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Background: Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI., Methods: Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used., Results: During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452)., Conclusions: Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments., (© 2021. The Author(s).)

Objectives: Nationwide study on the epidemiology, clinical characteristics and outcomes among patients with native joint infection (NJI) in Iceland, 2003-2017., Methods: All positive synovial fluid culture results in Iceland were identified and medical records reviewed., Results: A total of 299 NJI (40 children and 259 adults) were diagnosed in Iceland in 2003-2017, with a stable incidence of 6.3 cases/100 000/year, but marked gender difference among adults (33% women vs 67% men, p<0.001). The knee joint was most commonly affected, and Staphylococcus aureus was the most common isolate in both adults and children, followed by various streptococcal species in adults and Kingella kingae in children. NJI was iatrogenic in 34% of adults (88/259) but comprised 45% among 18-65 years and a stable incidence. Incidence of infections following arthroscopic procedures in adults increased significantly compared with the previous decade (9/100 000/year in 1990-2002 vs 25/100 000/year in 2003-2017, p<0.01) with no significant increase seen in risk per procedure. The proportion of postarthroscopic NJI was 0.17% overall but 0.24% for knee arthroscopy. Patients with postarthroscopic infection were more likely to undergo subsequent arthroplasty when compared with other patients with NJI (p=0.008)., Conclusions: The incidence of NJI in Iceland has remained stable. The proportion of iatrogenic infections is high, especially among young adults, with an increase seen in postarthroscopic infections when compared with the previous decade. Although rare, NJI following arthroscopy can be a devastating complication, with significant morbidity and these results, therefore, emphasise the need for firm indications when arthroscopic treatment is considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Beyond intracellular penetration, acidic lysosomal pH might affect the intracellular activity of some antimicrobials. This study evaluated the ability of lysosomotropic alkalizing agents to potentiate the antimicrobial eradication of an intra-osteoblastic Staphylococcus aureus reservoir in the setting of bone and joint infection (BJI)., Methods: MICs of 16 anti-staphylococcal molecules active against methicillin-sensitive S. aureus (MSSA) were evaluated at pH 5 and pH 7. Additionally, the lysosomal alkalizing potential (spectrofluorometry) and cytotoxicity (MTT assay) of hydroxychloroquine, amantadine and ammonium chloride were assessed. The results led to further investigation of clindamycin, cotrimoxazole, daptomycin and levofloxacin-alone or in combination with hydroxychloroquine-in an in vitro model of osteoblast infection. The impact of hydroxychloroquine on autophagy was finally investigated using Western blot detection of two autophagic flux indicators, the LC3 membrane protein and the SQSTM1 cargo protein., Results: Daptomycin, cotrimoxazole, clindamycin and levofloxacin alone significantly decreased the intracellular staphylococcal reservoir (5.12 log 10  CFU/100 000 cells) by 0.14 (95%CI 0.01-0.34), 0.25 (95%CI 0.12-0.43), 0.16 (95%CI 0.004-0.39) and 1.18 (95%CI 1.04-1.38) log 10  CFU/100 000 cells, respectively (p < 10 -3 ). Adding hydroxychloroquine (20 mg/L) increased intralysosomal pH from 4.8 to 7, and concomitantly the inoculum of each antimicrobial was reduced by 0.50 (95%CI 0.30-0.84), 0.73 (95%CI 0.59-0.96), 0.59 (95%CI 0.46-0.78) and 1.8 (95%CI 1.66-2.1) log 10  CFU/100 000 cells, respectively (p < 10 -4 ). Cellular levels of LC3II and SQSTM1 showed that hydroxychloroquine has direct activity on the autophagic flux, fostering the eradication of intracellular S. aureus by antimicrobials., Conclusion: At high concentrations, hydroxychloroquine used as an adjuvant to antimicrobials improves eradication of an S. aureus intra-osteoblastic reservoir in our in vitro cell infection model. These findings advocate further in vivo evaluation of alkalization efficacy and tolerance in S. aureus BJI., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration., Methods: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route., Results: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC 0-8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively., Conclusion: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture., Methods: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB., Primary Outcome: early-PJI after HHA., Results: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10])., Conclusions: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this study was to evaluate antimicrobial therapy outcomes of bone and joint infections (BJI) caused by Clostridium perfringens. We investigated remission of symptoms and the absence of relapse or reinfection during follow-up. Among the 8 patients with C. perfringens BJI, the type of infection was early prosthesis infection (n = 2), osteosynthetic device infection (n = 4), and chronic osteomyeletis (n = 2). Clindamycin-rifampicin combination was given in 4 cases and metronidazole in 4 cases. The overall success rate was 87.5%. Among the 7 patients who completed antibiotic treatment, the success rate was 100%. The clindamycin-rifampicin combination appeared to be effective in patients with C. perfringens BJI., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The progress of diagnostic strategies and molecular methods improved the detection of Kingella kingae in bone and joint infections, and now, Kingella kingae is being increasingly recognized as the most frequent cause of bone and joint infection BJI in early childhood. The main objective of this prospective study is to report the frequency of Kingella Kingae in negative culture bone and joint pediatric infections, and to describe the clinical and biologic features of these children., Methods: From December 2016 to June 2019, we selected all hospitalized patients with suspected BJI. When culture was negative on the fifth day, children under 10 years were subsequently included in the study, and PCR assay was performed systematically for researching K. kingae specific gene cpn60. Microbial culture and identification were made using standard bacteriological methods. The demographics, clinical, laboratory, radiographic and clinical features were reviewed from medical records., Results: We enrolled 65 children with culture negative BJI, 46 of them having under 10 years old have been screened for the cpn60 gene. Thus, the gene encoding Kingella kingae was positive for 27 BJI cases (58.7%). The mean age of children was 3.02 years, 55.6% were aged 6 months-4 years and 29.6% of them were aged 5-10 years. The male to female ratio was 1.7 and 16 cases (59.26%) occurred during the fall-winter period. The most frequent BJI type was septic arthritis (77.8%) and the most affected sites were knee (51.9%) and hip (37.0%). We recorded a mild clinical picture with normal to mildly raised inflammatory markers. All patients had good clinical and functional outcomes, with no serious orthopedic sequelae.., Conclusion: K kingae is an important pathogen of culture-negative BJI in Moroccan children. PCR testing should be performed in culture-negative cases of children not only in the typical age range of 6 months to 4 years. When implemented in the routine clinical microbiology laboratory, a specific K. kingae PCR assay can provide a better diagnostic performance of BJI., (© 2021. The Author(s).)

