29 patients) (p = 0.99). The greatest numbers of culture-positive samples were obtained from the skin (30%), followed by dermal tissue (20%) and the glenohumeral joint (5%). Patients who had ≥1 positive cultures were younger than those who did not (mean age [and standard deviation], 64.9 ± 7.7 versus 69.4 ± 7.7 years; p = 0.041), had a greater tendency to be male (16 [76%] of 21 versus 17 [49%] of 35; p = 0.053), and had a lower Charlson Comorbidity Index (3.35 ± 1.3 versus 4.09 ± 1.4; p = 0.051). There were no significant differences between the culture-positive and culture-negative groups in terms of body mass index (BMI) (p = 0.446) or arthroplasty type, with positive cultures found for 8 of the 29 anatomic shoulder arthroplasty procedures compared with 13 of the 27 reverse shoulder arthroplasty procedures (p = 0.280). There were no doxycycline-related adverse events. Conclusions: In this randomized controlled trial, doxycycline did not significantly decrease P. acnes culture positivity of the skin, dermis, or glenohumeral joint of patients undergoing shoulder arthroplasty. The addition of prophylactic intravenous antibiotics to cover P. acnes may not be an effective method to reduce postoperative and periprosthetic shoulder joint infections.

Background Periprosthetic joint infections (PJI) caused by pathogens, for which no biofilm-active antibiotics are available, are often referred to as difficult-to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse than those of non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a prospective cohort treated with a two-stage exchange according to a standardized algorithm. Methods Patients with hip and knee PJI from 2013 to 2015 were prospectively included and followed up for ≥ 2 years. DTT PJI was defined as growth of microorganism(s) resistant to all available biofilm-active antibiotics. The Kaplan–Meier survival analysis was used to compare the probability of infection-free survival between DTT and non-DTT PJI and the 95% confidence interval (95% CI) was calculated. Results Among 163 PJI, 30 (18.4%) were classified as DTT and 133 (81.6%) as non-DTT. At a mean follow-up of 33 months (range 24–48 months), the overall treatment success was 82.8%. The infection-free survival rate at 2 years was 80% (95% CI 61–90%) for DTT PJI and 84% (95% CI 76–89%) for non-DTT PJI (p = 0.61). The following mean values were longer in DTT PJI than in non-DTT PJI: hospital stay (45 vs. 28 days; p < 0.001), prosthesis-free interval (89 vs. 58 days; p < 0.001) and duration of antimicrobial treatment (151 vs. 117 days; p = 0.003). Conclusions The outcome of DTT and non-DTT PJI was similar (80–84%), however, at the cost of longer hospital stay, longer prosthesis-free interval and longer antimicrobial treatment. It remains unclear whether patients undergoing two-stage exchange with a long interval need biofilm-active antibiotics. Further studies need to evaluate the outcome in patients treated with biofilm-active antibiotics undergoing short vs. long interval.

Spinal implant infection is a rare but significant complication of spinal fusion surgery, and the most common pathogen is Staphylococcus aureus. It is difficult to treat due to this pathogen's biofilm-forming ability and antibiotic resistance. We evaluated the therapeutic outcome of treatments for S aureus spinal implant infections. We retrospectively reviewed all patients with S aureus spinal implant infections at 11 tertiary-care hospitals over a 9-year period. Parameters predictive of treatment failure and recurrence were analyzed by Cox regression. Of the 102 patients with infections, 76 (75%) were caused by methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In all, 83 (81%) patients were managed by debridement, antibiotics, and implant retention (DAIR) and 19 (19%) had their implants removed. The median duration of all antibiotic therapies was 52 days. During a median follow-up period of 32 months, treatment failure occurred in 37 (36%) cases. The median time to treatment failure was 113 days, being <1 year in 30 (81%) patients. DAIR (adjusted hazard ratio [aHR], 6.27; P = .01) and MRSA infection (aHR, 4.07; P = .009) were independently associated with treatment failure. Rifampin-based combination treatments exhibited independent protective effects on recurrence (aHR, 0.23; P = .02). In conclusion, among patients with S aureus spinal implant infections, MRSA and DAIR were independent risk factors for treatment failure, and these risk factors were present in the majority of patients. In this difficult-to-treat population, the overall treatment failure rate was 36%; rifampin may improve the outcomes of patients with S aureus spinal implant infections.