Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.

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.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR).

BACKGROUND: The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy. OBJECTIVE: Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR. METHODS: We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate. RESULTS: Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients' populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible. CONCLUSION: The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.

Assessment and management of diabetes-related foot infection according to the new International Working Group on the Diabetic Foot guidelines 2023-Multidisciplinary grand rounds.

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.

Standards for the development and methodology of the 2023 IWGDF guidelines.

AIMS: Diabetes-related foot disease is a major source of patient burden and societal costs. Investing in evidence-based international guidelines on diabetes-related foot disease is important to reduce this burden and costs, provided the guidelines are focused on outcomes important to key stakeholders and are evidence-based and properly implemented. MATERIALS AND METHODS: The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2023 updates were made using the Grading of Recommendations Assessment Development and Evaluation evidence-to-decision framework. This concerns formulating relevant clinical questions and important outcomes, conducting systematic reviews of the literature and meta-analyses where appropriate, completing summary of judgement tables, and writing recommendations that are specific, unambiguous and actionable, along with their transparent rationale. RESULTS: We herein describe the development of the 2023 IWGDF Guidelines on the prevention and management of diabetes-related foot disease, which consists of seven chapters, each prepared by a separate working group of international experts. These chapters provide guidelines related to diabetes-related foot disease on prevention; classification of diabetes-related foot ulcer, offloading, peripheral artery disease, infection, wound healing interventions, and active Charcot neuro-osteoarthropathy. Based on these seven guidelines, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field. CONCLUSIONS: We believe that the adoption and implementation of the 2023 IWGDF guidelines by healthcare providers, public health agencies, and policymakers will improve the prevention and management of diabetes-related foot disease, and subsequently reduce the worldwide patient and societal burden caused by this disease.

Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update).

Diabetes-related foot disease results in a major global burden for patients and the healthcare system. The International Working Group on the Diabetic Foot (IWGDF) has been producing evidence-based guidelines on the prevention and management of diabetes-related foot disease since 1999. In 2023, all IWGDF Guidelines have been updated based on systematic reviews of the literature and formulation of recommendations by multidisciplinary experts from all over the world. In addition, a new guideline on acute Charcot neuro-osteoarthropathy was created. In this document, the IWGDF Practical Guidelines, we describe the basic principles of prevention, classification and management of diabetes-related foot disease based on the seven IWGDF Guidelines. We also describe the organisational levels to successfully prevent and treat diabetes-related foot disease according to these principles and provide addenda to assist with foot screening. The information in these practical guidelines is aimed at the global community of healthcare professionals who are involved in the care of persons with diabetes. Many studies around the world support our belief that implementing these prevention and management principles is associated with a decrease in the frequency of diabetes-related lower-extremity amputations. The burden of foot disease and amputations is increasing at a rapid rate, and comparatively more so in middle to lower income countries. These guidelines also assist in defining standards of prevention and care in these countries. In conclusion, we hope that these updated practical guidelines continue to serve as a reference document to aid healthcare providers in reducing the global burden of diabetes-related foot disease.

The unique multidisciplinarity of diabetes-related foot disease.

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.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.

Interventions in the management of diabetes-related foot infections: A systematic review.

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.

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

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.

Diagnosis of infection in the foot of patients with diabetes: A systematic review.

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.

Definitions and criteria for diabetes-related foot disease (IWGDF 2023 update).

Multiple disciplines are involved in the management of diabetes-related foot disease and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetes-related foot disease. This document describes the 2023 update of these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research, to facilitate clear communication with people with diabetes-related foot disease and between professionals around the world.

Dalbavancin as suppressive therapy for implant-related infections: a case series with therapeutic drug monitoring and review of the literature.

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.

Burden of Candida-related vascular graft infection: a nested-case control study.

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.

Outcomes in orthopedic device infections due to Streptococcus agalactiae: a retrospective cohort study.

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.

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

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.

Dalbavancin plasma concentrations in 133 patients: a PK/PD observational study.

OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.

Rifabutin versus rifampicin bactericidal and antibiofilm activities against clinical strains of Staphylococcus spp. isolated from bone and joint infections.

BACKGROUND: Staphylococci account for approximately 60% of periprosthetic joint infections (PJIs). Rifampicin (RMP) combination therapy is generally considered to be the treatment of choice for staphylococcal PJIs but carries an important risk of adverse events and drug-drug interactions. Rifabutin (RFB) shares many of the properties of rifampicin but causes fewer adverse events. OBJECTIVES: To compare the minimal inhibitory concentration (MIC), the minimum bactericidal concentrations (MBC), and the minimum biofilm eradication concentrations (MBEC) of rifabutin and rifampicin for staphylococcal clinical strains isolated from PJIs. METHODS: 132 clinical strains of rifampicin-susceptible staphylococci [51 Staphylococcus aureus (SA), 48 Staphylococcus epidermidis (SE) and 33 other coagulase-negative staphylococci (CoNS)] were studied. The MBC and the MBEC were determined using the MBEC® Assay for rifabutin and rifampicin and were compared. RESULTS: When compared with the rifampicin MIC median value, the rifabutin MIC median value was significantly higher for SA (P < 0.05), but there was no statistically significant difference for SE (P = 0.25) and CoNS (P = 0.29). The rifabutin MBC median value was significantly higher than that of rifampicin for SA (P = 0.003) and was lower for SE (P = 0.003) and CoNS (P = 0.03). Rifabutin MBEC median value was statistically lower than that of rifampicin for all strains tested. CONCLUSIONS: Using the determination of MBEC values, our study suggests that rifabutin is more effective than rifampicin against clinical strains of Staphylococcus spp. obtained from PJIs. Using MBECs instead of MICs seems to be of interest when considering biofilms. In vivo higher efficacy of rifabutin when compared with rifampicin needs to be confirmed.

Conservative surgical treatment for metatarsal osteomyelitis in diabetic foot: experience of two French centres.

AIMS: Conservative surgery (CS) for diabetic foot osteomyelitis (DFO) consists in removing all or part of the infected bone tissues without amputation, in complement with antibiotic therapy. Data on CS for DFO therapy are scarce. MATERIAL AND METHODS: We performed a retrospective analysis of all DFO episodes treated with CS between 06/2007 and 12/2017. Remission was defined by the absence of soft-tissue infection, complete sustained (i.e. > 1 month) healing of the foot ulcer, favourable (i.e., stabilisation or improvement) radiological outcome, and no need for additional surgery during a 1-year follow-up. RESULTS: During the study period, 47 episodes (in 41 patients) were analysed. Excluding deaths (all unrelated to the DFO; n = 3) or loss to follow-up before 1 year (n = 5), the remission rate was 64.2%. Most failures occurred during the first 6 months (79%, 11/14). Patients who experienced failure had a higher rate of peripheral arterial disease with arterial stenosis than patients in remission (57% vs. 24%, P = 0.03), a higher C-reactive protein rate at admission (116 ± 112 mg/L vs. 48 ± 46 mg/L, P = 0.02), and a trend for a higher rate of abscesses (29% vs. 4%, P = 0.06). At 1-year follow-up, foot ulcers related to transfer lesion were identified in 25.5% of the cases. At the last follow-up (mean 3 ± 2 years), the remission rate was 23/25 (92%). CONCLUSIONS: Our results suggest that CS is a therapeutic option in patients with localised but severe DFO. Clinicians should, however, consider the necessity of revascularisation, and higher risk of failure if surgery is performed in patients presenting with acute foot infections.