Objectives: The management of bone and joint infections (BJI) is complex and requires prolonged antimicrobial therapy. Few data exist on adherence to anti-infectious treatment other than HIV, and none on BJI, even though compliance is considered as a major determinant of clinical outcome. This work aimed at evaluating adherence to oral antimicrobial treatment in patients with BJI., Patients and Methods: This is a prospective observational blinded pilot study evaluating adherence by a 6-item questionnaire at 6 weeks (W6) and 3 months (M3) post-surgery. The primary endpoint was the proportion of patients with high, moderate and poor adherence at W6. Secondary endpoints included change in adherence between W6 and M3, and the exploration of potential variables influencing adherence., Results: Analysis was performed on 65 questionnaires obtained from 43 patients including 35 with device-associated BJI. At W6, 11 out of 34 patients were highly adherent to oral antibiotic therapy, 22 moderately adherent and 1 poorly adherent. There was no significant change in adherence to antibiotic therapy between W6 and M3. The only variable significantly associated with the level of adherence at W6 and M3 was the number of daily doses of antibiotic (P=0.04 and 0.02 at W6 and M3, respectively)., Conclusions: This study provided a snapshot of patients' adherence in BJI. Adherence to antibiotic therapy appeared to be stable up to 3 months and a higher number of daily doses of antibiotic was associated with poorer adherence. These observations need to be confirmed in future large-scale studies using electronic pill monitoring systems., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: The management of prosthetic joint infection requires a complex treatment procedure and can be associated with complications. However, the occurrence of severe adverse events during this intervention has been poorly evaluated., Patients and Methods: A 5-year multicentric retrospective study including patients from 3 hospitals in the South-Western France referral center for complex bone and joint infections (Crioac GSO) and treated for hip or knee prosthetic joint infection with 1 or 2-stage implant exchanges. The objective was to describe grade≥3 adverse events, according to the CTCAE classification, occurring within 6 weeks after surgery and to identify their associated factors., Results: One hundred and eighteen patients were identified. We observed 71 severe events in 50 patients (42.3%; 95% confidence interval [CI95%]: 33.8-51.4%). Sixteen severe events were an evolution of the infection. The remaining 55 others (47 grade 3 and 8 grade 4) occurred in 41 patients (34.7%; CI95%: 26.8-43.7%). They were distributed as follows: 27 (49.1%) medical complications, 21 (38.2%) surgical complications and 7 (12.7%) antibiotic-related complications. The main identified risk factor was a two-stage prosthetic exchange with OR=3.6 (CI95% [1.11-11.94], P=0.032). Obesity was limit of significance with OR=3.3 (CI95% [0.9-12.51], P=0.071). Infection with coagulase negative Staphylococcus was a protective factor with OR=0.3 (CI95% [0.12-0.99], P=0.047)., Conclusion: Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The diagnosis of prosthetic joint infections and isolation of causative microorganisms has been found to be challenging in microbiology laboratories due to low sensitivity of microbiological culture. The aim of this study was to compare the use of conventional culture methods with the use of both enrichment broth and BacT/ALERT paediatric blood culture bottles, for the diagnosis of prosthetic joint infections. A total of 121 specimens from 44 patients were processed using three methods of microbiological culture: solid media, enrichment broth and paediatric bottles. The paediatric bottle method had a significantly lower (p<0.0001) time to detection than the standard solid media method, and was significantly more sensitive than solid media when used independently (93.33%, CI 83.27-98.09, vs 60.00%, CI 45.43-73.33). The combination use of solid media with paediatric bottles was found to be superior to the conventional solid media method and combination use with enrichment broth., (Copyright © 2020 Royal College of Pathologists of Australasia. All rights reserved.)

Pathogen identification is a critical step during diagnosis of infectious diseases. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF-MS) has become the gold standard for identification of microorganisms cultured on solid media in microbiology laboratories. Direct identification of microbes from liquid specimen, circumventing the need for the additional overnight cultivation step, has been successfully established for blood culture, urine and liquor. Here, we evaluate the ability of MALDI-TOF MS for direct identification of pathogens in synovial fluid after liquid enrichment in BacT/Alert blood culture bottles. Influence of synovial specimen quality on direct species identification with the MALDI BioTyper/Sepsityper was tested with samples inoculated from pretested native synovia with concomitant inoculation of blood or pus, or highly viscous fluid. Here, we achieved >90% concordance with culture on solid medium, and only mixed-species samples posed significant problems. Performance in routine diagnostics was tested prospectively on bottles inoculated by treating physicians on ward. There, we achieved >70% concordance with culture on solid media. The major contributors to test failure were the absence of a measurable mass signal and mixed-specimen samples. The Sepsityper workflow worked well on samples derived from BacT/Alert blood culture bottles inoculated with synovial fluid, giving concordant results to identification from solid media. Host remnant material in the inoculum, such as blood or pus, had no detrimental effect on identification score values of the BioTyper system after processing with the Sepsityper workflow, and neither had the initial viscosity of the synovial sample., Competing Interests: The authors have declared that no competing interests exist.

