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An internal fixation composite structure of antibiotic cement plates was created. The aim of this study was to analyse the infection control effect of this structure when applied to treat a bone infection. We retrospectively analysed patients with bone infection admitted to our hospital between January 2013 and June 2019. After debridement, an antibiotic cement plate composite structure was used to fill and stabilize the defects. The treatment effect was evaluated at six months after surgery, and the infection control rate, factors associated with the recurrence of infection, and complications were analysed. If the patients had bone defects, the defect was repaired after infection control, and the infection control rate of all of the patients was re-evaluated at 12 months after surgery. A total of 548 patients were treated with this technique, including 418 men and 130 women. The infection sites included 309 tibias, 207 femurs, 16 radii and ulnae, 13 humeri, and 3 clavicles. After at least 6 months of follow-up, 92 patients (16.79%) had an infection recurrence and needed further treatment. The recurrence rate of the tibia was higher than that of the femur (P = 0.025). Eighty-nine out of 92 patients who relapsed underwent a second debridement with the same method, and the infection control rate after the second debridement was 94.71%. Complications included 8 cases of epidermal necrosis around the incision, 6 cases of internal fixation failure, and 30 cases of lower limb swelling. By the follow-up time of 12 months, another 6 patients had experienced recurrence of infection, and 4 cases were controlled after debridement. Finally, among all 548 cases, 7 patients remained persistently infected, and 6 underwent amputation. The infection control rate was 97.6% at the 1-year follow-up. The clinical efficacy of this new antibiotic cement plate composite structure for internal fixation after debridement of bone infection is stable and reliable.

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.

Septic nonunion is one of the major complications in fracture healing. The challenge is to identify the infection as the cause of nonunion first and then to achieve healing of the infection and the bone.Because of the more heterogeneous appearance of an infected nonunion, the prevalence of germ detection in surgical nonunion revision is often underestimated.In a retrospective study between 2010 and 2017, 86 patients with radiologically confirmed femoral shaft nonunion without clinical evidence and unremarkable medical history of a florid infection as the cause of nonunion, who had undergone primary single-stage surgical nonunion revision were analyzed. At least four intraoperatively obtained samples were evaluated for microbiological diagnosis. A distinction was made between tissue samples with subsequent 48‑h short-term incubation and tissue samples with 14-day long-term cultivation. The finding "germ detection" was made if at least two of the samples demonstrated bacterial growth.In 18 of 86 patients with a nonunion preoperatively judged to be aseptic, positive bacterial evidence was obtained after short-term incubation. After long-term cultivation, positive bacterial detection was possible in 38 of 86 patients with a femoral shaft nonunion initially classified as aseptic. Regarding potential risk factors, the two groups demonstrated no relevant differences. In 29 patients, 1 pathogen was isolated from the obtained samples, whereas in the remaining 9 patients, a mixed culture with an average of 2.9 ± 0.5 different bacteria was detected. Identification revealed mainly low-virulence bacteria, most commonly Staphylococcus epidermidis.If the preoperative diagnostics including clinical, laboratory and radiological examination as well as a careful anamnesis reveal indications of a possible infectious event, the surgical nonunion revision should be performed in two stages with specimen collection before definitive nonunion revision. For microbiological diagnosis, several representative tissue samples should independently be obtained from the nonunion site and incubated for 14 days. Only in the absence of evidence of septic nonunion is a single-stage procedure suggested.HINTERGRUND: Die infizierte Pseudarthrose stellt eine der schwerwiegendsten Komplikationen bei der Frakturheilung dar. Die Herausforderung besteht darin, die Infektion zuerst als Ursache einer Pseudarthrose zu erkennen und dann die Heilung der Infektion und des Knochens zu erreichen.Aufgrund des heterogeneren Erscheinungsbildes infizierter Pseudarthrosen wird die Prävalenz eines Keimnachweises bei der operativen Pseudarthrosenrevision häufig unterschätzt.In einer retrospektiven Untersuchung zwischen 2010 und 2017 wurden 86 Patienten, die aufgrund einer radiologisch gesicherten Femurschaftpseudarthrose primär revidiert wurden und die ohne klinische Hinweise auf einen floriden Infekt als Ursache der Pseudarthrose waren, analysiert. Es wurden mindestens 4 intraoperativ gewonnene Proben mikrobiologisch ausgewertet. Dabei wurde zwischen Gewebeproben mit anschließender 48-stündiger Kurzzeitbebrütung und Gewebeproben mit 14-tägiger Langzeitkultivierung unterschieden. Der Befund „Keimnachweis“ wurde gestellt, wenn mindestens 2 der Proben ein Keimwachstum zeigten.Bei 18 der 86 präoperativ als aseptisch eingeschätzten Pseudarthrosen konnte nach Kurzzeitbebrütung ein positiver Keimnachweis erhoben werden. Nach Langzeitbebrütung war bei 38 von 86 Patienten ein positiver Keimnachweis möglich. Hinsichtlich potenzieller Risikofaktoren zeigten die beiden Gruppen keine relevanten Unterschiede. Bei 29 Patienten wurde ein einzelner Erregertyp aus den gewonnenen Proben isoliert, während bei den übrigen 9 Patienten eine Mischkultur mit durchschnittlich 2,9 ± 0,5 verschiedenen Bakterien nachgewiesen wurde. Bei der Keimidentifizierung fanden sich mit Staphylococcus epidermidis am häufigsten niedrigvirulente Bakterien.Ergibt die präoperative Diagnostik unter Einbeziehung der klinischen, laborchemischen und radiologischen Untersuchung sowie der Anamnese Hinweise auf ein mögliches Infektgeschehen, sollte die operative Revision zweizeitig mit Probengewinnung vor der definitiven Pseudarthrosenrevision erfolgen. Zur mikrobiologischen Diagnostik sollten mehrere repräsentative Gewebeproben unabhängig voneinander aus der Pseudarthrosenzone gewonnen und für 14 Tage bebrütet werden. Nur bei fehlenden Hinweisen auf eine infizierte Pseudarthrose wird das einzeitige Vorgehen vorgeschlagen.

