Aim. Prosthetic joint infection (PJI) due to Candida spp. is a severe complication of arthroplasty but is little reported. This study describes Candida PJI epidemiology, management, and outcome. Method. We performed a retrospective, observational multinational study with support of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Patients diagnosed with PJI due to Candida spp. between 1990 and 2021 were included. Demographic, clinical, laboratory, imaging, medical/surgical treatment, and outcome data were collected within a standardized database. Treatment failure was defined either as a Candida infection recurrence, superinfection, or death due to infection. Results. Data from 151 patients across 18 centers were analyzed. Mean age was 69.5 ± 13.1yo, 78 (51.7%) patients were male, and 21 (13.9%) were immunosuppressed. Site of infection included hip (55.0%), knee (41.7%), shoulder (2.6%), and femur (0.7%). Twenty-five (16.6%) patients were febrile, and 58 (38.4%) had fistula. Mean number of previous surgeries on the same anatomical site was 3.3±2.3. Surgeries were DAIR (33.8%), one-stage exchange (19.9%), two-stage exchange (39.1%), and implant removal (6.0%). Candida species identified were C. albicans (60.3%), C. parapsilosis (26.5%), C. glabrata (7.3%), and C. tropicalis (5.3%). Co-infection with bacteria was found in 69 (45.7%) cases. Fluconazole (62.9%) and caspofungin (14.6%) were the main antifungal agents prescribed for 148.6 ± 167.5 days. Favorable outcome was found in 54/144 (37.5%) cases. Failure was associated with the number of previous surgeries (OR 1.249, 95%CI 1.061–1.469; p-value=0.007), while treatment by fluconazole was associated with cure (OR 0.336, 95%CI 0.160–0.707; p-value=0.004). Conclusions. This study provides epidemiologic and outcome data on Candida PJIs. Although poor overall, the prognosis did not seem associated with immunosuppression, type of surgery, fungal species or treatment duration

Aim. Fast and accurate identification of pathogens causing periprosthetic joint infections (PJI) is essential to initiate effective antimicrobial treatment. Culture-based approaches frequently yield false negative results, despite clear signs of infection. This may be due to the use of general growth media, which do not mimic the conditions at site of infection. Possible alternative approaches include DNA-based techniques, the use of in vivo-like media and isothermal microcalorimetry (ITC). We developed a synthetic synovial fluid (SSF) medium that closely resembles the in vivo microenvironment and allows to grow and study PJI pathogens in physiologically relevant conditions. In this study we investigated whether the use of ITC in combination with the SSF medium can improve accuracy and time to detection in the context of PJI. Methods. In this study, 120 synovial fluid samples were included, aspirated from patients with clinical signs of PJI. For these samples microbiology data (obtained in the clinical microbiology lab using standard procedures) and next generation sequencing (NGS) data, were available. The samples were incubated in the SSF medium at different oxygen levels (21% O. 2. , 3% O. 2. and 0% O. 2. ) for 10 days. Every 24h, the presence of growth was checked. From positive samples, cultures were purified on Columbia blood agar and identified using MALDI-TOF. In parallel, heat produced by metabolically active microorganisms present in the samples was measured using ITC (calScreener, Symcel), (96h at 37°C, in SSF, BHI and thioglycolate). From the resulting thermograms the ‘time to activity’ could be derived. The accuracy and time to detection were compared between the different detection methods. Results. So far, seven samples were investigated. Using conventional culture-based techniques only 14.3% of the samples resulted in positive cultures, whereas NGS indicated the presence of microorganisms in 57.1% of the samples (with 3/7 samples being polymicrobial). Strikingly, 100% of the samples resulted in positive cultures after incubation in the SSF medium, with time to detection varying from 1 to 9 days. MALDI-TOF revealed all samples to be polymicrobial after cultivation in SSF, identifying organisms not detected by conventional techniques or NGS. For the samples investigated so far, signals obtained with ITC were low, probably reflecting the low microbial load in the first set of samples. Conclusion. These initial results highlight the potential of the SSF medium as an alternative culture medium to detect microorganisms in PJI context. Further studies with additional samples are ongoing; in addition, the microcalorimetry workflow is being optimized

Aim. To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum. Method. The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 10. 4. CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 10. 4. CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed. Results. The separation of aggregates into different size fractions was done successfully by the filtering method. Isothermal microcalorimetry showed, a delayed Time-to-peak metabolic activity of the aggregate-inoculum compared to the planktonic inoculum. S. aureus was isolated from subcutis, bone and implants from all animals in groups A and B. Both group A animals showed osteomyelitis at gross inspection with suppuration and sequestration, while groups B and C animals had no macroscopic lesions. From CT scans, both group A animals also showed positive signs of osteomyelitis, i.e., osteolysis, while only one animal in group B did, and none in group C. Histopathological examination of the bones showed more extensive inflammation in group A animals compared to those in group B, which showed more osteoid formation. Conclusions. Formation and separation of low metabolism bacterial aggregates into different size fractions was possible. The aggregates can be used as inoculum in the porcine IAO model, with microbiological re-isolation from both implants and tissue. Furthermore, the aggregates caused a less aggressive IAO, than the planktonic counterparts. Using aggregated bacteria as inoculum appears to be more relevant to the clinical situation of infecting bacteria

