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Susceptibility of delafloxacin on 199 osteoarticular levofloxacin-resistant staphylococci strains was reported in 49% and 1% using SSTI S. aureus breakpoint (0.25 mg/L) and general S. aureus breakpoint (0.016 mg/L) respectively. Fifty percents levofloxacin-resistant staphylococci showed resistance to delafloxacin using CA-SFM/EUCAST recommendations. Microbiological societies should define new breakpoints especially for CoNS.

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BACKGROUND: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. METHODS: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. RESULTS: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). CONCLUSIONS: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

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OBJECTIVES: To identify the current practices with long half-life lipoglycopeptides (LGPs) and potential use/position of oritavancin. RESULTS: Despite their indication being limited to skin and soft tissue infections (SSTIs), long half-life lipoglycopeptides are mainly used off-label to treat bone and joint infections (BJIs) and infective endocarditis. Oritavancin and dalbavancin are both semisynthetic lipoglycopeptide antibiotics with activity against Gram-positive organisms. The game-changing property of these two antibiotics is their one-time dosing. Due to its shorter half-life, oritavancin might have an advantage over dalbavancin for a treatment duration of less than 2 weeks, as it could be used both in prolonged treatments of complicated patients in BJIs or administered as a single-dose treatment for Gram-positive cocci infections usually treated by a 5- to 10-day antibiotic course. These infections include urinary tract infections, bacteremias, catheter-related infections, etc. In addition to the possibility of being used as an end-of-treatment injection, oritavancin could be used as an empiric therapy treatment in the postoperative period in the context of device-associated especially prosthetic joint infections to allow for the early discharge of the patient. METHODS: A qualitative survey was conducted in March 2022 including sixteen infectiologists, one internist, five hospital pharmacists, and one pharmacologist. CONCLUSION: Long half-life lipoglycopeptides contribute to changing the paradigm in the management of acute bacterial infections, as infectiologists now consider a range of indications and patient profiles for one single drug. Oritavancin strengthens the therapeutic arsenal in numerous infections from BJIs to urinary tract infections and could help to manage specific clinical situations, on top of providing potential benefits for the hospital's budget.

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In this Review, we aim to complement the 2023 update of the guidelines of the International Working Group on the Diabetic Foot. We highlight the complexity of the pathological processes that underlie diabetes-related foot ulceration (DFU) and draw attention to the potential implications for clinical management and outcome. Variation observed in the incidence and outcome of DFUs in different communities might result from differences in study populations and the accessibility of care. Comparing differences in incidence, management, and outcome of DFUs in different communities is an essential component of the quality of disease care. Additionally, these comparisons can also highlight the relationship between DFU incidence, management, and outcome and the structure of local clinical services and the availability of staff with the necessary skills. The clinical outcome is, however, also dependent on the availability of multidisciplinary care and the ability of people with DFUs to gain access to that care.

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OBJECTIVES: We aimed to assess the frequency, management, and burden of enterococcal-related vascular graft infection. PATIENTS AND METHODS: From 2008 to 2021, data regarding all episodes of vascular graft infections initially managed or secondarily referred to our referral center were prospectively collected. We described the history and management of the infection, depending on the type of prosthesis used. RESULTS: The frequency of enterococcal-related vascular graft infections was 29/249 (12 %). Most of them were early infections (22/29, 76 %). Infections were polymicrobial (26/29, 90 %), mostly associated with Enterobacterales. Among patients with positive blood cultures, 7/8 (88 %) involved enterococci. Patients with enterococcal-related vascular graft infections were mainly (22/29, 76 %) treated with an association of antibiotics. Mortality and relapse occurred in 28 % and 7 % respectively of the cases. CONCLUSIONS: Enterococcal-related vascular graft infections occurred in patients with comorbidities, during the early period following surgery and were more frequent in cases of intra-cavitary prosthesis. Their potential virulence needs to be considered, especially in polymicrobial infections.

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Implant-related infections may need suppressive antibiotic therapy (SAT). We describe a SAT strategy using dalbavancin with therapeutic drug monitoring (TDM). This is a retrospective bicentric study of patients with implant-related infection who received dalbavancin SAT between January 2021 and September 2023. Fifteen patients were included. Median number of injections was 4 (IQR: 2-7). Median time between two reinjections was 57 days (IQR 28-82). Dalbavancin plasma concentrations were above 4 mg/L for 97.9% of dosages (93/95) and above 8 mg/L for 85% (81/95). These results support the use of dalbavancin SAT for implant-related infections.