Background: The innate immune system can recall previous immunologic challenges and thus respond more effectively to subsequent unrelated challenges, a phenomenon called trained immunity. Training the innate immune system before surgery might be a potential option to prevent bone and joint infection., Questions/purposes: (1) Does the training process cause adverse effects such as fever or organ injury? (2) Does training the innate immune system confer broad-spectrum protection against bone and joint infection in a mouse model? (3) Does trained immunity remain effective for up to 8 weeks in this mouse model?, Methods: After randomization and group information blinding, we trained the innate immune system of C57BL/6 mice (n = 20 for each group) by intravenously injecting them with either 0.1 mg of zymosan (a toll-like receptor 2 agonist), 0.1 mg of lipopolysaccharide (a toll-like receptor 4 agonist), or normal saline (control). For assessing the host response and possible organ injury after training and infection challenge, we monitored rectal temperature, collected blood to determine leukocyte counts, and performed biochemical and proinflammatory cytokine analyses. After 2 weeks, we then assessed whether trained immunity could prevent infections in an intraarticular implant model subjected to a local or systemic challenge with a broad spectrum of bacterial species (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes, or Pseudomonas aeruginosa) in terms of culture-positive rate and colony counts. The proportion of culture-positive joint samples from trained and control groups were compared after 4 weeks. Finally, we increased the interval between training and bacterial challenge up to 8 weeks to assess the durability of training efficacies., Results: Training with zymosan and lipopolysaccharide caused mild and transient stress in host animals in terms of elevated rectal temperature and higher blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels. Trained mice had fewer culture-positive joint samples after local inoculation with S. aureus (control: 100% [20 of 20]; zymosan: 55% [11 of 20], relative risk 0.55 [95% CI 0.37 to 0.82]; p = 0.001; lipopolysaccharide: 60% [12 of 20], RR 0.60 [95% CI 0.42 to 0.86]; p = 0.003) and systemic challenge with S. aureus (control: 70% [14 of 20]; zymosan: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001; lipopolysaccharide: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001) than controls. We observed similar patterns of enhanced protection against local and systemic challenge of E. coli, E. faecalis, S. pyogenes, and P. aeruginosa. Zymosan-trained mice were more effectively protected against both local (control: 20 of 20 [100%], zymosan: 14 of 20 [70%], RR 0.70 [95% CI 0.53 to 0.93]; p = 0.02) and systemic (control: 70% [14 of 20]; zymosan: 30% [6 of 20], RR 0.43 [95% CI 0.21 to 0.89]; p = 0.03) challenge with S. aureus for up to 8 weeks than controls., Conclusions: Trained immunity confers mild stress and broad-spectrum protection against bone and joint infection in a mouse model. The protection conferred by immunity training lasted up to 8 weeks in this mouse model. The results of the current research support further study of this presurgical strategy to mitigate bone and joint infection in other large animal models., Clinical Relevance: If large animal models substantiate the efficacy and safety of presurgical immunity training-based strategies, clinical trials would be then warranted to translate this strategy into clinical practice.

Introduction: Periprosthetic joint infection (PJI) is one of the most complex complications following total joint arthroplasty. Despite significant progress in recent years, the use of blood and synovial biomarkers to diagnose PJI remains a challenge., Areas Covered: A combination of serological, synovial, microbiological, histological, and radiological investigations is suggested by consensus and international guidelines. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the biomarkers used to diagnose PJI and highlight their sensitivity and specificity. In addition, guidance on the diagnostic steps and clinical workflow will be included., Expert Opinion: The diagnostic algorithm developed and validated by the international consensus meeting group is still the most valuable resource to approach PJI diagnosis. The current combination of blood and synovial biomarkers yield acceptable results and good performance. However, there is a need for new biomarkers and further research to understand the limitations of current tests better, as well as explore new options such as alpha-defensin, D-dimer, interleukin-6, and leukocyte esterase.

Bone and joint infections (BJI) of the lower limb can cause functional sequelae and in some cases have an impact on patient's life prognostic. One of the main objectives of multidisciplinary consultation team meetings (MTM) in the treatment of bone and joint infections is to provide an appropriate medical-surgical care, pooling skills of different organ specialists: infectious disease physicians, microbiologists, orthopedic surgeons and plastic surgeons. Treatment is based on aggressive debridement, bone stabilization, adequate antibiotic therapy, long-term coverage of the loss of skin substance and close clinical monitoring. The authors present their multidisciplinary diagnostic and therapeutic approaches to BJI complicating an open fracture at a referent center in the management of complex bone and joint infections., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: Sonication of explanted prosthesis constitutes an element of microbiological diagnostics. The aim of performing this procedure is to remove biofilm and to increase sensitivity of diagnostics. Ultrasound used in medical purposes are low-frequency and low-intensity. With this wide range of frequency which can be used in sonication process it is necessary to find the golden mean between biofilm dislodging and planktonic bacteria sparing., Materials and Methods: The aim of this study was to determine the least harming low-intensity ultrasound frequency (35 kHz, 40 kHz or 53 kHz) used during sonication process with other parameters constant. Four bacteria species were examined: S. aureus, E. faecalis, E. coli, K. pneumoniae. Number of microbiological studies (n) for each group (g) counted 40 specimens (based on scheme 1 bacteria type - 4 groups, 40 studies each)., Results: A detailed analysis of gathered data was conducted. Based on study findings following conclusions were drawn. Sonication has a significant and negative impact on survival of sonicated planktonic bacteria. Part of bacteria in planktonic state are damaged/killed by ultrasound, which is demonstrated by lower CFU count in sonicated samples versus control group., Conclusions: Optimal ultrasound frequencies for sonication of S. aureus, P. aeruginosa and E. coli are 35 kHz and 40 kHz. Ultrasound frequencies used in sonication process (35 kHz, 40 kHz, 53 kHz) of E. coli showed same impact on bacteria survival. It is crucial to perform further assessment of ultrasound parameters on clinical effects of sonication used in PJI diagnostics., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa., Methods: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin., Results: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments)., Conclusions: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.