Aim. Bone and joint infections (BJIs) are serious infections requiring early optimized antimicrobial therapy. BJIs can be polymicrobial or caused by fastidious bacteria, and the patient may have received antibiotics prior to sampling, which may decrease the sensitivity of culture-based diagnosis. Furthermore, culture-based diagnosis can take up to 14 days. Molecular approaches can be useful to overcome these concerns. The BioFire® system performs syndromic multiplex PCR in 1 hour, with only a few minutes of sample preparation. The BioFire® Joint Infection (JI) panel (BF-JI), recently FDA-cleared, detects both Gram-positive (n=15) and Gram-negative bacteria (n=14), Candida, and eight antibiotic resistance genes directly from synovial fluids. The aim of this study was to evaluate its performance in acute JIs in real-life conditions. Method. BF-JI was performed on synovial fluid from patients with clinical suspicion of acute JI, either septic arthritis or periprosthetic JI, in 6 French centers. The results of BF-JI were compared with the results of culture of synovial fluid and other concomitantly collected osteoarticular samples obtained in routine testing in the clinical microbiology laboratory. Results. From July 2021 to May 2022, 319 patients (including 10 children < 5y and 136 periprosthetic infections) had been included in the study. The BF-JI test was invalid for one patient (not retested). Among the 318 remaining patients, overall concordance with comparative microbiology methods was 88% (280/318): 131 samples were negative with both BF-JI and culture, and 149 samples were positive with the same microorganisms using complementary techniques. In 33 cases (10.4%), BF-JI was negative while culture was positive: 18 microorganisms were not targeted by BF-JI (including Staphylococcus epidermidis, n=10, and Cutibacterium acnes, n=2); 15 microorganisms targeted by BF-JI were obtained in culture but not by the molecular test (false-negative 4.7%). In 20 cases, BF-JI was positive while culture was not: 12 patients had received antibiotics before sampling, and 7 cases involved fragile and fastidious bacteria (Kingella kingae, n=5; Neisseria gonorrhoeae, n=2). In 6 cases, both BF-JI and culture were positive, but no yielding the same bacteria (polymicrobial specimens). Conclusions. In acute JIs, the BF-JI panel shows a good concordance with culture for the microorganisms targeted by the panel. Therefore, this molecular tool may have a place in microbiological diagnosis of acute JIs in order to confirm JI faster than culture. Moreover, it allows easy detection of difficult-to-culture bacteria. Acknowledgements. study was supported by bioMérieux, who provided all reagents

Aim. Periprosthetic Joint Infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The “JS BACH” classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The “JS BACH” classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand. Method. We applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use. Results. Individual cases were classified as per JS-BACH into “1 - uncomplicated” (n = 268), “2 - complex” (n = 330), and “3 - limited options” (n = 55). This cohort was similar to the original JS-BACH population in terms of baseline characteristics. However, there was a difference in complexity, with more DAIR procedures, fewer revision procedures, and a higher proportion of uncomplicated patients in the PIANO cohort. The risk of treatment failure correlated strongly with the JS-BACH category, with odds ratios (95% CI [confidence interval]) for category 2 versus 1 of 1.75 (1.24 to 2.47) and for category 3 versus 1 of 7.12 (3.42 to 16.02). Conclusions. Despite the PIANO study population being less complicated than the original derivation cohort, the JS-BACH classification showed a clear association with treatment failure in this large external cohort

This study aimed to identify the success rate of debridement, antibiotics and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict DAIR success was assessed. A prospective, multicenter study of PJIs occurring between July 2014 and December 2017 in 27 hospitals across Australia and New Zealand was performed. First time PJIs following primary TKA that were managed with DAIR were analyzed. DAIR success was defined as the patient being alive with documented absence of clinical or microbiological evidence of infection and no ongoing antibiotics for the index joint at 2-year follow-up. Multivariate analysis was performed for multiple PJI classification systems to assess their ability to predict DAIR success using their respective definitions of “early” PJI (Coventry ≤1 month, International Consensus Meeting ≤90 days or Auckland <1 year), or as hematogenous versus chronic PJI (Tsukayama). 189 PJIs were managed with DAIR, with an overall success rate of 45% (85/189). Early PJIs had a higher rate of DAIR success when analyzed according to the Coventry system (adjusted odds ratio = 3.85, p = 0.008), the ICM system (adjusted odds ratio = 3.08, p = 0.005) and the Auckland system (adjusted odds ratio = 2.60, p = 0.01). DAIR success was lower in both hematogenous (adjusted odds ratio = 0.36, p = 0.034) and chronic PJIs (adjusted odds ratio = 0.14, p = 0.003) occurring more than one year since the primary TKA. DAIR success is highest when performed in infections occurring within one year of the primary TKA. Late infections had a high DAIR failure rate irrespective of their classification as hematogenous or chronic. Time since primary is a useful predictor of DAIR success

