Proportion of patients with prosthetic joint infection eligible for adjuvant phage therapy: a French single-centre retrospective study.

BACKGROUND: Bone and joint infections represent a major public health issue due to their increasing prevalence, their functional prognosis and their cost to society. Phage therapy has valuable anti-biofilm properties against prosthetic joint infections (PJI). The aim of this study was to establish the proportion of patients eligible for phage therapy and to assess their clinical outcome judged against all patients presenting with PJI. METHOD: . Patients admitted for periprosthetic joint infection (PJI) at a French general hospital between 2015 and 2019 were retrospectively included. Eligibility for phage therapy was determined based on French recommendations, with polymicrobial infections serving as exclusion criteria. Patients were categorized into two groups: those eligible and those ineligible for phage therapy. We analyzed their characteristics and outcomes, including severe adverse events, duration of intravenous antibiotic therapy, length of hospitalization, and relapse rates. RESULTS: . In this study, 96 patients with PJI were considered in multidisciplinary medical meetings. Of these, 44% patients (42/96) were eligible for additional phage therapy. This group of patients had a longer duration of intravenous therapy (17 days vs. 10 days, p = 0.02), more severe adverse events (11 vs. 3, p = 0.08) and had a longer hospital stay (43 days vs. 18 days, p < 0.01). CONCLUSION: . A large number of patients met eligibility criteria for phage therapy and treatment and follow-up is more complex. A larger epidemiological study would more accurately describe the prognosis of eligible patients.

Clinical and molecular characteristics of methicillin-resistant Staphylococcus aureus in bone and joint infection among children.

OBJECTIVE: To investigate the characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in bone and joint infection (BJI) among children. METHODS: A total of 338 patients diagnosed with BJI from 2013 to 2022 in Children's Hospital of Fudan University were enrolled. Demographic information, microbiology culture results and laboratory findings, including white blood counts (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) were collected and analyzed. MRSA was confirmed by antimicrobial susceptibility testing. Other MRSA-caused infections were randomly selected for comparison. Twenty-three virulence and antimicrobial resistance (AMR) genes were screened for MRSA strains. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing were performed using PCR amplification and sequencing. RESULTS: Of the identified pathogens in BJI, MRSA accounted for 21.0% (47/224). Patients with BJI had high levels of initial CRP, white blood cell count (WBC) and IL-6. ST59 (43.9%) and t437 (37.6%) were the main MRSA subtypes isolated from the children. The major genotypes in BJI were ST59-t437 (29.8%) and ST22-t309 (14.9%), with high carriage of hemolysins including hla (94.4-100%), hlb (66.2-93.3%), and hld (100%). Notably, Panton-Valentine leukocidin (pvl) had a high prevalence (53.3%) in ST22-t309-MRSA. Other virulence genes including tst, seg and sei were more commonly detected in ST22-t309-MRSA (40.0-46.7%) than in ST59-t437-MRSA (4.2-9.9%). High-carriage AMR genes in MRSA included aph(3')/III (66.7-80%), ermB (57.5-73.3%) and ermC (66.7-78.9%). MRSA presented high-resistance to erythromycin (52.0-100%) and clindamycin (48.0-92.5%), different genotypes displayed variation in their susceptibilities to antibiotics. CONCLUSIONS: The major MRSA genotype in BJI was ST59-t437, followed by ST22-t309, with a higher prevalence of the pvl gene. Continuous surveillance of pvl-positive ST22-t309-MRSA in pediatric BJI infections is thus required.

Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients.

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.

Enhancing Diagnostics in Orthopedic Infections.

Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.

Are Cutibacterium acnes present at the end of primary shoulder prosthetic surgeries responsible for infection? Prospective study.

The purpose of this study was to investigate if the C. acnes present at the end of a primary shoulder arthroplasty could be responsible for shoulder arthroplasty infection. Prospective study includes patients undergoing primary shoulder arthroplasty from January 2015 until December 2018. From all the patients included, 5 to 12 tissue samples were obtained and were specifically cultured to detect the presence of C. acnes. DNA was extracted from the C acnes isolated colonies and Whole Genome Sequencing (WGS) analysis was done. A cohort of 156 patients was finally included. In twenty-seven patients, the C. acnes was present at the end of the primary surgery. Two of these patients developed a C. acnes periprosthetic shoulder infection at 6 and 4 months after the primary surgery. WGS of C. acnes isolated colonies showed that all the revision-surgery isolates clustered near to the corresponding primary-surgery isolates compared to the other independent bacterial colonies. (99.89% of similarity). C. acnes present at the end of the primary surgery can be the cause of early or delayed periprosthetic joint infections in shoulder arthroplasty.