Lyme disease, caused by Borrelia burgdorferi, B. afzelii and B. garinii, is a chronic, multi-systemic infection and the spectrum of tissues affected can vary with the Lyme disease strain. For example, whereas B. garinii infection is associated with neurologic manifestations, B. burgdorferi infection is associated with arthritis. The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components fibronectin and/or dermatan sulfate in an OspC variant-dependent manner. Murine infection by isogenic B. burgdorferi strains differing only in their ospC coding region revealed that two OspC variants capable of binding dermatan sulfate promoted colonization of all tissues tested, including joints. However, an isogenic strain producing OspC from B. garinii strain PBr, which binds fibronectin but not dermatan sulfate, colonized the skin, heart and bladder, but not joints. Moreover, a strain producing an OspC altered to recognize neither fibronectin nor dermatan sulfate displayed dramatically reduced levels of tissue colonization that were indistinguishable from a strain entirely deficient in OspC. Finally, intravital microscopy revealed that this OspC mutant, in contrast to a strain producing wild type OspC, was defective in promoting joint invasion by B. burgdorferi in living mice. We conclude that OspC functions as an ECM-binding adhesin that is required for joint invasion, and that variation in OspC sequence contributes to strain-specific differences in tissue tropism displayed among Lyme disease spirochetes., Competing Interests: The authors have declared that no competing interests exist.

Synovial fluid samples represent only a very small percentage of routine work in a cytology laboratory. However, its microscopic examination allows us to observe different types of cells, particles and structures that, due to their morphological characteristics, may provide relevant data for cytodiagnosis. We present certain aspects related to arthrocentesis, the relationship between the gross appearance of synovial fluid and certain pathological processes, as well as the different techniques for processing and staining the smears. Furthermore, we describe the main cytological findings in various pathological conditions of the synovial joints, such as infections (bacterial and fungal), non-infectious inflammatory type (osteoarthrosis, rheumatoid arthritis, connective tissue diseases) and tumoral, distinguishing between primary and metastatic, both solid and haematological neoplasms., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: This study evaluated the incidence, risk factors, and clinical characteristics of complications of candidaemia in adults, with a focus on endophthalmitis, endocarditis, and osteoarticular infections., Methods: All patients ≥18 years old with candidaemia in two Korean tertiary hospitals from 2007 to 2016 were investigated. Complications of candidaemia were defined as the presence of endophthalmitis, endocarditis, or osteoarticular infections documented in patients with candidaemia. The clinical characteristics and risk factors for candidaemia with complications were analysed in the patients who underwent ophthalmological examinations., Results: Of 765 adult patients with candidaemia, 34 (4.4%) met the definition of complications, including endophthalmitis in 29 (3.8%), endocarditis in 4 (0.5%), and osteoarticular infections in 3 (0.4%). Of the 225 patients who underwent ophthalmological examinations, 29 (12.9%) had endophthalmitis. Candida albicans was an independent risk factor for complicated candidaemia (OR, 5.12; 95% CI, 2.17-12.09; P < 0.001). Although the mortality rate was no higher in complicated candidaemia, the duration of antifungal therapy was longer (23.1 ± 17.6 vs. 16.4 ± 10.8 days, P = 0.042), and 13 patients (39.3%) underwent additional procedures or surgery., Conclusions: Complications of candidaemia occurred in 4.4% of adult patients. C. albicans was an independent risk factor for complicated candidaemia in adults. Complications of candidaemia might need prolonged treatment and additional procedures or surgery. Therefore, careful evaluation and active treatment of candidaemia with complications should be encouraged., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We aimed to describe the use of subcutaneous teicoplanin as an alternative for the treatment of staphylococcal bone and joint infections., Methods: A retrospective multicentric cohort (2002-2015) was conducted with patients receiving subcutaneous teicoplanin for a staphylococcal bone and joint infection., Results: Forty patients were assessed. A median loading dose of 9.4 mg/kg/12h (IQR, 6.1-13.1) was administered to 35 patients, subcutaneously for 18 of them. Thirteen of these patients received three injections per week. No excess risk of failure was identified. The trough level was not significantly different between the various routes (p=0.462), and was significantly higher if the loading dose was≥9 mg/kg/injection (p<10 -3 )., Conclusion: The use of subcutaneous teicoplanin seems to be acceptable as an alternative to other routes of administration for antibiotics., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Community acquired-methicillin resistant Staphylococcus aureus (MRSA) clones, including ST1, ST8, and ST30 are reported worldwide. However, data among Korean children are limited. Thus, we investigated the molecular characteristics of S. aureus among children in Korea., Methods: S. aureus isolated from Korean children diagnosed with skin and soft tissue infection (SSTI) or bone and joint infection due to S. aureus infection at Seoul National University Bundang Hospital, from August 2010 to November 2016, were analyzed for multilocus sequence type (ST) and SCC mec typing. Polymerase chain reaction of Panton-Valentine leukocidin (PVL), qac A/B, smr and mupA genes were also performed. Electronic medical records were reviewed for clinical data and antibiotic susceptibility results. Cases were classified into three groups: health care-associated community-onset (HACO) infections, hospital-onset (HO) infections, and community-acquired (CA) infections., Results: A total of 67 strains from children with SSTI (41/67, 61.2%) and bone and joint infection (26/67, 38.8%) were included. Among all isolates, 29.9% (20/67) were MRSA, and 70% (14/20) were classified as CA, 20% (4/20) as HACO and 10% (2/20) as HO infections. MRSA rate according to disease was 34.1% (14/41) for SSTI and 23.1% (6/26) for bone and joint infection. MRSA strains included ST72-SCC mec IV (14/20, 70.0%), ST5-SCC mec II (3/20, 15.0%) and ST1-SCC mec IV (2/20, 10.0%). ST30 was the most common cause of SSTI and bone and joint infections and 96.6% (28/29) were methicillin-susceptible Staphylococcus aureus (MSSA). PVL genes were detected in 3 strains (3.8%, ST30-SCC mec IV n = 1, MSSA ST30 n = 2), qac A/B in 3 (MRSA = 3), smr in 3 (MSSA = 1, MRSA = 2) and mupA in 7 (MRSA = 5, MSSA = 2)., Conclusion: Molecular epidemiology of S. aureus in Korean children with SSTI and bone and joint infection showed that ST30 was predominant and mostly MSSA. Among MRSA, ST72-SCC mec type IV was the most common strain., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