The optimum indications for debridement, antibiotics and implant retention (DAIR) are unclear. Previous studies have demonstrated higher success rate of DAIR within one year of the primary arthroplasty. This study aimed to compare the success rate of DAIR vs revision in “early” and “late” infections to provide guidance for clinical decision making. The Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort prospectively recorded PJIs between July 2014 and December 2017 in 27 hospitals. This study included PIANO patients with first time PJIs occurring after primary TKA. Treatment success was defined as the patient being alive, free from further revision and without clinical or microbiological evidence of reinfection at two years follow-up. “Early” and “late” infections were analyzed separately. Univariate analysis compared demographic and disease specific factors between the DAIR and Revision groups. Multivariate binary logistic regression identified whether treatment strategy and other risk factors were associated with treatment success in “early” and “late” infections. In 117 “early” (<1 year) infections, treatment success rate was 56% in the DAIR group and 54% in the revision group (p=0.878). No independent risk factors were associated with treatment outcome on multivariate analysis. In 134 “late” (>1 year) infections, treatment success rate was 34.4% in the DAIR group and 60.5% in the revision group (OR 3.07 p=0.006). On multivariate analysis, revision was associated with 2.47x higher odds of success (p=0.041) when compared to DAIR, patients with at least one significant co-morbidity (OR 2.27, p=0.045) or with Staphylococcus aureus PJIs (OR 2.5, p=0.042) had higher odds of failure. In “late” PJIs occurring >1 year following primary TKA, treatment strategy with revision rather than DAIR was associated with greater success. Patients with significant comorbidities and Staphylococcus aureus PJIs were at higher risk of failure regardless of treatment strategy

Aim. dalbavancin, a lipo-glycopeptide antibiotic effective against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus), allows extended dosing interval due to its peculiar pharmacokinetics. Despite being registered for treatment of acute skin infections, off-label use has shown promise in various settings, particularly in osteo-articular infections. This study aims to assess dalbavancin's pharmacological efficacy and its safety and clinical success in patients treated according to personalized schedules guided by Therapeutic Drug Monitoring (TDM), particularly in long-term therapies. Methods. non-interventional, retrospective, single-center pharmacological study. We included adult patients with at least one dalbavancin TDM determination from July 1, 2022 to February 1, 2024 and treated with outpatient parenteral antimicrobial therapy. We recorded dalbavancin trough concentration (Cmin) and its peak concentration (Cmax) and employed log-linear regression models to predict the timing of dalbavancin dosing, aiming to sustain Cmin levels above 4 or 8.04 mg/L, according to recent literature. Data regarding index infections, patients’ characteristics, outcomes, and adverse events were also collected. Results. we included 32 patients, whose clinical and microbiological characteristics are depicted in Table 1. Regarding the primary outcome, 132/134 (98.5%) trough concentration was >4 mg/L, while 112/134 (83.6%) was >8.04 mg/L. For the secondary outcomes, 2/32 patients experienced an adverse event correlated to dalbavancin: (i) exanthema one week after the start of therapy and (ii) exanthema, conjunctivitis, angioedema, and nausea one month after the start of therapy. Moreover, we observed 4/32 clinical unsuccess (one failure during treatment, one relapse after the end of therapy, one switch to another antibiotic, and one isolation of non-susceptible microorganism). Conclusions. a TDM-based approach with the use of a log-linear regression model allows a more precise timing of dalbavancin administration by maintaining sufficient concentration of circulating drugs. This approach is promising for infections requiring a long-term treatment, such as orthopedic infection where source control is not possible. For any tables or figures, please contact the authors directly