Objectives To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. Methods Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. Results Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5 g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. Conclusion Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.

Aim: This retrospective study’s objective was to evaluate osteoarticular infection in infants less than 12 months of age, with a particular focus on biological features and bacteriological etiology. Material & methods: We retrospectively reviewed the medical records of every infant younger than 12 months old admitted in our institution for a suspected osteoarticular infection between January 1980 and December 2016. Results: Sixty-nine patients records were reviewed, including eight neonates, 16 infants from 1 to 5 months old, and 45 from 6 to 12 months old. Conclusion: Neonates and infants aged from 6 to 12 months old were more exposed to infections. Staphylococcus aureus remained the main pathogen in children

Objectives We reported the impact of internal guidelines coupled with selective reporting of antibiotic susceptibility tests (srAST) on antibiotic adequacy in healthcare facilities. Methods This prospective study involved clinicians from three clinics with medical and surgical activities employing a full-time infectious disease (ID) specialist. Internal guidelines were updated in 2016. The clinics were working with the same laboratory, which delivered the srAST introduced in March 2017. Two weeks per month over a 6-month period, all isolated bacterial specimens, empirical antibiotic therapies (EAT) and the documented ones were analyzed. An EAT listed in the guidelines and a documented therapy mentioned in the srAST defined their adequacy. Results A total of 257 positive bacterial samples were analyzed in 199 patients, for which 106 infections were studied. Of these, 32% were urinary tract infections, 15% were primary bloodstream infections, 11% were bone infections, and 42% were other types of infection. The three main bacteria were Escherichia coli (27%), Staphylococcus aureus (24%), and Enterococcus faecalis (14%). The total number of antibiotic prescriptions was 168, with 75 (45%) EATs and 93 (55%) documented therapies. There were 35/75 (47%) adequate EATs and 86/93 (92%) adequate documented therapies. The ID specialist was not involved in 90/168 (53.5%) prescriptions, of which 43/90 (48%) were adequate, with 21/35 (60%) EATs and 22/86 (25%) documented therapies. There was a statistical correlation between compliance of the EATs with guidelines and of the documented therapy with srAST (p = 0.02). Conclusion Combining internal guidelines and srAST led to a high rate of antibiotic adequacy.

