Eric Senneville

Infections caused by multidrug-resistant Gram-negative (MDR-GN) bacteria, particularly carbapenem-resistant organisms (CROs), constitute a significant burden in critically ill patients (CIPs). A multidisciplinary, collaborative approach is essential for responsible antibiotic use in CIPs, balancing the necessity for effective treatment with mitigation of antimicrobial resistance (AMR). While the efficacy of existing antibiotics against CROs is increasingly limited due to resistance development and suboptimal pharmacokinetic/pharmacodynamic properties, several barriers impede the widespread adoption of new agents, including selective susceptibility testing, limited availability, high costs, and concerns regarding the fostering of resistance. Antimicrobial stewardship (AMS) strategies aim to optimize antibiotic use; however, there is an ongoing debate between restrictive and enabling approaches for new antibiotics in CIPs with CRO infections. While restrictive strategies focus on limiting antibiotic use to mitigate resistance, they may delay necessary treatment and negatively impact professional culture. Enablement strategies promote informed decision-making and accessibility when needed but require substantial workforce and expertise. In this narrative review and expert opinion, we propose an algorithm supporting a coordinated AMS approach in CIPs, emphasizing the importance of early diagnosis and appropriate therapy. We advocate for an enablement strategy for new antibiotics in CIPs with MDR-GN infections, aiming to reduce mortality and toxicity associated with older agents. This strategy should be integrated into local AMS programmes under the guidance of experienced clinicians.

Background: Management of prosthetic joint infections (PJIs) due to Candida spp. remains challenging and poorly standardized. Epidemiological patterns and therapeutic strategies may vary between centers and countries, potentially reflecting differences in access to antifungal agents. Methods: We performed a secondary analysis of an international, multicenter, retrospective study supported by the European Society of Clinical Microbiology and Infectious Diseases, including Candida PJI diagnosed between 2010 and 2020. Cases met European Bone and Joint Infection Society criteria, combining clinical signs of infection with at least 2 intraoperative samples positive for Candida spp. Follow-up was 2 years. Epidemiology, management, and outcomes were compared across 5 groups: France, Spain, England, Austria, and other countries. Results: Overall, 268 cases were included: France (n = 142), Spain (n = 42), England (n = 38), Austria (n = 36), and others (Brazil, Lithuania, Italy; n = 9). Distribution of infected sites was similar across countries (hip 53.4%, knee 43.3%, and other 3.3%), as was species epidemiology (Candida albicans 55.6%, Candida parapsilosis 29.5%, Candida glabrata 7.8%, and Candida tropicalis 5.6%). Surgical strategies differed: 1-stage exchange was more frequent in France (36.0%) and Austria (34.3%), whereas 2-stage exchange predominated in England (42.1%) and Spain (37.2%). Echinocandins were prescribed significantly more often in France (41.8%) than elsewhere. Overall outcomes were poor, with a global failure rate of 43%, without significant differences between countries. Conclusions: International differences in epidemiology and management of Candida PJI appear limited. Variations in surgical and antifungal strategies did not translate into improved outcomes, highlighting the need for optimized and standardized management approaches in future collaborative prospective studies worldwide and clinical.