Aim. Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method. All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included:. Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral. Antibiotic Team (OPAT). Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results. Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin. The reasons for choosing dalbavancin over alternatives were due to either:. Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7). OR. Convenience to avoid the need for OPAT (8). Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits. Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome. Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions. Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aim. Vancomycin is frequently used for bone and joint infections (BJI) because of the main role of Gram-positive bacteria as potential causal agents. It is crucial to achieve optimal vancomycin plasma concentrations since the first day to maximize treatment clinical and microbiological efficacy. The aim was to describe the patients’ profile that are more likely to achieve an optimal pharmacokinetic/pharmacodynamics (PK/PD) vancomycin target in the first therapeutic drug monitoring (TDM) sample. Methods. Retrospective study (March 2018-January 2022) in a university hospital including all patients treated with vancomycin for a BJI and undergoing TDM. Initial dose (1g/8-12h) was selected by the responsible clinician. Vancomycin plasma concentrations were obtained pre-dose (Cmin,ss) and 60-minutes after the infusion on day 2 of treatment. Global exposure measured by the area under the curve of plasma concentrations during 24h (AUC024h) was estimated using a bicompartmental PK model. An AUC024h/CMI=400–600mg*h/L was considered optimal, <400 infratherapeutic and >600 supratherapeutic, based on recent guidelines, and patients were classified into these 3 groups. A value of CMI=1 mg/L was considered, following guidelines recommendations. Categorial data: percentages and quantitative data as mean (standard deviation). Results. Ninety-five patients were included: 22(23.2%), 43(45.3%) and 30(31.6%) presented an infratherapeutic, optimal and supratherapeutic PKPD target, respectively. Medium age was 75,8(13,5) in the supratherapeutic group versus 57,2(16,3) in the infratherapeutic group. Weight (kg) was higher in the infratherapeutic group 80,8(18,4) versus 66,8(15,5) in the supratherapeutic group. Vancomycin dose (mg/kg/d) was 43,5(12,4) in the supratherapeutic group versus 34,5(10,8) in the infratherapeutic group. There were 17(56,7) patients who received 1g/8h of vancomycin in the supratherapeutic group and 6 (27,3) in the infratherapeutic group. Baseline glomerular filtration rate (BGF (CKD-EPI) (mL/min/1.73m2) was 71,5(20,1) in the supratherapeutic group and 100,0 (19,9) in the infratherapeutic group. The AUC24h/CMI was 788,0(186,1) in the supratherapeutic group and 323,7(55,4) in the infratherapeutic group. Significant differences observed in age, body weight (BW), baseline renal function and dose/frequency of vancomycin. Dosage adjustments recommendations were made in 62(65.3%) patients: 31(32.6%) dose-increase, 29(30.5%) reduction and 2 cases (2.1%) a temporary suspension. Conclusions. Less than 50% of patients achieved an optimal exposure of vancomycin on day 2 of treatment. Patients with infratherapeutic levels had a younger age and a higher body weight and glomerular filtration rate. In addition, they had received a lower vancomycin initial dose. On the contrary, a potentially toxic exposure was observed within older patients with impaired baseline renal function. These data suggest the relevance of an early vancomycin TDM for optimizing the treatment of BJI

Aims. Periprosthetic fungal infections are rare and account for 1–2% of all periprosthetic joint infections (PJI). This study aims at presenting treatment details, clinical and microbiological results in a large single centre cohort. Methods. We retrospectively identified 29 patients (9 total knee replacements (TKA) and 20 total hip replacements (THA) treated for a fungal infection between 2007 and 2019. Microbiological findings, patient demographics and complications were analysed. Statistical analysis was performed using descriptive statistics; non-parametric analysis were performed using the Mann-Whitney U-Test. Infection-free survival was determined using Kaplan-Meier analysis and differences in survival were analysed using the log-rank test. The p value was set at p<0.05 with 95% confidence intervals (95% CI) provided. Results. 28% (8/29) suffered from reinfection. The reinfection-free survival probability was 65% (95% CI 45–85) after a median follow- up period of 28 months (IQR 6 – 39). With the numbers we had, we were not able to detect a difference between THA and TKA re-infections (p=0.517). Four patients underwent amputation, 3 patients had a definitive girdlestone hip and eight patients died after a median of 5 months after first-stage surgery (IQR 1–7). All patients treated had positive synovial fluid or tissue cultures for Candida species. In 22 /29 patients C. albicans, in 3 patients C. parapsilosis, in 2 patients C. glabrata and in 1 patient each C. famata, C. dubliniensis and C. gulliermondii. Polymicrobial bacterial infection was found in 86% of patients with staphylococci in 20 patients, E. coli in 2 patients, vancomycin-resistant enterococci, pseudomonas, acinetobacter and achromobacter species in 1 patient each. When investigating risk factors for reinfection, with the numbers we had we were not able to find a significant difference for patients with polymicrobial infection (p=0.974), azole-resistant Candida (p=0.491), tobacco users (p=0.175), or diabetics (p=0.54). Furthermore, median age (73 vs. 72, p=0.756) and Charlson comorbidity score (6 (interquartile range (IQR) 4–8) vs. 8 (IQR 5–10), p=0.184) were not different between the groups while on the other hand there was a trend for a higher body mass index in patients with reinfection (34 (IQR 31–38) vs. 28 (IQR 25–33), p=0.075). Conclusions. Fungal PJI is associated with poor reinfection free survival, frequent revisions, and high mortality. All infections were caused by Candida spp. in which azole-resistance most be considered when planning treatment. While polymicrobial infection complicated treatment there was no difference in survival. A higher BMI and comorbidity score might be associated with higher risk for reinfections