Objective To describe the clinical features of osteoarticular infection in infants cared for in neonatal intensive care units (NICUs) and to assess the presence of multifocal infection. Study design Retrospective medical record review with structured data abstraction of infants with osteomyelitis or pyogenic arthritis or both in NICUs at 3 children's hospitals over a 29-year period. Results Of the 45 cases identified, 87% occurred in prematurely born infants, with a median gestational age of 27.4 weeks (IQR, 26, 31 weeks). Median postnatal age at diagnosis of infection was 33 days (IQR, 20, 50 days). Osteomyelitis was present without joint involvement in 53% and with joint involvement in 44% of cases. Methicillin-susceptible Staphylococcus aureus (71%) was the predominant pathogen, despite prevalent methicillin-resistant S aureus in community-associated infections. More than 1 bone was infected in 34% of cases. The femur (in 50% of patients) was the most frequently involved bone and the hip (in 20% of patients) was the most frequently involved joint. Bacteremia persisted for 4 or more days in 54% of patients with a positive blood culture despite active antimicrobial therapy. Conclusions Among infants with osteoarticular infection in NICUs, multifocal disease is common and frequently is unsuspected. Search for additional sites of infection including the hip is warranted following the diagnosis of osteoarticular infection at a single site. Involvement of contiguous joints should be suspected in cases of osteomyelitis; conversely the presence of pyogenic arthritis usually indicates extant osteomyelitis in a contiguous bone.

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.

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. Keywords: Candidaemia, Complication, Candida albicans

Background The treatment for infected tibial bone defects can be a great challenge for the orthopaedic surgeon. This meta-analysis was conducted to compare the safety and efficacy between bone transport (BT) and the acute shortening technique (AST) in the treatment of infected tibial bone defects. Methods A literature survey was conducted by searching the PubMed, Web of Science, Cochrane Library, and Embase databases together with the China National Knowledge Infrastructure (CNKI) and the Wanfang database for articles published up to 9 August 2019. The modified Newcastle-Ottawa scale (NOS) was adapted to evaluate the bias and risks in each eligible study. The data of the external fixation index (EFI), bone grafting, bone and functional results, complications, bone union time and characteristics of participants were extracted. RevMan v.5.3 was used to perform relevant statistical analyses. Standard mean difference (SMD) was used for continuous variables and relative risk (RR) for the binary variables. All of the variables included its 95% confidence interval (CI). Results Five studies, including a total of 199 patients, were included in the study. Statistical significance was observed in the EFI (SMD = 0.63, 95% CI: 0.25, 1.01, P = 0.001) and bone grafting (RR = 0.26, 95%CI: 0.15, 0.46, P P = 0.92), bone results (RR = 0.97, 95% CI: 0.91, 1.04, P = 0.41), functional results (RR = 0.96, 95% CI: 0.86, 1.08, P = 0.50) and complications (RR = 0.76, 95% CI: 0.41, 1.39, P = 0.37). Conclusions AST is preferred from the aspect of minimising the treatment period, whereas BT is superior to AST for reducing bone grafting. Due to the limited number of trials, the meaning of this conclusion should be taken with caution for infected tibial bone defects.

We aimed to estimate the prevalence of Staphylococcus aureus producing Panton-Valentine leucocidin (PVL) isolated from children diagnosed with osteoarticular infections (OAIs), and to examine risk factors and clinical features.This prospective study was conducted from January 2017 to December 2018. All hospitalised children diagnosed with S. aureus OAI are included. Blood cultures, articular fluids, synovial tissues and/or bone fragments were collected for bacteriological culture. Antimicrobial susceptibility tests were determined by disk diffusion method. Genes encoding methicillin resistance (mecA) and PVL virulence factors (luk-S-PV and luk-F-PV) were detected by multiplex polymerase chain reaction. The demographic, clinical, laboratory, radiographic and clinical features were reviewed prospectively from medical records.A total of 37 children with S. aureus OAIs were included, 46% of them have PVL-positive infection and 70.6% were male. The mean age was 8.12 years (±4.57), and almost were from rural settings (76.5%). Children with Staphylococcus aureus producing Panton-Valentine leucocidin (SA-PVL) were significantly associated with type of infection (P = 0.005), location of infection (P = 0.037) and abnormal X-ray (P = 0.029). All strains SA-PVL+ are sensitive to methicillin, but one strain SA-PVL negative was methicillin-resistant S. aureus, confirmed by gene mecA positive.The prevalence of S. aureus infections producing PVL toxin was high in OAIs amongst Moroccan children, mainly due to methicillin-susceptible S. aureus. Type and location of infections and abnormal X-ray were significantly associated with SA-PVL. Routine diagnostic testing of PVL-SA, continuous epidemiological surveillance and multidisciplinary management of OAI is essential to prevent serious complications.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against

