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: 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.)

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.

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.

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.

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.

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.

Background Failed total knee arthroplasty (TKA) with significant bone loss and compromised soft-tissues is challenging and the final results are often inferior to patient’s expectation. The objective of this study was to present a comparison of outcomes in patients with failed infected TKA treated with two-stage revision TKA or knee arthrodesis and to assess clinical and functional results, implant survival and infection recurrence. The hypothesis was that an arthrodesis may result in beneficial effects on patients’ outcome. Methods Clinical data of 81 patients with periprosthetic joint infection (PJI) of the knee joint were collected and analyzed retrospectively. Between 2008 and 2014, a total of 36 patients had been treated within a two-stage exchange procedure and reimplantation of a modular intramedullary arthodesis nail and 45 patients with revision TKA. Patients were treated according to the same structured treatment algorithm. Clinical and functional evaluation was performed using the Oxford knee score (OKS) and the visual analogue scale (VAS). Results The mean follow-up was 32.9 ± 14.0 months. The rate of definitely free of infection at last follow-up in the arthrodesis group was 32 of 36 (88.9%) and 36 of 45 (80.0%) in the revision TKA group (p = 0.272). Mean VAS for pain in the arthrodesis group was 3.1 ± 1.4 compared to 3.2 ± 1.6 in the revision TKA group (p = 0.636). The OKS in the arthrodesis group was 38.7 ± 8.9 and 36.5 ± 8.9 (p = 0.246) in patients with revision TKA. Rate of revisions in the revision-TKA group was 2.8 ± 3.7 compared to 1.2 ± 2.4 in the arthrodesis group (p = 0.021). Conclusion Treatment of PJI needs a distinct therapy with possible fallback strategies in case of failure. A knee arthrodesis is a limb salvage procedure that showed no significant benefits on the considered outcome factors compared to revision TKA but is associated with significantly lower revision rate. After exhausted treatment modalities, a knee arthrodesis should be considered as an option in selected patients.

Aims Periprosthetic joint infection (PJI) remains a challenging complication following total hip arthroplasty (THA). It is associated with high levels of morbidity, mortality and expense. Guidelines and protocols exist for the management of culture-positive patients. Managing culture-negative patients with a PJI poses a greater challenge to surgeons and the wider multidisciplinary team as clear guidance is lacking. Patients and Methods We aimed to compare the outcomes of treatment for 50 consecutive culture-negative and 50 consecutive culture-positive patients who underwent two-stage revision THA for chronic infection with a minimum follow-up of five years. Results There was no significant difference in the outcomes between the two groups of patients, with a similar rate of re-infection of 6%, five years post-operatively. Culture-negative PJIs were associated with older age, smoking, referral from elsewhere and pre-operative antibiotic treatment. The samples in the culture-negative patients were negative before the first stage (aspiration), during the first-stage (implant removal) and second-stage procedures (re-implantation). Conclusion Adherence to strict protocols for selecting and treating culture-negative patients with a PJI using the same two-stage revision approach that we employ for complex culture-positive PJIs is important in order to achieve control of the infection in this difficult group of patients.

Background In total knee arthroplasty (TKA) periprosthetic joint infection (PJI), irrigation and debridement (I&D) with component retention is a treatment option with a wide variation in reported failure rates. The purpose of this study was to determine failure rates, outcomes, and factors that predict failure in I&D for TKA PJI. Methods A multicenter observational study of patients with a TKA PJI and subsequently undergoing an I&D with retention of components was conducted. The primary outcome was failure rate of I&D, where failure was defined as any subsequent surgical procedures. Results Two hundred sixteen cases of I&D with retention of components performed on 206 patients met inclusion criteria. The estimated long-term failure rate at 4 years was 57.4%. Time-to-event analyses revealed that the median survival time was 14.32 months. Five-year mortality was 19.9%. Multivariable modeling revealed that time symptomatic and organism were independent predictors of I&D failure. Culture-negative status had a higher hazard for failure than culture-positive patients. When primary organism and time symptomatic were selected to produce an optimized scenario for an I&D, the estimated failure rate was 39.6%. Conclusion I&D with retention of components has a high failure rate, and there is a high incidence of more complex procedures after this option is chosen. The patient comorbidities we investigated did not predict I&D success. Our results suggest that I&D has a limited ability to control infection in TKA and should be used selectively under optimum conditions.