Objectives: Periprosthetic joint infections (PJIs) are predominantly caused by gram-positive bacteria. Fluoroquinolones (FQs), combined with rifampicin (RMP), are often used but may be unsuitable due to resistance, side effects, or intolerance. Second-generation tetracyclines (TTCs), such as doxycycline and minocycline, show promise as alternatives. This study compared the efficacy and tolerance of RMP-FQ versus RMP-TTC combinations in PJI treatment. Methods: A retrospective study at Tourcoing Hospital, France, reviewed staphylococcal- and streptococcal-related PJI cases treated with RMP-FQ or RMP-TTC from 2013 to 2021. Patients were followed up for 2 years. A Cox regression analysis was used to compare risk of failure. A propensity score using inverse probability of treatment weighting (IPTW) was performed to balance covariates. Results: Of 105 patients, 70 received RMP-FQ and 35 RMP-TTC. Infections were mainly monomicrobial (80 %). IPTW-adjusted Cox regression revealed no significant difference in treatment failure between the RMP-FQ and RMP-TTC groups (aHR 0.68; 95 % CI = 0.32-1.4). Subgroup analyses suggested no difference for infections caused by S. aureus (HR 1.1; CI 95 % = 0.3-4.0) or coagulase-negative staphylococci (CoNS) (HR 0.54; 95 % CI = 0.1-2.1). Adverse events were similar in both groups (20 % vs. 19 %, p > 0.9 ). Conclusions: RMP-TTC therapy could be considered a potential therapeutic option for PJIs when FQs cannot be used.

BACKGROUND:Dalbavancin is a promising option for the treatment of complex gram-positive infections. However, the optimal dosing regimen to ensure adequate drug exposure during prolonged treatment courses remains debate. OBJECTIVES:To evaluate whether an intravenous dalbavancin regimen of 1500 mg administered on days 1, 15 and 43 achieves validated serum concentration targets for infections requiring 12 weeks of treatment. METHODS:We conducted a retrospective bicentric study including patients who received three 1500 mg doses of dalbavancin intended to provide 12 weeks of treatment coverage between January 2020 and May 2024. Patients' characteristics, microbiological data, and dalbavancin concentrations measured before reinjection on days 15, 43 and 90 were collected. We targeted a total dalbavancin plasma concentration of ≥8.04 mg/L, validated for Staphylococcus spp. strains with a MIC ≤0.125 mg/L. Concentrations were compared according to body mass index (≥30 kg/m2) and albumin level (≥30 g/L). RESULTS:Forty-two patients (39 bone and joint infections and three vascular infections) were included. Dalbavancin serum trough concentrations exceeded 8.04 mg/L for all available measurements (76/76) across the different monitored time points during the 12-week treatment period. Although lower concentrations were observed in patients with hypoalbuminemia or obesity, all measured values remained above the target threshold. CONCLUSIONS:These results suggest that a three-dose dalbavancin regimen administered on days 1, 15, and 43 may achieve validated pharmacokinetic targets and maintain therapeutic exposure over a 12-week period for staphylococcal infections with a dalbavancin MIC ≤0.125 mg/L. Therapeutic drug monitoring should be performed for patients with hypoalbuminemia or obesity until larger studies confirm these findings, and for strains with an MIC >0.125 mg/L.

To validate a day 1, 15, and 43 intravenous dalbavancin regimen for infections requiring 12 weeks of treatment by measuring dalbavancin serum concentrations. We conducted a bicentric study of patients who received three injections of dalbavancin at 1,500 mg to cover a 12-week treatment between January 2020 and May 2024. We collected patient's characteristics, microbiological data, and dalbavancin concentrations before reinjection on Days 15 and 43, and at 12 weeks. The target attainment of total dalbavancin concentration was 8.04 mg/L over time. Concentrations in patients with a body mass index greater than or lesser than 30 kg/m² and with albumin levels greater than or less than 30 g/L were compared. Forty-two patients with 39 bone and joint infections and three vascular infections were included. Dalbavancin serum concentrations were above 8.04 mg/L for 100% of the measurements (76/76), including patients with hypoalbuminemia or obesity, noting that non-significant lower concentrations were recorded in obese versus non-obese patients. Our results suggest that dalbavancin 3-dose regimen (day 1,15, and 43) allows covering a three-month antibiotic treatment period. Drug monitoring for patients with hypoalbuminemia or obesity should be performed until larger studies confirm these findings.

Diabetic foot ulcers can progress to diabetic foot osteomyelitis (DFO). Intravenous (IV) antibiotics are traditionally the standard treatment for DFO, but it might reduce quality of life, increase adverse events and costs. Our objective was to examine the potential advantages and disadvantages of antibiotic administration routes for DFO to support a future patient decision aid tool. We conducted a scoping review using the Joanna Briggs Institute methodological framework to map evidence on antibiotic administration routes for DFO using the quintuple aim for quality of care. Records from databases, reference lists, and grey literature were deduplication in EndNote, screened in Rayyan, and assessed independently by two interdisciplinary reviewers. Of 6814, 25 studies were included, all quantitative and mainly retrospective observational (76 %). The majority (68 %) included adult patients with diabetic foot infection or DFO. Oral and IV antibiotics demonstrated comparable clinical outcomes across studies. Data on patient-reported outcomes and experience, team management, equity factors, and standardized definitions of clinical endpoints were largely scarce across studies. Current data suggest that oral antibiotic therapy may be a safe and effective alternative to IV therapy in selected patients with DFO, though substantial evidence gaps remain beyond infection management.