We report here the case of a Prosthetic Joint Infection (PJI) associated with Coxiella burnetii in a 62-year-old man with a revised total hip arthroplasty. The diagnosis was performed first by 16S rDNA sequencing on hip fluid aspirate, and confirmed by specific qPCR. Q fever has been reported in few cases of Prosthetic Joint Infections, often associated with chronic evolution and iterative surgeries. This case report alerts about such an unexpected diagnosis in a patient with no known risk factors., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to describe clinical and diagnostic findings in cats with bone and joint disease associated with histoplasmosis., Methods: Medical records from between 2011 and 2017 were reviewed. Inclusion criteria required: (1) diagnosis of histoplasmosis by cytology, histology, urine or serum Histoplasma antigen testing, or culture; and (2) lameness or joint effusion as a presenting complaint or physical examination finding., Results: Twenty-five cases met the inclusion criteria. Four had incomplete records, but available data were included when applicable. Lameness was a presenting complaint in 17/21 cats and was the only complaint in 9/21 cats. Initial diagnosis was made by cytology in 22/25 cats and by culture, urine antigen and necropsy in one case each. Diagnostic cytology samples included synovial fluid (n = 13), lymph node (n = 5), skin (n = 2), lung (n = 1) and bone (n = 1). Two additional cases had synovial fluid examined but no organisms present. Inflammation was present in all synovial fluid samples examined. Biopsy was obtained in two cats and histologic diagnoses included osteomyelitis with no infectious organisms identified and severe lymphoplasmacytic synovitis suggestive of feline periosteal proliferative polyarthritis. Histoplasma urine antigen test was positive in 7/12 cats., Conclusions and Relevance: Inflammatory arthritis is common in cats with histoplasmosis, with lameness a common presenting complaint. Organisms are found in synovial fluid cytology in most cases. If not, appropriate additional diagnostics must be pursued.

Introduction. Prosthetic joint infections (PJIs) are challenging to treat therapeutically because the infectious agents often are resistant to antibiotics and capable of abundant growth in surface-attached biofilms. Though infection rates are low, ca. 1-2 %, the overall increase in the sheer number of joint replacement surgeries results in an increase in patients at risk. Aims. This study investigates the consensus of microbial species comprising PJI ecology, which is currently lacking. Methodology. In this study, PJI populations from seven patients were analysed using combined culturing and whole-genome shotgun sequencing (WGSS) to establish population profiles and compare WGSS and culture methods for detection and identification of the PJI microbiome. Results. WGSS detected strains when culture did not, notably dormant, culture-resistant and rare microbes. The CosmosID algorithm was used to predict micro-organisms present in the PJI and discriminate contaminants. However, culturing indicated the presence of microbes falling below the WGSS algorithm threshold. In these instances, microbes cultured are believed to be minor species. The two strategies were combined to build a population profile. Conclusions. Variability between and among PJIs showed that most infections were distinct and unique. Comparative analysis of populations revealed PJIs to form clusters that were related to, but separate from, vaginal, skin and gut microbiomes. Fungi and protists were detected by WGSS, but the role of fungi is just beginning to be understood and for protists it is unknown. These micro-organisms and their novel and strain-specific microbial interactions remain to be determined in current clinical tests.

Background: The optimal treatment of streptococcal prosthetic joint infections (PJIs) is unclear., Methods: A cohort of streptococcal PJIs was reviewed retrospectively in seven reference centers for the management of complex bone and joint infections, covering the period January 1, 2010 to December 31, 2012., Results: Seventy patients with monomicrobial infections were included: 47 had infections of total hip arthroplasty and 23 had infections of total knee arthroplasty. The median age was 77 years (interquartile range (IQR) 69-83 years), the median Charlson comorbidity score was 4 (IQR 3-6), and 15.6% (n=11) had diabetes. The most commonly identified streptococcal species were Streptococcus agalactiae and Streptococcus dysgalactiae (38.6% (n=27) and 17.1% (n=12), respectively). Debridement, antibiotics and implant retention (DAIR) was performed after a median time of 7 days (IQR 3-8 days), with polyethylene exchange (PE) in 21% of cases. After a minimum follow-up of 2 years, 27% of patients had relapsed, corresponding to 51.4% of DAIR treatment cases and 0% of one-stage (n=15) or two-stage (n=17) exchange strategy cases. Rifampicin or levofloxacin in combination therapy was not associated with a better outcome (adjusted p= 0.99). S. agalactiae species and DAIR treatment were associated with a higher risk of failure. On multivariate analysis, only DAIR treatment and S. agalactiae were independent factors of relapse. Compared to DAIR without PE, DAIR with PE was only associated with a trend towards a benefit (odds ratio 0.33, 95% confidence interval 0.06-1.96; adjusted p= 0.44)., Conclusions: Streptococcal PJIs managed with DAIR have a poor prognosis and S. agalactiae seems to be an independent factor of treatment failure., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes., Objective: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection., Design: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%., Setting: Twenty-six NHS hospitals., Participants: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively)., Interventions: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm., Main Outcome Measure: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data., Results: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial., Limitations: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded., Conclusions: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy., Future Work: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics., Trial Registration: Current Controlled Trials ISRCTN91566927., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 38. See the NIHR Journals Library website for further project information., Competing Interests: Adrian Taylor reports personal fees from Zimmer Inc., Corin Group and DePuy Synthes Companies outside the submitted work. Martin McNally reports personal fees from Bonesupport AB outside the submitted work. R Andrew Seaton reports personal fees from previous consultancy and funding for speaking at educational meetings (Novartis Pharma) and consultancy for Merck Sharp & Dohme Corp. (MSD) outside the submitted work. Harriet Hughes reports other competing interests from Gilead Sciences Inc., MSD, Biocomposites, and personal fees from Biocomposites and Cubist Pharmaceuticals outside the submitted work. Jennifer Bostock was a member of the Health Services and Delivery Research Commissioned Panel Members during this project.