International audience; Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R(2) adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being “GMP-like”) targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally “phage therapy 2.0” has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial–academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

BackgroundThe progress of diagnostic strategies and molecular methods improved the detection ofKingella kingaein bone and joint infections, and now,Kingella kingaeis 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 ofKingella Kingaein negative culture bone and joint pediatric infections, and to describe the clinical and biologic features of these children.MethodsFrom 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 researchingK. kingaespecific genecpn60. Microbial culture and identification were made using standard bacteriological methods. The demographics, clinical, laboratory, radiographic and clinical features were reviewed from medical records.ResultsWe enrolled 65 children with culture negative BJI, 46 of them having under 10 years old have been screened for thecpn60gene. Thus, the gene encodingKingella kingaewas 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..ConclusionK kingaeis 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 specificK. kingaePCR assay can provide a better diagnostic performance of BJI.

INTRODUCTION: Osteomyelitis is an increasing burden on the society especially due to the emergence of multiple drug-resistant organisms. The lack of a central registry that prospectively collects data on patient risk factors, laboratory test results, treatment modalities, serological analysis results, and outcomes has hampered the research effort that could have improved and provided guidelines for treatments of bone infections. The current manuscript describes the lessons learned in setting up a multi-continent registry. MATERIALS AND METHODS: This multicenter, international registry was conducted to prospectively collect essential patient, clinical, and surgical data with a 1-year follow-up period. Patients 18 years or older with confirmed S. aureus long bone infection through fracture fixation or arthroplasty who consented to participate in the study were included. The outcomes using the Short Form 36 Health Survey Questionnaire (version 2), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at baseline and at 1 month, 6 months, and 12 months. Serological samples were collected at follow-ups. RESULTS: Contract negotiation with a large number of study sites was difficult; obtaining ethics approvals were time-consuming but straightforward. The initial patient recruitment was slow, leading to a reduction of target patient number from 400 to 300 and extension of enrollment period. Finally, 292 eligible patients were recruited by 18 study sites (in 10 countries of 4 continents, Asia, North and South America, and Central Europe). Logistical and language barriers were overcome by employing courier service and local monitoring personnel. CONCLUSIONS: Multicenter registry is useful for collecting a large number of cases for analysis. A well-defined data collection practice is important for data quality but challenging to coordinate with the large number of study sites.

Increased use of implantable biomedical devices demonstrates their potential in treating a wide variety of ailments and disorders in bone trauma and orthopaedic, reconstructive, and craniofacial applications. However, the number of cases involving implant failure or malfunction due to bacterial infection have also increased in recent years. Implanted devices can facilitate the growth of bacteria as these micro-organisms have the potential to adhere to the implant and grow and develop to form biofilms. In an effort to better understand and mitigate these occurrences, biomaterials containing antimicrobial agents that can be released or presented within the local microenvironment have become an important area of research. In this review, we discuss critical factors that regulate antimicrobial therapy to sites of bone infection, such as key biomolecular considerations and platforms for delivery, as well as current in vivo models and current advances in the field. STATEMENT OF SIGNIFICANCE: This review outlines the important factors that are taken into consideration for the development of biomaterials for local delivery of therapeutics to the site of bone infections. An overview of important criteria for development of this model (such as type of bone defect, antimicrobial therapeutic, and delivery vehicle) are provided, along with current research that utilizes these considerations. Additionally, this review highlights recent clinical trials that have utilized antimicrobial therapeutics for treatment of osteomyelitis.