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Few diseases globally require treatment from so many different disciplines as diabetes-related foot disease. At least 25 different professionals may be involved: casting technicians, dermatologists, diabetes (educator) nurses, diabetologists, dieticians, endocrinologists, general practitioners, human movement scientists, infectious diseases experts, microbiologists, nuclear medicine physicians, orthopaedic surgeons, orthotists, pedorthists, physical therapists, plastic surgeons, podiatric surgeons, podiatrists, prosthetists, psychologists, radiologists, social workers, tissue viability physicians, vascular surgeons, and wound care nurses. A shared vocabulary and shared treatment goals and recommendations are then essential. The International Working Group on the Diabetic Foot (IWGDF) has produced guidelines and supporting documents to stimulate and support shared and multidisciplinary evidence-based treatment in diabetes-related foot disease. In this special virtual issue of Diabetes/Metabolism Research and Reviews, all 21 documents of the 2023 update of the IWGDF Guidelines are bundled, added with a further 6 reviews from multidisciplinary experts to drive future research and clinical innovations, based on their contributions to the International Symposium on the Diabetic Foot. We hope the readers will enjoy this special virtual issue, and widely implement the knowledge shared here in their daily clinical practice and research endeavours with the goal to improve the care for people with diabetes-related foot disease.

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BACKGROUND: Group B streptococci (Streptococcus agalactiae) (GBS) is a rare cause of prosthetic joint infection (PJI) occurring in patients with comorbidities and seems to be associated with a poor outcome. Depiction of GBS PJI is scarce in the literature. METHODS: A retrospective survey in 2 referral centers for bone joint infections was done Patients with a history of PJI associated with GBS between 2014 and 2019 were included. A descriptive analysis of treatment failure was done. Risk factors of treatment failure were assessed. RESULTS: We included 61 patients. Among them, 41 had monomicrobial (67%) infections. The median duration of follow-up was 2 years (interquartile range 2.35) Hypertension, obesity, and diabetes mellitus were the most reported comorbidities (49%, 50%, and 36% respectively). Death was observed in 6 individuals (10%) during the initial management. The rate of success was 63% (26/41). Removal of the material was not associated with remission (p = 0.5). We did not find a specific antibiotic regimen associated with a better outcome. CONCLUSION: The results show that S. agalactiae PJIs are associated with high rates of comorbidities and a high treatment failure rate with no optimal treatment so far.

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BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

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PURPOSE: We aimed to assess risk factors of candida-related Vascular Graft Infections (VGIs). METHODS: We did a case-control study (1:4) matched by age and year of infection, nested in a cohort of patient with a history of VGIs. Cases were defined by a positive culture for Candida spp. in biological samples and controls were defined by a positive culture for bacterial strains only in biological samples. Risk factors for Candida-related VGIs were investigated using multivariate logistic regression. Mortality were compared using survival analysis. RESULTS: 16 Candida-related VGIs were matched to 64 bacterial-related VGIs. The two groups were comparable regarding medical history and clinical presentation. Candida-related VGIs were associated with bacterial strains in 88% (14/16). Gas/fluid-containing collection on abdominal CT scan and the presence of an aortic endoprosthesis were risk factors for Candida spp.-related VGIs [RRa 10.43 [1.81-60.21] p = 0.009 RRa and 6.46 [1.17-35.73] p = 0.03, respectively]. Candida-related VGIs were associated with a higher mortality when compared to bacterial-related VGIs (p = 0.002). CONCLUSIONS: Candida-related VGIs are severe. Early markers of Candida spp. infection are needed to improve their outcome. The suspicion of aortic endoprosthesis infection may necessitate probabilistic treatment with antifungal agents.

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INTRODUCTION: The GeneXpert® MRSA/SA SSTI (Methicillin Resistant Staphylococcus aureus/S. aureus skin and soft tissue infection) PCR test allows early detection of methicillin resistance in staphylococci. This test was developed for skin infections and has been evaluated for prosthetic joint infections but, to our knowledge, has not been evaluated for hardware infections outside of arthroplasties. Furthermore, we conducted a retrospective study in patients with non-prosthetic osteosynthesis hardware aiming: (1) to identify the diagnostic values of the PCR test compared to conventional cultures and the resulting rate of appropriate antibiotic therapy; (2) to identify the rate of false negative (FN) results; (3) to identify and compare the rates of failure of infectious treatment (FN versus others); (4) to search for risk factors for FN of the PCR test. HYPOTHESIS: The PCR test allowed early and appropriate targeting of antibiotic therapy. MATERIAL AND METHODS: The results of PCR tests and conventional cultures for osteoarticular infections of non-prosthetic hardware over four years (2012-2016) were compared to identify the diagnostic values of using the results of conventional culture as a reference and the rate of appropriate antibiotic therapies. Infectious management failures between the results of the FN group and the others were compared, and variables associated with a FN of the PCR test were identified. RESULTS: The analysis of 419 PCR tests allowed us to establish a sensitivity of 42.86%, a specificity of 96.82%, a positive predictive value of 60% and a negative predictive value of 93.83%. Using the results of the PCR test for the targeting of postoperative antibiotic therapy, it was suitable for staphylococcal coverage in 90.94% (381/419). The rates of patients for whom infectious treatment failed were not significantly different between the FN group and the other patients (20.8% versus 17.7%, respectively; Hazard Ratio=1.12 (95%CI 0.47-2.69, p=0.79)). A skin opening during the initial trauma (p=0.005) and a polymicrobial infection were significantly associated with a risk of FN from the PCR test (p<0.001). CONCLUSION: The PCR test makes it possible to reduce the duration of empirical broad-spectrum antibiotic therapy during the treatment of an infection of osteosynthesis hardware but causes a lack of antibiotic coverage in 9.06% of cases. LEVEL OF EVIDENCE: III; diagnostic case control study.