L’ostéite du pied diabétique (OPD) est une complication survenant à la suite d’une plaie située sous les malléoles chez un patient diabétique. L’OPD survient à la faveur d’une plaie généralement chronique du pied favorisée par la neuropathie e/ou l’artérite des membres inférieurs fréquemment associées au diabète. Il s’agit bien d’une ostéite et non d’une ostéomyélite car l’origine hématogène de l’OPD n’est pratiquement pas décrite. L’OPD est une affection dont l’incidence augmente régulièrement avec l’évolution du diabète dans le monde. On estime en effet que 15 à 25% des patients diabétiques présenteront à un quelconque moment de leur existence une ulcération du pied qui subira une infection dans 40 à 80% des cas. L’OPD retarde la cicatrisation des plaies qui ont conduit à sa survenue et augmente significativement le risque d’amputation mineure ou majeure. C’est, avec l’artérite des membres inférieurs, l’une des grandes causes d’amputation d’un membre inférieur chez les patients diabétiques. L’OPD est avant tout une infection ostéo-articulaire qui survient sur un terrain particulier. L’altération des défenses immunitaires systémiques et locales, quoique variables d’un sujet diabétique à un autre, réduit les chances de guérison de l’OPD. S’agissant d’une infection ostéo-articulaire chronique le plus souvent staphylococcique survenant sur un terrain fragilisé il a longtemps été estimée que la guérison ne pouvait être espérée sans la suppression du tissu ostéo-articulaire infecté, en pratique sans amputation. L’amputation n’est cependant pas sans conséquence fonctionnelle et » l’épargne ostéo-articulaire » a été prônée ces dernières années sous deux formes : la résection ostéo-articulaire suspendue ou « amputation fonctionnelle » et le traitement purement médical faisant appel principalement aux antibiotiques. Le traitement médical de l’OPD a l’avantage de n’entraîner aucune lésion anatomique du pied. Il a l’inconvénient de faire appel à des molécules antibiotiques réputées efficaces dans le contexte particulier d’infection ostéo-articulaire chronique qui ont pour la plupart des molécules un effet de pression de sélection de la résistance bactérienne élevé et pour la plupart un potentiel toxique majoré par les co-morbidités fréquemment observées chez ces patients. En considérant les règles généralement admises pour le traitement des infections ostéo-articulaires, il apparait que le choix des antibiotiques doit idéalement être fondé sur les données de la culture d'un fragment osseux. Ceci représente cependant une approche nouvelle pour le traitement antibiotique de l'OPD. Nous montrerons dans ce travail les résultats de travaux publiés suggérant que:1) la biopsie osseuse transcutanée est une technique dénué de risque et actuellement la seule technique permettant une documentation fiable de l’OPD et que les prélèvements obtenus par écouvillonnage ou par ponction-aspiration ne peuvent être utilisés en remplacement de la biopsie osseuse (articles 1 et 2)2) les patients traités médicalement pour OPD ont plus de chance de guérir lorsque le traitement est fondé sur les résultats d'une biopsie osseuse (article 3) nque sur ceux de prélèvements superficiels3) la biopsie osseuse transcutanée n'est actuellement pratiquement pas utilisée dans la majorité des centres Français du pied diabétique. Enfin, nous présenterons les projets de 3 études sur le sujet de la biopsie osseuse en cours ou qui seront développées dans les mois à venir.

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.

Background: Cefiderocol (CFD) is a novel siderophore cephalosporin developed for the treatment of infections involving multidrug-resistant (MDR) Gram-negative bacilli (GNB) infections (1–3). For bone and joint infections (BJIs), the use of CFD is currently neither part of its market authorization nor recommended, and has not yet been assessed by large-scale studies. Objectives: To fill the scarcity of data regarding the use of CFD in BJIs, we aimed to describe patients’ and infection characteristics along with the outcomes of the infection. Methods: We conducted a retrospective observational multicenter study in 22 French centers from January 2019 to December 2023. Results: From January 2019 to December 2023, 45 patients were included. Patients were mainly males (73%) with a median age of 62 years (interquartile range [IQR] 29), and a median Charlson comorbidity index of 3. Implant-related infections (20) were the most prominent, accounting for 44% of the cases. Carbapenemase-producing GNB were involved in 74% of the cases (n = 17/23), among which Pseudomonas aeruginosa accounted for 38% of these cases. Most patients received 6 g of CFD per day. CFD was used in combination with an antibiotic in 40 out of 45 cases (89%). The median duration of CFD treatment was 34 days. Seven patients (16%) experienced side effects, mainly gastro-intestinal disorders, including three (7%) who induced treatment cessation. Infection control included surgery in 37 (82%) patients. Failures and deaths occurred, respectively, in 22 (49%) and 10 (22%) cases. Conclusions: Our results suggest that CFD may be an alternative in MDR-GNB infections with limited therapeutic options.

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.