Global epidemiology of childhood bone and joint infection: a systematic review.

PURPOSE: Childhood bone and joint infection (BJI) is a potentially severe disease that may have permanent sequelae, including growth impairment and limb deformity. It has been characterised in the literature with a focus on Western epidemiology; there are currently no reports detailing global epidemiology and bacteriology. This omits key data from determining temporal trends, appropriate antibiotic therapy, and resource allocation. This review aims to identify studies that characterise the incidence of childhood bone and joint infection or provide detailed bacteriology within their region. METHODS: A systematic review of the literature was performed from 01/01/1980 to 31/12/2020. Data has been analysed to give incidence of disease per 100,000 children, primary pathogen by country where available, and risk ratio (RR) for disease by ethnicity. This is applicable for areas that experience race-related inequitable burden of disease. RESULTS: Forty-four articles met the inclusion area; of these, seven were population-wide studies, primarily from Europe or the United States, and the remainder were cohort studies. Incidence could be derived from 26 studies compromising over 34, 000 children. Information on bacteriology was available from 39 publications (10, 957 cases). Methicillin-sensitive Staphylococcus aureus is the most common pathogen in the West. Recently, disease secondary to Kingella kingae and methicillin-resistant S. aureus has increased. Salmonella remains a dominant pathogen in African regions. Increased risk of disease is observed in Aboriginal, New Zealand Maori, Pacific, Indigenous Fijian, and Bedouin children. CONCLUSION: The current state of the literature detailing incidence of childhood BJI focuses on disease patterns from the West. There is a paucity of high-quality publications in the developing world. Despite these limitations, global trends in burden of disease show race-related inequitable risk of BJI. Temporal and regional variation in bacteriology can be demonstrated. LEVEL OF EVIDENCE: III.

Establishment of an interdisciplinary board for bone and joint infections.

PURPOSE: The incidence of bone and joint infections is increasing while their treatment remains a challenge. Although guidelines and recommendations exist, evidence is often lacking and treatment complicated by complex clinical presentations and therapeutic options. Interdisciplinary boards shown to improve management of other diseases, seem potentially helpful. We describe the establishment of an osteomyelitis board to show the existing demand for such a platform. METHODS: All patients discussed in the board for bone and joint infections between October 2014 and September 2020 were included in this retrospective study. Data were extracted from patient records and analyzed descriptively. RESULTS: A total of 851 requests related to 563 patients were discussed in the board during the study period. After a run-in period of 3 years, a stable number of cases (> 170/year) were discussed, submitted by nearly all hospital departments (22 of 25). Recommendations were mainly related to antibiotic treatment (43%) and to diagnostics (24%). Periprosthetic joint infections were the most frequent entity (33%), followed by native vertebral osteomyelitis and other osteomyelitis. In 3% of requests, suspected infection could be excluded, in 7% further diagnostics were recommended to confirm or rule out infection. CONCLUSIONS: A multidisciplinary board for bone and joint infections was successfully established, potentially serving as a template for further boards. Recommendations were mainly related to antibiotic treatment and further diagnostics, highlighting the need for interdisciplinary discussion to individualize and optimize treatment plans based on guidelines. Further research in needed to evaluate impact on morbidity, mortality and costs.

First report of Kingella kingae diagnosed in pediatric bone and joint infections in Morocco.

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.

Ten-year retrospective review of paediatric septic arthritis in a New Zealand centre.

BACKGROUND: Paediatric septic arthritis, although a rare diagnosis in the developed world, remains a significant challenge in the New Zealand population. In recent years, there has been effort to characterize the nature of paediatric bone and joint infection for New Zealand due to rising incidence of osteomyelitis and staphylococcal sepsis [1, 2]. We have sought to identify trends in presentation, diagnosis and management of paediatric septic arthritis, with added focus on ethnicity and access to healthcare. METHODS: A ten year retrospective review of all cases < 16 years with presumed septic arthritis presenting to a tertiary referral centre between 2008 and 2018 was performed. RESULTS: A total of 103 cases met inclusion criteria. Mean age was 5.9 years (SD +/- 4.17) with a male predominance (64%). Traditional laboratory culture method isolated an organism in 66% of cases: Staphylococcus aureus was the most common pathogen identified (61%). Incidence varied greatly by ethnicity 1:16,000 for NZ European children; 1:8760 for Pacifica and 1:4300 for Maori. Mean distance travelled by patients to reach the nearest emergency department was 38.3 km, ranging from 2 to 188 km. Assessment using NZ deprivation scores showed the Maori paediatric population were likely to reside in areas of worse socioeconomic deprivation (p = 0.0005). The majority (66%) of cases were treated surgically with a low recurrence rate (2.9%). Delayed presentation was associated with worse outcomes and more likely in patients residing > 20 km away from the nearest emergency department. CONCLUSION: The incidence of paediatric septic arthritis in New Zealand is concerningly high within Maori and Pacific populations. Future health interventions should consider environmental, socioeconomic, and microbiological trends in the burden of disease.