Aim. Bone and joint infections (BJI) are associated with a heavy morbidity and high health costs. Comorbidities, device associated infections and complicated journeys are associated with increased mortality, treatment failures and costs. For this reason, 24 referral centers (RC) have been created in 2009 in order to advise about management of “complex” BJI in weekly multidisciplinary meetings (MM). Since end of 2012, data from these meetings are gathered in a national database. We aimed to describe the data from this French registry of BJI and determine factors associated with the definition of “complex” BJI. Method. Demographic, clinical, microbiologic and therapeutic characteristics of patients are systematically recorded in the database. Data from the first presentation in RC for each adult patients are presented. Complexity of BJI is recorded after each meeting according to 4 criteria (first failure, complex antibiotic therapy, precarious underlying conditions or complex surgical procedure). Part of unavailable data have been completed by pattern extraction from text-encoded commentaries. Factors associated with complexity were determined by multivariate logistic regression. Results. From 2012 to 2016, 17.527 patients were included corresponding to 30.300 presentations in MM. Median age was 64 years (IQR 50–76) with masculine predominance (61.8%). Comorbidity was present in 50.3%, with at least 2 comorbidities in 26%. Prosthetic joint infection represented 41.4% of patients, followed by chronic osteitis with/without foreign material (24%). Definite microbiologic documentation was available in 68.8% of cases, mostly Staphylococcus aureus (43.9%) followed by Coagulase negative Staphylococci (28.6%) and enterobacteriaceae (23.1%), with 27.4% of polybacterial infections. Antibiotic treatment was proposed in 81.6% and surgery in 70% of cases. BJI were defined as complex in 55.4%, mostly because underlying conditions (50%), and in 57.6% with at least 2 complexity criteria. Factors positively associated with definition of complexity in MM were: background: number of comorbidities, immunodeficiency, neoplasia, liver or kidney failure, intra-cardiac device; microbiology: Mycobacteria, Fungus, MRSA, MSSA, MR-CoNS, MDR enterobacteria, non-fermentative BGN, and atypical pathogens (actinomycetes, nocardia, intra-cellular …); infection characteristics: prosthetic joint infection, osteitis, foreign material infection, arthritis and number of infected sites; surgical procedures: surgical flap, 2 stages prosthesis exchange, spacer, arthrodesis, and joint removal. Simple debridement was negatively associated with complex definition. Conclusions. This registry is the first national prospective database about management of BJI in France and provide many information about epidemiology and management of BJI in France, as well as a more precise definition of complexity

Aim. Obese patients are not only more likely to receive total joint arthroplasty, but are also more prone to postoperative complications. The most severe complication is a prosthetic joint infection (PJI), occurring two to four times more often in severely obese patients (BMI ≥ 35kg/m. 2. ) compared to non-obese patients. This higher risk for PJI may be attributed to higher glucose levels in case of diabetes mellitus, diminished wound healing or inadequate antibiotic prophylaxis. To ultimately improve the prevention measures for this specific patient category, we aimed to describe the clinical and microbiological characteristics of early acute PJI in severely obese patients. Method. We retrospectively evaluated patients with early acute PJI of the hip and knee treated with DAIR between 2006 and 2016 in three Dutch hospitals. According to protocol, cefazolin was administered as antibiotic prophylaxis during arthroplasty and adjusted to bodyweight. PJI was diagnosed using the criteria described by the Musculoskeletal Infection Society. Early acute PJI was defined as less than 21 days of symptoms and a DAIR performed within 90 days after index surgery. Several clinical and microbiological variables were collected and analyzed. Severe obesity was defined as a BMI ≥ 35kg/m. 2. . Results. A total of 356 patients were analyzed, including 73 severely obese patients (20.5%). Compared to patients with a BMI < 35kg/m. 2. , severely obese patients were relatively young (69 years vs 74 years, p=0.001), female (75.3% vs 56.9%, p=0.005), with PJI of the knee (35.6% vs 20.8%, p=0.025) and arthroplasty indicated for osteoarthritis (87.7% vs 63.3%, p=0.001). They had higher incidences of diabetes mellitus (34.2% vs 18.7%, p=0.005) and hypertension (74.0% vs 59.0%, p=0.021). Severely obese patients had more often polymicrobial infections (67.4% vs 45.7%, p=0.009) and higher rates of infection with Enterococcus species (37.0% vs 15.8%, p=0.002) and Gram-negative rods, such as Proteus species (17.4% vs 2.3%, p<0.001). This finding was most prominent in hips, comprising Gram-negative PJIs in 32.6% of severely obese patients compared to 18.1% in non-severely obese patients (p=0.030). There were no differences in the number of infections due to Staphylococcus aureus or Staphylococcus epidermidis. Conclusions. Our results demonstrate that severely obese patients with early acute PJI have higher rates of polymicrobial infections with involvement of Gram-negative rods and enterococci, especially in the hip region. Our data stress the importance of improving preventive strategies in this specific patient category, which may entail extension of antibiotic prophylaxis to a broader Gram-negative and Gram-positive coverage