Recommendation:Transfer of synovial aspirate in blood culture bottles, obtaining deep biopsy of tissues and bone, obtaining multiple samples, increasing incubation period of cultures, and the use of molecular techniques for culture negative cases are some of the strategies that can help improve the ability to isolate the causative organism(s) in infections of foot and ankle.Level of Evidence:Moderate.Delegate Vote:Agree: 100%, Disagree: 0%, Abstain: 0% (Unanimous, Strongest Consensus)

Corynebacterium striatum is a ubiquitous colonizer of human skin and mucous membranes. It is increasingly involved in infections, especially with prosthetic devices or in immunocompromised individuals. Microbiological diagnosis is challenging and bacterial resistance is a major concern. We performed a retrospective study of monomicrobial bone and joint infections (BJI) due to C. striatum in two referral centers from April 2012 to July 2017. We collected the patients' clinical and microbiological characteristics and outcomes. We also performed a literature review of BJI due to C. striatum. We identified 12 cases (nine prosthetic joint infections, one osteosynthetic device infection, one non-union, and one arthritis) in 11 patients, five of which were immunocompromised. Microbiological diagnosis was performed with prolonged culture media. Ten out of 12 strains were susceptible to aminopenicillin, a drug class not recommended for testing by the EUCAST/CASFM guidelines, and 8/12 patients were treated with amoxicillin-rifampicin. The cure rate was 8/12, after a median follow-up period of 487.5 days (IQR 140.3-1348.5). Twelve cases of BJI due to C. striatum were previously reported. Among them, 5/12 patients were immunocompromised, 3/12 cases were acute BJI, and 2/12 were device-related infections. The diagnosis was performed by PCR in one case, and 10/12 patients were treated with glycolipopeptides, with a cure rate of 11/12. We report the largest cohort of monomicrobial BJI with C. striatum. Determination of aminopenicillin susceptibility is essential since it is frequently active in our experience, even in BJI. The cure rate of this infection seems high.

Background: Sphingomonas paucimobilis is an emerging opportunistic bacterium with a particular tropism toward bones and soft tissues. It is a gram-negative rod that can infect immunosuppressed or immunocompetent individuals in the community or hospital settings. Prognosis of infected patients is generally good, but morbidity and mortality cases have both been documented. Objectives: To present and discuss all reported Sphingomonas paucimobilis-mediated bone and soft-tissue infections, and shed light upon the relevance of this organism in orthopaedic surgery. Data sources: Pubmed and Cochrane Library. Study eligibility criteria: Studies reporting at least one human bone or soft-tissue infection due to Sphingomonas paucimobilis. Results: Ten articles describing 19 patients met the inclusion criteria. Common infections included osteomyelitis, cellulitis, and septic arthritis. Fifteen patients (78.9%) had community-acquired diseases. All patients were successfully treated with antibiotic therapy and only one (5.3%) had a residual complication. Limitations: The study included a small sample size presenting with bone or soft-tissue infections. Some cases had lacking data. Conclusion: Despite being associated with a good prognosis in most cases, Sphingomonas paucimobilis-related orthopaedic infections may exhibit some complications. Keywords: Sphingomonas paucimobilis, Bone, Soft tissue, Infections

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.

The presence of methicillin-resistant

We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused byThe medical charts of all children presenting with OAIs to our institution over a 13-year period (January 2007 to December 2019) were reviewed. Among these patients, we extracted those which presented an OAI caused by

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244.

Background. The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of infected nonunion of tibia and to perform meta-analysis of bone results and infection recurrence to assess the efficacy of an antibiotic spacer combined with Ilizarov methods. Methods. The MEDLINE, Embase, Cochrane Library, CNKI, and CBM (Chinese Biological Medicine) databases were searched for articles published between January 2000 and July 2020. Assessment of study quality was performed using a modified version of the Newcastle-Ottawa scale. Effect size and 95% confidence intervals were calculated for the main outcome. Heterogeneity was assessed. Fixed-effect modeling and Stata version 15.1 were used to analyze the data. Sensitivity analyses were conducted with the evidence of heterogeneity. Results. 11 studies involving 210 patients with infected nonunion of tibia were finally included in our meta-analysis. Bone results and infection recurrence were analyzed based on the single-arm meta-analysis. The average of external fixation index (EFI) was 46.88 days/cm in all studies included. The excellent rate in bone results and the rate of infection recurrence was 65% (95% CI: [0.22, 0.97], I 2 = 0.0 % , P = 0.932 ) and 6.99% (95% CI: [0.052, 0.325], I 2 = 0.0 % , P = 1.000 ) in patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods. Conclusions. Our meta-analysis revealed that the patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods had a high rate of excellent bone results and a low rate of infection recurrence. Therefore, combining the antibiotic spacer with Ilizarov methods may be an applicable choice for repairing and reconstructing infected nonunion of tibia.

Background Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. Methods This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. Results Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. Conclusions Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.