Aims: Evaluation of 16S PCR in addition to the standard culture to improve the pathogen detection rate in clinical specimens., Methods and Results: Microbiological culture and direct 16S PCR was performed on specimens from suspected prosthetic joint infection patients (cohort-1) and on tissues and fluids from other normally sterile body sites (cohort-2). Based on clinical and microbiological data, the detection rate for both methods was assessed, assuming no superiority of either 16S PCR or culture. In cohort-1, 469 specimens were obtained. Culture was positive in 170 (36·2%) specimens, 16S PCR detected 70 (41·2%) of those pathogens. Additionally, 16S PCR detected pathogens in 13 of 299 (4·3%) culture-negative specimens. In cohort-2, pathogens were cultured in 52 of 430 (12·1%) specimens and 16S PCR revealed those pathogens in 32 (61·5%) specimens. 16S PCR detected pathogens in 31 of 378 (8·2%) culture-negative specimens., Conclusions: Overall, the yield with 16S PCR was low. For cohort-1 16S PCR detected pathogens in 4·3% of culture-negative specimens, where this was 8·2% for cohort-2., Significance and Impact of the Study: Although direct 16S PCR cannot replace culture, it may offer a valuable additional diagnostic option for detection of difficult to culture micro-organisms in culture-negative clinical specimens., (© 2018 The Society for Applied Microbiology.)

Background: In a two-stage exchange protocol for prosthetic joint infection (PJI), bacteria surviving over the antibiotic-loaded cement spacers may cause the persistence of infection with renewed clinical symptoms following the surgery. Culture after sonication of removed prosthesis is more sensitive than conventional periprosthetic tissue culture for the microbiological diagnosis of PJI. The aim of this study was to assess whether sonication of the spacer at the time of the second-stage procedure may improve the diagnosis of persistent PJI., Methods: We evaluated by microbiological culture the sonication fluid from 222 cement spacers implanted in a two-stage exchange protocol in 157 patients affected by PJI. A mean of 1.3 (range, 1-4) spacer per patient was performed., Results: In 53 out of 222 spacers analyzed infection was confirmed according to the MSIS criteria. In 22 cases the infection was confirmed by both cultures on periprosthetic tissue and on sonication fluid from the spacers. In 23 cases persistent PJI was identified because of only cultures of periprosthetic tissue and 8 because of results obtained after spacer sonication. The sensitivity of periprosthetic tissue cultures was higher than that of cultures performed on sonication fluid (84.9% vs 56.6%, p < .001)., Conclusions: Even though sonication of cement spacers has performances inferior than those reported for prosthesis, it can be considered a complementary method to unravel persistent infection during a two-stage exchange protocol for PJI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Prosthetic joint infections (PJIs) are among the most serious complications in arthroplasty. A second-site PJI in patients with multiple prosthetic joints increases morbidity, with many requiring further revision procedures. We aimed to establish why some patients with multiple joints develop second-site infections., Methods: Our institution's arthroplasty database was reviewed from 2004 to 2017. All PJIs were identified, and all patients with more than one prosthetic joint in situ were included. We recorded risk factors, causative organisms, number of procedures and length of stay., Results: Forty-four patients meeting the criteria were identified. Four patients (9.1%) developed second-site infection. Eight patients (18.2%) developed re-infection of the primary PJI. Positive MRSA carrier status and PJI of a total knee replacement were associated with an increased risk of a second episode of infection. Patients who developed further infection had more frequent admission and longer lengths of stay than isolated PJIs., Discussion: Higher morbidity and use of hospital resources are associated with this cohort of patients. PJIs in total knee replacements and positive MRSA status are associated with higher rates of second infection. Identifying this vulnerable cohort of patients at an early stage is critical to ensure measures are taken to reduce the risks of further infection.

We assessed the value of conventional culture, vial culture, and broad-range PCR of the sonication fluid (SF), individually or in combinations, for the diagnosis of prosthetic joint infection (PJI). We studied 114 consecutive patients (median age:72.5 years, males: 28.07%) undergoing removal of a total knee or hip prosthesis. By non-microbiologic criteria, 87 patients had aseptic failure, and 27 PJI. All patients had periprosthetic tissue culture, sonication of prosthesis, and study of SF by conventional and vial culture, and PCR. Compared to tissue culture, each test was significantly more sensitive and less specific. If only one test was positive, the sensitivity was 88.46% and specificity 64.29%. If all three SF tests were positive, sensitivity, and NPV were decreasing (34.6% and 80.23%), but specificity and PPV were increasing up to 98.57% and 90.9%, respectively, outperforming tissue culture. A triple negative test practically excluded PJI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. While generally successful, failure resulting in revision surgery is reported to be between 1.9 - 4.9%. However, when not related to traumatic re-injury, failure mechanism is poorly understood. One potential but understudied mechanism of ACL reconstruction failure is infection. We describe three patients with previous ACL reconstructions who later developed infection with Propionibacterium acnes. Two cases presented with knee pain and swelling, and one presented with instability. While only two of the three cases received antibiotic treatment, all three cases were free of knee and infectious symptomatology at most recent follow-up. P. acnes infection may represent one potential mechanism for biologic failure of ACL reconstruction and anaerobic operative cultures may be used to identify its presence.