Aim. Periprosthetic joint infection (PJI) is a major complication of prosthetic implantation and needs a combined surgical and antimicrobial treatment. One-stage revision results usually in similar cure rate than two-stage (around 85–92%), but antibiotic therapy duration is not well established. The aim of study was to evaluate the efficacy of a short six-weeks antibiotic course in hip and knee PJIs after one-stage replacement arthroplasty (RA). Method. This was a retrospective, observational study conducted at Orthopaedic Department of Cochin Hospital, Paris, between 1stJanuary 2010 and 31 December 2015. Inclusion criteria were: age>18 years; clinical/microbiological diagnosis of PJI; one-stage RA; 6-weeks course of antibiotics; follow-up of at least one year. PJIs were classified depending on the delay of infection from implantation as: early(<3 months), delayed(3–24 months), late(>24 months). Pearson's-χ2 and t-tests were used to compare categorical and continuous variables. Results. Fifty patients with PJIs treated with one-stage hip/knee replacement arthroplasty (HRA/KRA) were included, 42 HRA, 8KRA. Median age was 69.3 years (IQR 24.5–97.4), 31 were males. Comorbidities included tumours(18%), polyarthritis(12%), chronic kidney disease (CKD), HIV infection. ASA score was ≥3 in 15(30%) cases. PJIs occurred after a mean of 36 months:9 early, 9 delayed, 32 late. Bone biopsy and synovial fluid cultures were positive for methicillin-susceptible coagulase-negative Staphylococci (MSCNS) in 19(65%) cases, methicillin-resistant CNS (MRCNS) in 5(17%), methicillin-susceptible S. aureus (MSSA) in 5(17%), P. acnes in 20(40%), Enterobacteriacae in 6(12%), Streptococcus spp. in 4(8%), E. faecium and Listeria spp.(2%). Twelve PJIs (24%) were polymicrobial. Intravenous antibiotics were administered for 11 days (IQR 4–45). Daptomycin was used in 22(44%) cases. Forty-six 46(92%) patients were switched to oral antibiotics: fluoroquinolones in 25(54%) cases, clindamycin in 19(41%), beta-lactams in 17(37%), rifampicin in 12(26%). One patient died due to a carcinoma, while others reached at least one year evaluation (IQR 12–60). Overall, the remission rate was 90%(HRA=90%, KRA=88%). Failures included 4 relapses and one reinfection: HRA in 80%, ASA score ≥3 in 40%. Infections recurred after 6 months (IQR 4–12); bacteria involved were: MSCNS(n=2), MSSA, P. acnes and ESBL-producing K. pneumoniae. Univariate analysis, performed for demographical and PJI parameters, showed no differences between success and failures, except for radiotherapy, HIV infection and CKD associated to worst prognosis (p=0.05, OR=10.7; remission rate=50%). The lowest rate of failures was observed with rifampicin use, but it was not significant(p=0.14). Conclusions. six-weeks course of antibiotics in knee and hip PJIs treated with one stage revision, seems sufficient with a satisfactory remission rate

Aim. To conduct a systematic review of non-rodent animal models (rabbit, pig, dog, goat and sheep) of bone infection. In the future, anti-infective technologies aiming to fight bone infections are depending on evaluation in reliable animal models. Therefore, it is highly relevant to evaluate the scientific quality of existing bone infection models. Method. PubMed and Web of Science were searched systematically. To be included in the systematic review, publications had to deal with bacterial inoculation of non-rodent animals in order to model bone infections in humans. Data was extracted on study design e.g. bacterial inoculation dose and infection time, methodological quality and post-mortem evaluation with respect to registration and quantification of pathology and microbiology. Results. In total, 316 publications were included in the systematic review. A substantial lack of study design information (e.g. bacterial identity and infection time) was demonstrated in many of the papers, which hampers reproducibility and continuation of the established work. Furthermore, the methodological study quality was found to be low as definition of infection, randomization, power analysis and blinding were only seldom reported. The use of histology has increased in recent years, but a semi-quantitative scoring of the lesions was often missing, i.e. no objective quantification of outcome. Most of the studies focused on whether the inoculated bacteria were present within the bone tissue post mortem or not. However, very often the bacterial burden was not quantified. In many of the models, different antimicrobial interventions were examined, and the lack of quantitative microbiology makes it difficult to estimate and reproduce the effects objectively. Although, antimicrobial effects were described for most interventions, a lack of sterile outcome was observed in many models. Failure to report a sterile outcome reduces the possibility for obtaining valuable knowledge regarding effective antibiotic doses in-vivo. Based on the present review a standard study template guideline for animal models of bone infections was established. The guideline describes details related to the animal, pathogen, animal + pathogen (infected animal) and post mortem analysis that are of crucial importance for validation of results and reproducibility. Conclusions. Due to a substantial lack of uniformity we miss the opportunity to get maximal knowledge from the preclinical literature. The new guideline will improve reproducibility of future models and translation of findings to the clinical setting. Bone infection organisations/societies and journal editors should encourage compliance with the new guideline. Reference: JBJS, 2019, In press

