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Les infections ostéoarticulaires (IOA) sont des infections rares mais présentant une morbi-mortalité et un poids économique important. La complexité des IOA découle de leur grande variété de présentation et est responsable d'une hétérogénéité de prise en charge importante. L'identification de facteurs de risques d'échecs à partir de l'analyse des registres préexistants a permis de faire émerger la définition d'IOA complexe. Cette définition a permis de mieux catégoriser ces infections et de cibler celles au pronostic vital et fonctionnel plus grave et responsables d'un coût plus élevé. Afin de proposer une prise en charge homogène et optimale de ces infections, la nécessité d'une expertise pluridisciplinaire s'est imposée et le ministère de la santé (DGOS), soutenu par les sociétés savantes, a mis en place le réseau des Centres de référence des infections ostéoarticulaires (CRIOA) en 2008. Ce réseau s'est développé, comptant actuellement, 9 centres de références et 21 centres correspondants, couvrant tout le territoire. Au sein de ces centres se tiennent des réunions de concertation pluridisciplinaire composées à minima d'infectiologues, de chirurgiens orthopédistes et de microbiologistes, pour répondre aux demandes d'avis spécialisés et organiser le parcours de soins des patients. De plus, ces centres ont une mission de formation à la prise en charge des IOA avec la création d'un diplôme inter-universitaire et l'organisation d'un congrès national centré sur ces infections. Ce réseau a également pour objectif de promouvoir la recherche et le développement technologique par la réalisation d'essais cliniques nationaux et l'analyse des données de RCP consignées au sein d'un registre national. Bone and joint infections (BJI) are rare but have a high morbidity and economic burden. The complexity of these infections is the consequence of their heterogeneous clinical presentation and is responsible for significant heterogeneity in their management. Risk factors for failure were identified based on the analysis of pre-existing registries and led to the emergence of a new definition : Complex-BJI. This definition has allowed a better categorization of these infections and the targeting of those with a more serious vital and functional prognosis and a high economic impact. In order to offer a homogeneous and optimal management of these infections, the need for a multidisciplinary expertise became apparent and the Ministry of Health, supported by the healthcare societies, set up a national network of referral centers for complex bone and joint infections in 2008. These centers have been implemented sequentially throughout the French territory and, currently, 9 reference centers and 21 associate centers were certified. Their role are: 1) to provide advice on the management of BJI at a local and regional level and especially for Complex-BJI through periodic multidisciplinary meetings involving at least an infectious diseases specialist, an orthopedic surgeon and a microbiologist; 2) to organize learning sessions for BJI management with the creation of a postgraduate diploma and the organization of a national scientific meetings focused on these infections; 3) to promote clinical research and technological development by conducting national-wide clinical trials and epidemiological analysis based on the data from multidisciplinary meetings recorded in a national registry. [ABSTRACT FROM AUTHOR]

Les infections ostéoarticulaires sont des infections polymorphes par la variété de sites infectés, la présence de matériel et la chronicité de l'infection. Leur physiopathologie implique des interactions complexes entre agent infectieux, tissu ostéoarticulaire et système immunitaire. Elle met en jeux des facteurs de virulence à la phase aiguë d'invasion et de destruction tissulaire, et des mécanismes de persistance bactérienne menant à la chronicité et aux rechutes. L'infection peut résulter de trois voies : l'inoculation directe au cours d'une procédure invasive ou d'un traumatisme ouvert, l'extension d'un foyer adjacent par contiguïté, ou hématogène au cours d'une bactériémie. S'ensuit l'adhésion au tissu osseux et le développement du foyer infectieux induisant une réponse inflammatoire responsable d'un déséquilibre de l'homéostasie osseuse menant à une stimulation de l'ostéolyse. À l'inverse, les mécanismes de persistance bactérienne permettent un échappement au système immunitaire et à l'action de la plupart des antibiotiques, et incluent : (i) la formation de biofilm, communauté bactérienne adhérée à une surface organisée dans une matrice extracellulaire autoproduite favorisant l'adhésion et permettant de réguler la survie bactérienne face aux différentes agressions, (ii) l'internalisation et la persistance bactérienne au sein des cellules osseuses permettant la formation de réservoirs bactériens intracellulaires, et (iii) l'évolution vers le morphotype de small colony variant caractérisé par un métabolisme ralenti et une sensibilité moindre aux antibiotiques. Bone and joint infections gather heterogeneous clinical situation according to the infected site, the presence of orthopedic device and the infection chronicity. Their pathophysiology implicates complex interactions between the infectious agent, host immune system and osteoarticular tissue. It involves virulence factors at the initial phase of tissue invasion and destruction, and persistence mechanisms leading to chronicity and relapse. Infection can arise from three different pathways: direct inoculation during and invasive procedure or an open trauma, extension of a contiguous infection, or hematogenous spread during a bacteremia. Then, bacteria adhesion and the initial development of infection induces an inflammatory response that unbalances bone homeostasis resulting in bone lysis. Conversely, persistence mechanisms allow bacterial escape from the host immune system and the action of most antimicrobials. They include: (i) biofilm formation, a bacterial community adherent to the osteoarticular tissue and/or orthopedic device and organized in a self-produced matrix, that regulates bacterial survival in hostile growth conditions; (ii) bacterial internalization and persistence within bone cells constituting intracellular reservoirs; and (iii) phenotype switching to small colony variants characterized by a reduced metabolism and a tolerance to antimicrobials. [ABSTRACT FROM AUTHOR]

Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38–3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3–0.94 and HR = 0.65; 95% CI, 0.46–0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27–3.19). The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS. [ABSTRACT FROM AUTHOR]

Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017–18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30–45; range 21–58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak—predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. None. [ABSTRACT FROM AUTHOR]

It has been suggested that the outcomes of coronavirus disease 2019 (COVID-19) are better in individuals having recently received an influenza vaccine than in non-vaccinated individuals. We hypothesized that this association depends on the humoral responses against influenza viruses. We aim to assess the relationship between the humoral immunity against influenza and the 3-month all-cause mortality among hospitalized older patients with COVID-19. We performed an exploratory retrospective study of older patients (aged 65 and over) hospitalized for confirmed COVID-19 between November 2020 and June 2021. Previous humoral responses to influenza viruses were assessed using a hemagglutination inhibition assay on routinely collected blood samples. The study's primary outcome was the 3-month all-cause mortality, and the secondary outcomes were severe COVID-19 (oxygen requirement ≥ 6 L/min or ventilatory support) and complications (kidney or heart failure, thrombosis and bacterial infection). In the cohort of 95 patients with COVID-19, immunity against influenza vaccine subtypes/lineages was not significantly associated with 3-month all-cause mortality, with an OR [95%CI] of 0.22 [0.02–1.95] (p = 0.174) for the H1N1pdm09 subtype, 0.21 [0.03–1.24] (p = 0.081) for A/Hong Kong/2671/2019 H3N2 subtype, 1.98 [0.51–8.24] (p = 0.329) for the B/Victoria lineage, and 1.82 [0.40–8.45] (p = 0.437) for the B/Yamagata lineage. Immunity against influenza vaccine subtypes/lineages was also not significantly associated with severity and complication. Immunity against influenza subtypes/lineages included in the 2020–2021 vaccine was not associated with a lower 3-month all-cause mortality among COVID-19 hospitalized patients. Trial registration: The study was approved by a hospital committee with competency for research not requiring approval by an institutional review board (Tours University Medical Center, Tours, France: reference: 2021_015). All patients give the informed consent. [ABSTRACT FROM AUTHOR]

Objectives. Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. Methods. A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. Results. A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France. [ABSTRACT FROM AUTHOR]