Background: Prosthetic joint infection (PJI) is a severe complication of orthopaedic surgery. Preoperative diagnosis, although sometimes difficult, is key to choose the relevant treatment., Methods: We conducted a prospective study aimed at evaluating the diagnostic performance of a multiplex serological test for the pre-operative diagnosis of PJI. Blood samples were collected between 1 July 2016 and 31 July 2017 among patients referred for suspected PJI that occurred at least six weeks prior. Infection diagnosis was confirmed using intraoperative bacteriological cultures during prosthetic exchange., Results: Seventy-one patients were included, with a median age of 73 years (interquartile range [IQR]: 66-81) and 40 (56%) were male. Twenty-six patients had aseptic loosening and 45 patients had PJI. Among the latter, median time since the last surgery was 96 weeks (IQR: 20-324). Intraoperative cultures found Staphylococcus spp, Streptococcus spp or both in 39, 5 and 1 patients, respectively. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 81.8, 95.4, 97.3 and 72.4%, respectively, for all patients and 87.5, 93.5, 94.6 and 85.3%, respectively, for staphylococcal infections. Patients with false negative (FN) results had a significantly lower blood lymphocyte count (p = .045)., Conclusions: Multiplex serological test performed well among patients with chronic staphylococcal prosthetic infection. This approach could contribute to PJI diagnosis especially in patients for whom the pre-operative analysis of joint fluid is not informative.

Background: Hemolysis has been suggested as a feature conferring increased pathogenicity to certain Propionibacterium acnes strains in the setting of shoulder infection. The purpose of this study was to compare the virulence of hemolytic and nonhemolytic P acnes strains in patients undergoing revision shoulder arthroplasty., Methods: Thirty-nine patients with at least 1 positive culture growth for P acnes at the time of revision surgery were identified with P acnes isolates available for hemolysis testing. Patients were grouped into those with P acnes isolates positive (n = 20) and negative (n = 19) for hemolysis. The groups were retrospectively compared based on objective perioperative findings around the time of revision surgery and the postoperative clinical course, including the need for revision surgery. All cases were classified into categories of infection (definite infection, probable infection, and probable contaminant) based on objective perioperative criteria., Results: The presence of hemolysis was not significantly associated with an increased likelihood of infection (P = .968). Hemolysis demonstrated a 75% sensitivity and 26% specificity for determining infection (definite infection and probable infection categories). The hemolytic and nonhemolytic groups showed no difference regarding preoperative serum erythrocyte sedimentation rate and/or C-reactive protein level (P = .70), number of positive cultures (P = .395), time to positive culture (P = .302), and presence of positive frozen section findings (P = .501). Postoperatively, clindamycin resistance, shoulder function, and the rate of reoperation were not significantly different between the hemolytic and nonhemolytic groups., Conclusion: The presence of hemolysis was not associated with increased pathogenicity in patients with P acnes-positive cultures following revision shoulder arthroplasty, when assessed by objective perioperative criteria and the postoperative clinical course., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objectives: Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs., Methods: A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4× MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay., Results: Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC 50/90 , 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC 50/90 , 0.5/1μg/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC 50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h., Conclusions: This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

A rare case of clinical complication following a percutaneous coronary intervention is presented. A femoral vascular access was chosen to treat a coronary lesion with a stent implantation. This femoral vascular access, however, resulted in a pyogenic infection of the ipsilateral hip joint that was not properly diagnosed for an extended post-interventional period. The hip joint completely deteriorated before its underlying cause was identified. This case report illustrates the importance of recognizing potential endovascular complications independently of their frequency.

Background: Conventional local treatment for medullary osteomyelitis (OM) includes insertion of antibiotic-loaded polymethylmethacrylate (PMMA) cement. Nevertheless, PMMA may delivery irregular concentration of antibiotic to surrounding tissue. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded PMMA against multidrug resistant bacteria from OM isolates., Methods: We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2 mm), BAG-S53P4 granules (0.5-0.8 mm and < 45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0 mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 h of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test., Results: Inhibition of bacterial growth started soon after 48 h of incubation, reached zero CFU/ml between 120 and 168 h of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p < 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed., Conclusions: BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI.

Capnocytophaga canimorsus is a commensal organism commonly found in the oral cavity of cats and dogs. Infections with this organism are rare and can affect both immunocompetent and immunocompromised individuals. The authors present a case of C canimorsus causing indolent prosthetic hip joint infection in a healthy 66-year-old woman following a history of being scratched by her pet dog. The patient had an atypical history of chronic, low-grade infection which is unusual, as this organism is more frequently associated with acute presentations and fulminant sepsis. This patient was treated successfully with a two-stage exchange of her hip prosthesis and broad-spectrum antibiotics. C. canimorsus is a very rare cause of prosthetic joint infection but an important pathogen to consider, particularly in culture-negative joint infections and a history of animal exposure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Tubercular prosthetic joint infection (TB-PJI) is an uncommon complication. Lack of evidence of systemic tuberculosis and clinical suspicion could bring a delay in the time of the diagnosis. The aims of this study are to underline the importance of awareness and suspicion of mycobacterial infection in the differential diagnosis in PJI and to evaluate the appropriateness of different therapeutic options., Methods: Case report and literature review., Results: We report two cases of TB-PJI after total knee arthroplasty in Caucasian patients without prior history of tubercular disease or exposure. In both cases, the diagnosis was obtained years after the onset of symptoms. Despite that, both patients improved during antitubercular treatment (a four-drug regimen consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide for 2 months, followed by rifampicin and isoniazid). Moreover, after an 18-month course of treatment, there was no need for surgical therapy. The result of the literature review allows us to identify 64 cases of TB-PJI. Many differences in both medical and surgical management have been found, among those reviewed cases., Conclusions: Considering our experience and the literature review, we recommend considering a conservative approach (debridement and adequate antituberculous chemotherapy) as a suitable and safe option.