Implementation of new diagnostic methods (i.e. MALDI-TOF MS) has made it possible to identify coagulase-negative staphylococci (CoNS) to species level in routine practice. Further knowledge about clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different CoNS may both facilitate interpretation of microbiological findings and improve clinical algorithms. The aim of this study was clinical and microbiological characterization of PJIs caused by Staphylococcus capitis. Patients with PJIs caused by S. capitis (growth in ≥2 perioperative tissue samples, n=19, identified by MALDI-TOF MS) from three centres between 2005–2014 were included. Medical records were examined (n=16). Further characterization of S. capitis was performed; rep-PCR (Diversilab, BioMerieux), standard antibiotic susceptibility testing, GRD Etest and macromethod Etest for detection of heteroresistant subpopulations and microtitre plate assay for detection of biofilm production. Multi-drug resistant (MDR) S. capitis (R≥3 antibiotic groups) was detected in 5/19(26%) of isolates, 1/19(5%) were ciprofloxacin resistant and no isolates was rifampin resistant. Biofilm formation was present in 14/19(74%). The dendrograms created by rep-PCR showed two distinct clusters, including one that contained isolates from all centres, as well as the reference isolates. Furthermore, three additional clusters were identified, all of these mainly obtained from single centres. In two of these, MDR was highly prevalent. In one of these clusters, 4 of the 8 strictly monomicrobial infections were found. All of the PJIs were defined as either early postinterventional (10/16) or chronic (6/16). No late haematogenous infection was found. The highest CRP values were reported in monomicrobial infections. Wound healing disturbances was noted in 8/10 early postinterventional infections. Fever was absent in chronic infections, sinus tracts rare (1/6), while pain was a common symptom (5/6). S. capitis has the potential to cause PJIs, both by itself as well as part of a polymicrobial infection. The antibiotic susceptibility patterns were more favourable than has previously been reported in S. epidermidis isolated from PJIs(1). Clinical data suggests that PJIs caused by S. capitis were acquired perioperatively or in the early postoperative phase. The clustering found by rep-PCR together with data showing high prevalence of S. capitis in the air of operation rooms during prosthetic joint surgery(2) implicates that nosocomial spread might be present. Epidemiological surveillance may be of value in order to ensure early detection of nosocomial transmission. Grants were received from the research committees of Värmland County Council and Örebro University, Sweden

Aim. Gram negative bacteria (GNB) are emerging pathogens in chronic post-traumatic osteomyelitis. However, data on multi-drug (MDR) and extensively drug resistant (XDR) GNB are sparse. Methods. A multi-centre epidemiological study was performed in 10 countries by members of the ESGIAI (ESCMID Study Group on Implant Associated Infections). Osteosynthesis-associated osteomyelitis (OAO) of the lower extremities and MDR/XDR GNB were defined according to international guidelines. Data from 2000 to 2015 on demographics, clinical features, microbiology, surgical treatment and antimicrobial therapy were retrospectively analyzed. Cure was assessed after the end of treatment as the absence of any sign relevant to OAO. Factors associated with cure were evaluated by regression analysis. Results. A total of 53 infections of OAO of the lower extremities (hip, femur, tibia) were evaluated. Patients were female (n=32, 60.4%), with a mean age (SD) 57(3) years, history of trauma (83%), comorbidities (26.4%). The most frequent GNB were: E.coli (n=15), P.aeruginosa (n=14), Klebsiella spp (n=8), Enterobacter spp (n=8) and Acinetobacter spp (n=5). P.aeruginosa predominated the XDR group than the MDR one (n=6/10 vs n=8/43, p=0.01). Antibiotics were given mostly in combinations (64%) for a median duration of 117 days (SD:31.5). Carbapenems were the most frequently used agents (54.7%), followed by colistin (18.8%) and fluoroquinolones (15%). Surgical treatment included debridement with implant retention (n=22), implant explantation (n=22), new osteosynthesis (n=3), others(n=6). Only failure of the surgical treatment for OAO was associated with lack of cure [OR 8.924 (CI95%: 3.006–26.495), p<0.001] at the end of treatment, for a 12-month follow-up period. Patients' age, gender, comorbidities, history of trauma and surgery, clinical presentation of OAO, type of antimicrobial treatment (use of fluoroquinolones, carbapenems or colistin as monotherapy or in combination) as well as type of surgical intervention (explantation vs implant retention) were not found to significantly influence the patients' outcome. Overall, cure was assessed in 31 patients (58.5%). Death occurred in 7 patients, all older than 60, with failure of surgical treatment (p=0.016). These patients presented with many comorbidities (57%) and without difference in treatment outcome between XDR and MDR infection (p=0.114). Conclusion. Osteosynthesis-associated infections of the lower extremities caused by MDR/XDR GNB are a severe complication in orthopaedic surgery. The role of surgical treatment is independently associated with outcome regardless of the type of intervention (explantation or implant retention) and the type of antimicrobial treatment