Introduction: Osteomyelitis is a severe complication of diabetes-related foot ulcers (DFUs) often managed with antibiotic therapy and surgical resection of the infected bone. Areas of research: While intravenous (IV) antibiotics have been the traditional approach for bone and joint infections in general, randomized clinical trials have shown that, overall, oral antibiotics are non-inferior to IV antibiotics. While comparisons between oral antibiotics are generally lacking, the data suggest that oral antibiotics with high bioavailability and bone penetration ratios should be prioritized for osteomyelitis treatment, including diabetic foot osteomyelitis (DFO). Oral regimens reduce hospital stays, avert catheter-related complications, and decrease treatment costs while improving patient satisfaction and quality of life. Despite these advantages, IV antibiotics remain widely used, partly due to clinical tradition and concerns about oral absorption in individuals with diabetes. Current guidelines recommend transitioning to oral therapy once systemic signs improve, but robust data supporting oral-only regimens for DFO treated non-surgically remain limited. Conclusions: Oral antibiotics represent a safe and effective alternative to IV therapy for many patients with DFO, particularly when high-bioavailability agents are used. Further well-designed studies are needed to validate their efficacy in non-surgical DFO management and inform clinical guidelines.

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

Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52

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.

Background: Anemia is considered a risk factor of severity in systemic sclerosis. Yet, limited data are available on the frequency and causes of anemia in systemic sclerosis. The objectives of our study were to determine the frequency and causes of anemia in systemic sclerosis, to analyze the clinical and biological characteristics of patients with anemia, and to assess the association between anemia and systemic sclerosis prognosis. Methods: We conducted a prospective single-center study from January 2017 to May 2022. Patients underwent a hemoglobin assay and a standardized etiological workup to determine the causes of anemia at the initial visit. Clinical and biological parameters were compared between patients with anemia and those with normal hemoglobin levels. We followed up patients until May 2023 and compared their survival. Results: A total of 502 systemic sclerosis patients, including 107 diffuse cutaneous systemic sclerosis, were included. At enrollment, 100 patients had anemia. The primary cause of anemia was iron deficiency (40%). Among the 32 patients with iron deficiency-associated anemia who underwent gastrointestinal exploration, 56% had digestive bleeding, with upper gastrointestinal tract involvement being the main cause (90%). Patients with anemia at enrollment had higher systemic sclerosis severity scores and more gastrointestinal symptoms compared to patients without anemia (p < 0.05). They exhibited higher systolic pulmonary artery pressure, lower anemia-corrected diffusing capacity for carbon monoxide, and lower forced vital capacity (p < 0.05). During follow-up, 65 patients (14.8%) died. After adjusting for age, systemic sclerosis subtypes, forced vital capacity, and pulmonary arterial hypertension, anemia at inclusion was associated with a higher mortality rate (hazard ratio: 1.94 (95% confidence interval: 1.39–2.48), p = 0.02). Conclusion: Our study shows a high frequency of anemia among patients with systemic sclerosis. Most anemias are due to iron deficiency, and gastrointestinal exploration can identify bleeding in the majority of the cases. In addition, our study confirms that systemic sclerosis patients with anemia have a more severe disease and a higher mortality rate.

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.

The choice of antibiotic regimens for use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected, while their role is reduced but not negligible in the case of surgical options. Some studies have reported the presence of biofilm structures in bone samples taken from patients with diabetic foot osteomyelitis, which raises the question of the place of anti-biofilm antibiotic regimens in this setting. During the last two decades, clinical studies have suggested a potential benefit for anti-biofilm antibiotics, mainly rifampicin against staphylococci and fluoroquinolones against gram-negative bacilli. However, no data from randomized controlled studies have been reported so far. The present work provides a summary of the available data on the question of the place of anti-biofilm antibiotics for the treatment of diabetic foot osteomyelitis, but also the potential limitations of such treatments.

Background: Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Objective: We performed an overview of the diagnostic approaches, follow-up and treatment strategies used in France for the management of SSc-associated ILD (SSc-ILD). Design: Structured nationwide online survey.Methods: A structured nationwide online survey was submitted to participants via the French Medical Societies for Internal Medicine and Pneumology, and research groups on SSc-ILD from May 2018 to June 2020. The 79 multiple-choice and 9 open-ended questions covered the screening of ILD at baseline, monitoring of patients with established SSc-ILD and its management. Fourteen optional vignettes exploring different clinical phenotypes of SSc-ILD were submitted to evaluate therapeutic decisions. Results: All of the 93 participants screened SSc patients for ILD at baseline with 83 (89%) participants relying on a systematic chest computed tomography (CT) scan. Pulmonary function tests (PFT) were prescribed by 87 (94%) participants at baseline and during follow-up. Treatment was started based on abnormal PFT (95%), chest CT scan characteristics (89%), worsening dyspnoea (72%) and drop in SpO 2 during 6-min walk tests (66%). First-line therapy was cyclophosphamide (CYC) (89%), mycophenolate mofetil (MMF) (83%) and prednisone (73%). Rituximab as second-line immunosuppressive therapy (41%) was preferred to antifibrotic agents (18%), and a median daily prednisone dose of 10 mg (interquartile range, 10–15) was prescribed by 73% participants. Extensive SSc-ILD with worsening PFT (95%), regardless of diffusing capacity for carbon monoxide values and skin extension, were more likely to be treated, and CYC was favoured over MMF ( p < 0.01). Extensive SSc-ILD with disease duration of less than 5 years was also a criterium for treatment initiation. Conclusion: This overview of practices in diagnosis, follow-up and treatment of SSc-ILD in France describes real-life management of patients. It highlights heterogeneity in this management and gaps in current strategies that should be addressed to improve and harmonize clinical practices in SSc-ILD.

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.

AbstractObjectivesAssessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot).MethodsOverlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak.ResultsSpecific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies.ConclusionIFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response.