Investigation of a Staphylococcus argenteus Strain Involved in a Chronic Prosthetic-Joint Infection.

Staphylococcus argenteus is an emerging species responsible for infections comparable to those induced by Staphylococcus aureus. It has been involved in few chronic or persistent infections so far. In this study, we described a case of a persistent prosthetic-joint infection (PJI) affecting a young woman. We investigated in vitro the virulence traits of the incriminated S. argenteus strain (bone cell invasion, biofilm formation and induction of inflammation) and analyzed its genome, in comparison with two other strains of S. argenteus and two S. aureus isolates. It appeared that this S. argenteus PJI strain combined biofilm formation, osteoblast invasion and intracellular persistence abilities together with genes potentially involved in the escape of the host immune defenses, which might explain the chronicization of the infection.

Multidisciplinary management of the bone and joint infection complicating treatment of an open fracture of the lower limb.

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.

Molecular Typing of Multiple Isolates Is Essential to Diagnose Cutibacterium acnes Orthopedic Device-related Infection.

Cutibacterium acnes orthopedic device-related infections (ODRIs) range from obvious infections to solely culture-based diagnoses. Multilocus sequence typing of multiple isolates from the same procedure revealed that most cases with normal C-reactive protein levels that were classified as C. acnes ODRI would be considered contaminations when accounting for genotypic data.

Monomicrobial bone and joint infection due to Corynebacterium striatum: literature review and amoxicillin-rifampin combination as treatment perspective.

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.

Peptoniphilus asaccharolyticus - Commensal, pathogen or synergist? Two case reports on invasive Peptoniphilus asaccharolyticus infection.

Peptoniphilus asaccharolyticus are gram-positive anaerobic cocci (GPAC) usually found as commensals of the skin or in the setting of polymicrobial colonisation of chronic wounds and ulcers. However, its pathogenic potential in more severe, invasive infections such as bone, joint or blood stream infections remains unclear, with studies on underlying virulence factors still pending. In this case report we present two cases of P. asaccharolyticus-associated infections of the bone and joint as well as a review of the literature. The cases cast a new light on possible synergistic interactions between P. asaccharolyticus and more virulent aerobic bacteria as well as on its role as pathogen in severe mono-infection.

Multidisciplinary team meeting for complex bone and joint infections diagnosis: The PHICTOS study.

BACKGROUND: In France, the most severe bone and joint infections (BJI), called "complex" (CBJI), are assessed in a multidisciplinary team meeting (MTM) in a reference center. However, the definition of CBJI, drawn up by the Health Ministry, is not consensual between physicians. The objective was to estimate the agreement for CBJI classification. METHODS: Initially, five experts from one MTM classified twice, one-month apart, 24 cases as non-BJI, simple BJI or CBJI, using the complete medical record. Secondly, six MTMs classified the same cases using standardized information. Agreements were estimated using Fleiss and Cohen kappa (κ) coefficients. RESULTS: Inter-expert agreement during one MTM was moderate (κ=0.49), and fair (κ=0.23) when the four non-BJIs were excluded. Intra-expert agreement was moderate (κ=0.50, range 0.27-0.90), not improved with experience. The overall inter-MTM agreement was moderate (κ=0.58), it was better between MTMs with professor (κ=0.65) than without (κ=0.51) and with longer median time per case (κ=0.60) than shorter (κ=0.47). When the four non-BJIs were excluded, the overall agreement decreased (κ=0.40). CONCLUSION: The first step confirmed the heterogeneity of CBJI classification between experts. The seemingly better inter-MTM than inter-expert agreement could be an argument in favour of MTMs, which are moreover a privileged place to enhance expertise. Further studies are needed to assess these results as well as the quality of care and medico-economic outcomes after a MTM.