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The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

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BACKGROUND: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers. RESULTS: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible. CONCLUSIONS: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality.

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The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

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Foot disease is a devastating complication of diabetes. For almost 3 decades, the mission of the International Working Group on the Diabetic Foot (IWGDF) is to produce evidence-based guidelines to inform health care providers worldwide on strategies for the prevention and management of diabetes-related foot disease. In this publication, we aim to better inform the reader about 'the story behind' the IWGDF Guidelines and thus facilitate improved uptake of the recommendations described in the guidelines. The first IWGDF Guidelines were published in 1999, and these have been successfully updated every 4 years since. With each update, IWGDF has improved the methodological rigour and extended the topics covered. This has been possible thanks to the involvement of > 100 experts from > 60 countries, all voluntarily dedicating their time. We estimate that the 2023 update of the IWGDF Guidelines required a total 10 years of full-time work, which would have cost 2 million euros if the voluntary work had been financially compensated. The IWGDF Guidelines are not only published in English but also translated to support local implementation. Currently available translations serve 2.9 billion people globally in their native language. As an independent and multidisciplinary organisation, IWGDF hopes that the 2023 update will continue to stimulate clinicians from all different disciplines to deliver the best care possible for these patients, will motivate researchers to undertake the high-quality trials needed to deliver the new evidence to advance the field further, and collectively will support people with diabetes-related foot disease to minimize their disease burdens.

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OBJECTIVES: We aimed to describe the efficacy and safety of dalbavancin in treatment of patients with diabetes-related foot osteomyelitis with bone culture confirmation. PATIENTS AND METHODS: Between January 2019 and December 2021, all consecutive patients receiving at least one 1500 mg dose of dalbavancin for diabetes-related foot osteomyelitis were included in a retrospective study. Remission was defined as absence of relapsing infection or need for surgery at the initial or a contiguous site during 6-month follow-up from the last dose of dalbavancin. RESULTS: Thirteen patients were included. Eleven (85%) patients were surgically treated. Six (46%) patients received dalbavancin as first-line treatment and 7 (54%) as second-line treatment due to adverse events related to previous treatments. One adverse event was reported. At 6-month follow-up, 11 patients were evaluable and 9 (82%) were in remission. CONCLUSIONS: In the study, dalbavancin was well-tolerated and showed microbiological and clinical efficacy.

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Septic bursitis (SB) is a common condition accounting for one third of all cases of inflammatory bursitis. It is often related to professional activities. Management is heterogeneous and either ambulatory or hospital-based, with no recommendations available. This article presents recommendations for managing patients with septic bursitis gathered by 18 rheumatologists from the French Society for Rheumatology work group on bone and joint infections, 1 infectious diseases specialist, 2 orthopedic surgeons, 1 general practitioner and 1 emergency physician. This group used a literature review and expert opinions to establish 3 general principles and 11 recommendations for managing olecranon and prepatellar SB. The French Health authority (Haute Autorité de santé [HAS]) methodology was used for these recommendations. Designed for rheumatologists, general practitioners, emergency physicians and orthopedic surgeons, they focus on the use of biological tests and imaging in both outpatient and inpatient management. Antibiotic treatment options (drugs and duration) are proposed for both treatment modalities. Finally, surgical indications, non-drug treatments and prevention are covered by specific recommendations.

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Diabetes-related foot disease is a serious and common complication for people with diabetes mellitus. The gold standard care for a person with diabetes-related foot disease is the involvement of a multidisciplinary foot team engaged in evidence-based care. To date, there are seven International Working Group on the Diabetic Foot (IWGDF) guidelines published to assist healthcare providers in managing diabetes-related foot disease around the world. This review discusses the acute management of diabetes-related foot infection with insights from experts of various specialities (internal medicine, infectious disease, vascular surgery, radiology) with a discussion on the implementation of IWGDF guidelines in real life practice and the challenges that healthcare providers may face.

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