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Bone and joint infections (BJIs) are difficult to treat and affect a growing number of patients, in which relapses are observed in 10–20% of case. These relapses, which call for prolonged antibiotic treatment and increase resistance emergence risk, may originate from ill-understood adaptation of the pathogen to the host. Here, we investigated 3 pairs of Escherichia coli strains from BJI cases and their relapses to unravel adaptations within patients. Whole-genome comparison presented evidence for positive selection and phenotypic characterization showed that biofilm formation remained unchanged, contrary to what is usually described in such cases. Although virulence was not modified, we identified the loss of 2 virulence factors contributing to immune system evasion in one of the studied strains. Other strategies, including global growth optimization and colicin production, likely allowed the strains to outcompete competitors. This work highlights the variety of strategies allowing in-patient adaptation in BJIs. [ABSTRACT FROM AUTHOR]

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31–7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22–4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis. [ABSTRACT FROM AUTHOR]

Background Daptomycin is increasingly used in the treatment of bone and joint infections (BJIs) and may be responsible for daptomycin-induced eosinophilic pneumonia (DIEP), a potentially severe adverse drug reaction. The aim of this study was to describe DIEP in patients treated at a referral center for the management of BJI, and to revisit current definitions of this disease. Methods Patients treated from 1 January 2012 to 31 March 2021 were included in a prospective cohort (NCT02817711), in which all potential serious adverse events are prospectively recorded. Patients diagnosed with DIEP were retrospectively analyzed using different definitions. Results In a total of 4664 patients included in the cohort during the study period, 1021 patients (21.9%) received daptomycin, of whom 17 (1.7%) were diagnosed with DIEP. Most patients were male (n = 11 [64.7%]), and periprosthetic joint infection was the commonest BJI (n = 12 [70.6%]). Only 1 patient had bronchoalveolar lavage (BAL) eosinophil count ≥25%, while most patients had peripheral blood eosinophilia (n = 15 [88.2%]). Chest computed tomography (CT) was compatible with eosinophilic pneumonia in 13 of 14 cases (92.9%). All patients recovered upon discontinuation of daptomycin. Using the different definitions available, only a minority of cases fulfilled existing criteria for DIEP. We propose a new algorithm that includes specific CT scan signs, and systemic instead of BAL eosinophilia. Conclusions DIEP is a rare event that requires prompt discontinuation of the causative antibiotic. Current criteria to diagnose definite DIEP are too restrictive and not easily applicable in clinical practice. A new algorithm is proposed here (Lyon algorithm) to facilitate the early identification of DIEP. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs). Methods: We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit. Results: Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n = 7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis. Conclusion: In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31–7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22–4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

Bone and Joint Infections (BJI) are medically important, costly and occur in native and prosthetic joints. Arthroplasties will increase significantly in absolute numbers over time as well as the incidence of Prosthetic Joint Infections (PJI). Diagnosis of BJI and PJI is sub-optimal. The available diagnostic tests have variable effectiveness, are often below standard in sensitivity and/or specificity, and carry significant contamination risks during the collection of clinical samples. Improvement of diagnostics is urgently needed. We provide a narrative review on current and future diagnostic microbiology technologies. Pathogen identification, antibiotic resistance detection, and assessment of the epidemiology of infections via bacterial typing are considered useful for improved patient management. We confirm the continuing importance of culture methods and successful introduction of molecular, mass spectrometry-mediated and next-generation genome sequencing technologies. The diagnostic algorithms for BJI must be better defined, especially in the context of diversity of both disease phenotypes and clinical specimens rendered available. Whether interventions in BJI or PJI are surgical or chemo-therapeutic (antibiotics and bacteriophages included), prior sensitive and specific pathogen detection remains a therapy-substantiating necessity. Innovative tests for earlier and more sensitive and specific detection of bacterial pathogens in BJI are urgently needed. [ABSTRACT FROM AUTHOR]

Since the 1970s, outpatient parenteral antimicrobial therapy (OPAT) has been a viable option for patients who require intravenous antibiotics when hospitalization is not warranted. While the benefits of OPAT as a measure to improve the efficiency of healthcare delivery (i.e., reduced hospital days) and patient satisfaction are well-documented, OPAT is associated with a number of challenges, including line complications and reliance on daily healthcare interactions in some cases at home or in a clinic. To minimize the continued need for intensive healthcare services in the outpatient setting, there is trend toward patients self-administering antibiotics at home without the presence of healthcare workers, after adequate training. In most cases, patients administer the antibiotics through an established intravenous catheter. While this OPAT practice is becoming more accepted as a standard of care, the potential for line complications still exists. Outpatient subcutaneous antimicrobial therapy (OSCAT) has become an increasingly accepted alternative route of administration of antibiotics to IV by French infectious diseases physicians and geriatricians; however, currently, no antibiotics are approved to be administered subcutaneously. Antibiotics with longer half-lives that are completely absorbed and have a favorable local tolerability profile are ideal candidates for OSCAT and have the potential to maximize the quality and efficiency of parenteral antibiotic delivery in the outpatient setting. The increasing development of wearable, on-body subcutaneous delivery systems make OSCAT even more viable as they increase patient independence while avoiding line complications and potentially removing the need for direct healthcare professional observation.

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., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs)., Methods: We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit., Results: Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n = 7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis., Conclusion: In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since the 1970s, outpatient parenteral antimicrobial therapy (OPAT) has been a viable option for patients who require intravenous antibiotics when hospitalization is not warranted. While the benefits of OPAT as a measure to improve the efficiency of healthcare delivery (i.e., reduced hospital days) and patient satisfaction are well-documented, OPAT is associated with a number of challenges, including line complications and reliance on daily healthcare interactions in some cases at home or in a clinic. To minimize the continued need for intensive healthcare services in the outpatient setting, there is trend toward patients self-administering antibiotics at home without the presence of healthcare workers, after adequate training. In most cases, patients administer the antibiotics through an established intravenous catheter. While this OPAT practice is becoming more accepted as a standard of care, the potential for line complications still exists. Outpatient subcutaneous antimicrobial therapy (OSCAT) has become an increasingly accepted alternative route of administration of antibiotics to IV by French infectious diseases physicians and geriatricians; however, currently, no antibiotics are approved to be administered subcutaneously. Antibiotics with longer half-lives that are completely absorbed and have a favorable local tolerability profile are ideal candidates for OSCAT and have the potential to maximize the quality and efficiency of parenteral antibiotic delivery in the outpatient setting. The increasing development of wearable, on-body subcutaneous delivery systems make OSCAT even more viable as they increase patient independence while avoiding line complications and potentially removing the need for direct healthcare professional observation., Competing Interests: TF received speaker honorarium from scPharmaceuticals. TL served as a consultant for scPharmaceuticals. JG served as an advisory board member for scPharmaceuticals. VT received honoraria and research grants from scPharmaceuticals. JM was SVP of Clinical Development and Medical Affairs for scPharmaceuticals who was developing antibiotics for subcutaneous administration. CR-B received research grant from the French Health authorities (Agence Nationale de Sécurité du Médicament et des produits de santé, ANSM) and SG from the Foundation Innovations en Infectiologie (FINOVI) to perform a prospective study about the pharmacokinetic and safety of subcutaneous antimicrobial therapy in France (Pharmacocinétique et tolérance des antibiotiques administrés par voie sous-cutanée chez le patient âgé de plus de 65 ans; PHASAGE study). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ferry, Lodise, Gallagher, Forestier, Goutelle, Tam, Mohr and Roubaud-Baudron.)

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 .