Aim. Over the past three years, roughly 100,000 hip and knee replacements have been performed by the Brazilian Public Healthcare System. Prosthetic joint infection (PJI) is expected to range between 1% to 10% after primary and revisions joint arthroplasties, respectively. So far, there have been no published national PJI data which would be helpful at developing local preventive strategies and guide surgeons and clinicians. We aimed at describing the epidemiological, clinical and microbiological PJI results of a national and collaboration study among infectious diseases specialists and orthopaedic surgeons, including academic, public and private institutions. Method. We prospectively enrolled patients with PJI in a national cohort study among 12 hospitals from 6 different States to describe host, pathogens, diagnosis, surgery strategies adopted (according to the standard hospital-based guideline) and outcome after 1- and 2-years follow-up. PJI was defined using the IDSA criteria (Osmon D, et al. Clin Infect Dis. 2013). Patients were enrolled from July 2013 to December 2015. Results. Overall, 234 patients undergoing hip, knee and shoulder (n=3) arthroplasty were eligible; 35 were excluded: did not fulfil the inclusion criteria (n=14), withdrawal informed consent (n=11) and early lost to follow-up (n=10). A total of 199 were available for analysis. Twenty-two (11%) patients died during the follow-up, most of which (95%) occurred within 1 year of PJI diagnosis. In the one-year (12 patients lost to follow-up) and two-year (18 patients lost to follow-up) post-diagnosis analysis, overall treatment failure occurred in 13.3% (n=22/166), and 17% (n=25/147). Knee and hip rate failure in the 1- and 2-year follow up were 12.2% (n=9/74), 15.4% (n=14/91), and 16.2% (n=11/68), 18.2% (n=14/77), respectively. Debridement with implant retention (DAIR), one-stage exchange, two-stage exchange, and arthrodesis was performed in 44.7%, 25.4%, 22.3%, 7.6% respectively. Failure rates for DAIR, one-stage exchange, two-stage exchange, and arthrodesis after 1- and 2-year follow-up were 24.2% (n=16/66), 4.3% (n=2/46), 9.8% (4/41), 0% (n=0/15), and 28.6% (n=16/56), 4.8% (n=2/42), 15.8% (n=6/38), 0% (n=0/15), respectively. Microbial diagnosis yielded positive culture in 71.7%. Staphylococcus aureus (34%), coagulase-negative staphylococci (28%), Pseudomonas aeruginosa (17%) were more prevalent. Polymicrobial PJI were diagnosed in 32.8%. Conclusions. This is so far the largest Brazilian cohort of patients with PJI showing an overall 2-years failure-free survival rate of 83%, in which DAIR is the most frequent and less successful strategy, single-stage exchange seems to be a growing surgical option. Polymicrobial and non-fermenting Gram-negative bacilli and Enterobacteriacae is frequent

Aim. Data on Prosthetic joint infection (PJI) caused by multi-drug resistant (MDR) or XDR (extensively drug resistant) Gram negative bacteria (GNB) are limited. Treatment options are also restricted. We conducted a multi-national, multi-center assessment of clinical data and factors of outcome for these infections. Method. PJI were defined upon international guidelines. Data from 2000–2015 on demographics, clinical features, microbiology, surgical treatment and antimicrobial therapy was collected retrospectively. Factors associated with treatment success were evaluated by logistic regression analysis. Results. A total of 133 PJI were evaluated. Female (n=84, 61.4%) and the elderly [mean age (+/-SD) 73 (12.7)] predominated. Diabetes mellitus was the most frequent comorbidity (n=42,32.1%) followed by rheumatoid arthritis (n=14,10.7). Most PJI were early infections (84.4 %). XDR accounted for 23 cases; half of them due to Pseudomonas aeruginosa. Prevalence of MDR or XDR GNB was not different between early and late PJIs (p=0.114). Overall, P.aeruginosa (n=25, 19.1%) was followed by Klebsiella spp (n=23,17.6%) and Enterobacter spp (n=22,16.8%). PJI was located at the hip (n=85 65.6%), knee (n=41,31.3%), shoulder (n=3,2.3%) and ankle (n=1, 0.8%). Clinical characteristics included soft tissue infection (66.4%), pain (51.1%), fever (32.1%) and sinus tract(29.8%). Surgery for PJIs consisted of DAIR (debridement, antibiotics and implant retention), (n=64, 49.6%), followed by explantation of the arthroplasty (n=32, 24.8%), two-stage revision (n=16, 12,4%), one stage revision (n=9, 7%), arthrodesis (n=2, 1.6%). Median duration of antibiotic therapy was 51 days (IQR 25–75: 40–90 days). Cure after treatment was assessed in 78 patients (58.6%). No-DAIR surgical procedures in PJIs were more likely to be successful compared to DAIR surgery (75.8% vs 50%, OR 3.13, 95% CI:1.47–6.70, p=0.003)both in early or late infections. Conclusions. PJI by MDR/XDR GNB affects female, the elderly with comorbidities and previous surgery for PJI. P.aeruginosa is frequent, mostly XRD. No-DAIR procedures have higher probability of treatment success than DAIR even in early infection. Despite surgery and long-term antimicrobial administration, treatment success was less than 60%, probably reflecting the lack of effective treatment options