Fusobacterium nucleatum is an obligately anaerobic gram-negative rod, a component of the microbiome of the oropharynx and the gastrointestinal and urogenital tracts, causing an array of human infections which often include periodontal pathologies. As far as we know, there are no previous publications about acute periprosthetic joint infection due to Fusobacterium sp.; we report the first case in the medical literature of an aggressive, acute knee prosthetic infection due to F. nucleatum in a non-immunocompromised patient, unsuccessfully treated with a DAIR approach (Debridement + Antibiotics + Implant Retention)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed at describing the use of oral cyclines (i.e., doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients with periprosthetic joint infections (PJIs)., Methods: Medical charts of all patients with surgical revisions for PJIs who were given cycline-based SAT because of a high failure of various origins were reviewed. Data regarding tolerability and effectiveness of cycline-based SAT were analysed., Results: Seventy-eight patients of mean age 64 ± 17 years received cycline-base SAT in the period from January 2006 to January 2014. PJIs involved the knee in 37 patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2 (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were the most common pathogens accounting for 72.1% of the total number of bacterial strains identified. All included patients had surgery which consisted in debridement and implant retention in 59 of them (75.6%). Doxycycline and minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively. Adverse events were reported in 14 patients (18%), leading to SAT discontinuation in 6 of them (8%). After a mean follow-up of 1020 ± 597 days, a total of 22 (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition of tetracycline resistance in initial pathogen(s)., Conclusions: Our results suggest that oral cyclines used as SAT in patients treated for PJI have an acceptable tolerability and effectiveness and appear to be a reasonable option in this setting.

Background: Alpha defensin is a new biomarker that has been shown to have a very high accuracy to rule out periprosthetic joint infection. Recently, a new rapid lateral flow version of the alpha defensin test was developed and introduced to detect high levels of alpha defensin in synovial fluid quickly and with ease. We conducted a single-center prospective clinical study to compare the results of the Synovasure Alpha Defensin Test with those of the Musculoskeletal Infection Society (MSIS) criteria, which are considered to be the gold standard for diagnosing periprosthetic joint infection., Methods: A total of 223 consecutive patients with pain after total hip arthroplasty or total knee arthroplasty were enrolled into the study. In all patients, blood C-reactive protein was measured and joint aspirations were performed. From the synovial fluid, a leukocyte cell count with granulocyte percentage, microbiology cultures, and leukocyte esterase tests were carried out according to the recommendation of the MSIS for diagnosing periprosthetic joint infection. Concurrently, the Synovasure Alpha Defensin Test with a lateral flow device was performed from the aspirate. In the final clinical and statistical evaluation, 191 subjects with 195 joint aspirations (96 hips and 99 knees) were included. According to the MSIS criteria, there were 119 joints with an aseptic revision and 76 joints with periprosthetic joint infection., Results: After statistical analysis, the overall sensitivity of the Synovasure Alpha Defensin Test was 92.1% (95% confidence interval [CI], 83.6% to 97.1%), the specificity was 100% (95% CI, 97.0% to 100%), the positive predictive value was 100% (95% CI, 94.9% to 100%), and the negative predictive value was 95.2% (95% CI, 89.9% to 98.2%). The overall accuracy of the Synovasure test was 96.9% (95% CI, 93.4% to 98.9%), 189 of 195 cases., Conclusions: Our results suggest that the Synovasure periprosthetic joint infection test has a very high accuracy in diagnosing periprosthetic infections after total hip arthroplasty or total knee arthroplasty. Although the Synovasure Alpha Defensin Test does not provide information on the identity of the infectious pathogen, the test does have an important role in recognizing periprosthetic joint infection early and enables surgeons to start proper therapy without delay., Level of Evidence: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

This retrospective, case series describes our experience with the use of telavancin in patients with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and prosthetic joint infection. The primary objectives were clinical outcomes and adverse events (AEs), and a secondary outcome described microbiological susceptibility. Fourteen patients were enrolled. Median duration of therapy was 58 days, and four patients had concurrent bacteremia. End-of-treatment outcomes were available in 78% of patients, with a clinical success rate of 91%. Thirty-day and 12-month outcomes were also obtained. Seven patients experienced AEs. Infusion-related reactions were most common, and three AEs required discontinuation of therapy. All MRSA isolates had a telavancin MIC ≤0.06μg/ml, which is susceptible. This study indicates that telavancin may have a role in treatment of MRSA osteomyelitis and prosthetic joint infection. Our study describes clinical success and adverse events for long duration of therapy, up to 8 weeks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose of Review: Changes in the constituents and activity of the microbiome have been associated with a number of conditions linked to bone and joint disease. This review concentrates on ways in which the microbiome is known to influence osteoarthritis and osteoporosis., Recent Findings: Animal studies have demonstrated that changes in the microbiome can mediate the effects of obesity on cartilage degeneration. Additionally, the microbiome influences the amount of the bone (bone quantity), as well as bone tissue material properties (bone quality). Early clinical findings support the effects of the microbiome on osteoporosis and osteoarthritis. Although animal studies implicate the microbiome in the development of bone and joint disease, available results are limited and can be conflicting. Further investigation of the mechanisms linking from changes in the microbiome to alterations in the bones and joints are necessary.

Tedizolid, a second-generation oxazolidinone that displays a potent activity against Gram-positive pathogens, could be an interesting option for the treatment of bone and joint infections (BJIs). The aim of the study was to determine minimal inhibitory concentration (MIC) of tedizolid against a collection of 359 clinical isolates involved in clinically-documented BJIs and to compare them to those of comparator agents used in Gram-positive infections. Of the 104 Staphylococcusaureus and 102 coagulase-negative staphylococci (CoNS) isolates, 99 and 92 % were categorized as susceptible to tedizolid, respectively (MIC25=0.12/0.25 µg ml -1 and MIC90=0.25/0.5 µg ml -1 ), regardless of their methicillin resistance. MIC50 and MIC90 for the 51 enterococci, the 50 Corynebacterium spp. and the 52 Propionibacterium spp. were either equal or inferior to 0.5 µg ml -1 . Altogether, tedizolid possessed a potent in vitro activity against most of the BJI Gram-positive pathogens with 95 % of them exhibiting a MIC ≤0.5 µg ml -1 .