[Kingella kingae bone and joint infections]. / Arthrites à Kingella kingae chez l'enfant : à propos de six cas.

We report six cases of children with probable or confirmed Kingella kingae bone and joint infections (BJI) and discuss the role of this pathogen in the pediatric population. The advent of Polymerase Chain Reaction (PCR) led to the recognition of the importance of Kingella kingae in several human diseases, particularly in BJI affecting children aged 6 to 48 months. Kingella kingae infections in children have most often a good prognosis provided that the diagnosis is discussed, appropriate diagnostic methods are performed and effective antibiotics are prescribed.

Nous rapportons 6 cas probables ou confirmés d'infections ostéoarticulaires (IOA) à Kingella kingae et proposons une revue de l'implication de ce pathogène en pédiatrie. L'avènement de la PCR (Polymerase Chain Reaction) a mis en lumière son rôle dans diverses maladies humaines, en particulier les IOA chez les enfants âgés de 6 à 48 mois. Le pronostic des infections à Kingella kingae chez l'enfant est le plus souvent bon, pour autant que le diagnostic soit évoqué, que les méthodes diagnostiques adéquates soient utilisées et qu'une antibiothérapie appropriée soit instaurée.

In-Host Adaptation of Salmonella enterica Serotype Dublin during Prosthetic Hip Joint Infection.

Genome degradation has been central to the adaptation of Salmonella enterica serotypes to their hosts throughout evolution. We witnessed the patho-adaptation of a strain of Salmonella Dublin (a cattle-adapted serotype) to a human host during the course of a recurrent prosthetic hip joint infection evolving over several years.

Community-Acquired Staphylococcus argenteus Sequence Type 2250 Bone and Joint Infection, France, 2017.

We report a rare case of Staphylococcus argenteus bone and joint infection in a 9-year-old boy in France. His finger arthritis was complicated by osteitis 5 weeks later, which resulted in a secondary intervention. This case indicates the virulence of S. argenteus, an emerging pathogen whose clinical effects are poorly described.

Case of femoral pseudarthrosis due to Scedosporium apiospermum in an immunocompetent patient with successful conservative treatment and review of literature.

Scedosporium apiospermum is a ubiquitous filamentous fungus, commonly found in soil, sewage and polluted waters. It is rarely pathogenic but can cause a broad spectrum of clinical diseases, which can be localised or disseminate to distant organs. The disseminated form of the disease is mostly seen among immunocompromised patients. However, some rare cases of disseminated disease have been reported in immunocompetent individuals. Treatment of these infections is challenging because of their natural resistance to many antifungal agents. Here, we report the case of a 57-year-old immunocompetent patient diagnosed with femoral pseudarthrosis due to S. apiospermum, despite having no obvious clinical sign of infection. Previously, the patient had undergone four iterative femoral surgeries following a road traffic accident which occurred 20 years before. During its last surgery for pseudarthrosis, no clinical or biological signs of infection were present. Per operative samples tested positive for S. apiospermum. The patient was successfully treated with oral voriconazole during 6 months with an excellent tolerance. We also provide a review of literature on bone and joint infections due to Scedosporium spp. (S. apiospermum, Scedosporium boydii and Scedosporium aurantiacum), discussing the evolution of their management and outcome which seems to improve since the use of voriconazole.

National epidemiological study reveals longer paediatric bone and joint infection stays for infants and in general hospitals.

AIM: Published studies have suggested that two to five days of intravenous treatment could effectively treat paediatric bone and joint infections (PBJI), allowing a faster discharge. This study analysed the factors associated with PBJI hospital stays lasting longer than five days using the French National Hospital Discharge Database. METHODS: We selected children under 15 years hospitalised in 2013 with haematogenous PBJIs using a validated French algorithm based on specific diagnosis and surgical procedure codes. Risk factors for stays of more than five days were analysed using logistic regression. RESULTS: In 2013, 2717 children were hospitalised for PBJI, with 49% staying more than five days. The overall incidence of 22 per 100 000, was highest in males and toddlers. The main causes were septic arthritis (50%) and osteomyelitis (46%) and 50% of the pathogens were Staphylococci. The odd ratios for stays of five days or more were infancy, coded bacteria and sickle cell disease (7.0), having spondylodiscitis rather than septic arthritis (2.2) and being hospitalised in a general hospital rather than a teaching hospital (1.6). CONCLUSION: Half of the hospital stays exceeded five days, despite scientific evidence supporting a shorter intravenous antibiotherapy regimen. Greater knowledge and widespread use of short treatment regimens are needed.